@article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/107308, title ="A Covalent p97/VCP ATPase Inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells", author = "Zhang, Gang and Li, Shan", journal = "European Journal of Medicinal Chemistry", month = "January", year = "2021", doi = "10.1016/j.ejmech.2020.113148", issn = "0223-5234", url = "https://resolver.caltech.edu/CaltechAUTHORS:20210104-164231600", note = "© 2021 Elsevier Masson SAS. \n\nReceived 22 November 2020, Revised 16 December 2020, Accepted 28 December 2020, Available online 2 January 2021. \n\nWe thank M. S. Cohen, J. Taunton, and K. Shokat for providing compounds 4,5,6, M. Smythe and C. Crews for YU101, A. M. Weissman for PYR-41, C. C. Wu for β-nitrostyrene analogues (compounds 7, 9,10,11,12), Y. Ye at NIDDK/NIH for providing yeast Cdc48 and hamster NSF plasmids. A.C.J. was supported by NIH Grant F32GM082000; A.F.G.G thanks the Natural Sciences and Engineering Research Council (NSERC) of Canada for a PGS D scholarship; R.J.D. was an HHMI Investigator, and this work was funded in part by HHMI; This work was funded in part by the NIH-NINDS (R01NS100815) to T.F.C. and NIH-NIGMS (R01GM080269) to B.M.S. We thank the anonymous reviewers for constructive criticism. \n\nAuthor contributions\nGang Zhang wrote the manuscript and analyzed the potential interaction between PPA and p97 by molecular docking. Shan Li and Feng Wang performed the anti-proliferative assay and proteomics study. Amanda C. Jones, Alexander F. G. Goldberg, and Scott Virgil synthesized and characterized the target compounds. Tsui-Fen Chou performed experiments in Table 1, Table 2, Table 3, Table 4; Figures 2 and 4. Amanda C. Jones, Brian M. Stoltz, Raymond J. Deshaies, and Tsui-Fen Chou conceived the project and made the major contribution in the design of the initial work. \n\nThe authors have no conflicts of interest to declare.", revision_no = "10", abstract = "Small-molecule inhibitors of p97 are useful tools to study p97 function. Human p97 is an important AAA ATPase due to its diverse cellular functions and implication in mediating the turnover of proteins involved in tumorigenesis and virus infections. Multiple p97 inhibitors identified from previous high-throughput screening studies are thiol-reactive compounds targeting Cys522 in the D2 ATP-binding domain. Thus, these findings suggest a potential strategy to develop covalent p97 inhibitors. We first used purified p97 to assay several known covalent kinase inhibitors to determine if they can inhibit ATPase activity. We evaluated their selectivity using our dual reporter cells that can distinguish p97 dependent and independent degradation. We selected a β-nitrostyrene scaffold to further study the structure-activity relationship. In addition, we used p97 structures to design and synthesize analogues of pyrazolo[3,4-d]pyrimidine (PP). We incorporated electrophiles into a PP-like compound 17 (4-amino-1-tert-butyl-3-phenyl pyrazolo[3,4-d]pyrimidine) to generate eight compounds. A selective compound 18 (N-(1-(tert-butyl)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)acrylamide, PPA) exhibited excellent selectivity in an in vitro ATPase activity assay: IC₅₀ of 0.6 μM, 300 μM, and 100 μM for wild type p97, yeast Cdc48, and N-ethylmaleimide sensitive factor (NSF), respectively. To further examine the importance of Cys522 on the active site pocket during PPA inhibition, C522A and C522T mutants of p97 were purified and shown to increase IC50 values by 100-fold, whereas replacement of Thr532 of yeast Cdc48 with Cysteine decreased the IC₅₀ by 10-fold. The molecular modeling suggested the hydrogen bonds and hydrophobic interactions in addition to the covalent bonding at Cys522 between WT-p97 and PPA. Furthermore, tandem mass spectrometry confirmed formation of a covalent bond between Cys522 and PPA. An anti-proliferation assay indicated that the proliferation of HCT116, HeLa, and RPMI8226 was inhibited by PPA with IC₅₀ of 2.7 μM, 6.1 μM, and 3.4 μM, respectively. In addition, PPA is able to inhibit proliferation of two HCT116 cell lines that are resistant to CB-5083 and NMS-873, respectively. Proteomic analysis of PPA-treated HCT116 revealed Gene Ontology enrichment of known p97 functional pathways such as the protein ubiquitination and the ER to Golgi transport vesicle membrane. In conclusion, we have identified and characterized PPA as a selective covalent p97 inhibitor, which will allow future exploration to improve the potency of p97 inhibitors with different mechanisms of action.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/106432, title ="Global Diastereoconvergence in the Ireland–Claisen Rearrangement of Isomeric Enolates: Synthesis of Tetrasubstituted α-Amino Acids", author = "Fulton, Tyler J. and Cusumano, Alexander Q.", journal = "Journal of the American Chemical Society", volume = "142", number = "52", pages = "21938-21947", month = "December", year = "2020", doi = "10.1021/jacs.0c11480", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20201104-135041447", note = "© 2020 American Chemical Society. \n\nReceived: November 1, 2020; Published: December 15, 2020. \n\nWe thank the NIH-NIGMS (R01GM080269), NSF Grant CHE-1764328, the Gordon and Betty Moore Foundation, and Caltech for financial support. We thank the Caltech High Performance Computing Center for support. E.J.A. thanks the National Science Foundation for a predoctoral fellowship. We thank Dr. David VanderVelde (Caltech) for NMR expertise. Dr. Scott Virgil (Caltech Center for Catalysis and Chemical Synthesis) is thanked for instrumentation and SFC assistance. Dr. Michael Takase (Caltech) and Lawrence Henling (Caltech) are acknowledged for X-ray analysis. We acknowledge the X-ray Crystallography Facility in the Beckman Institute at Caltech and a Dow Next Generation Instrumentation Grant. Alexandra Beard (Caltech) is acknowledged for initial studies on phthalimide removal strategies. This manuscript is dedicated to our friend and colleague Professor Michael Krout (Bucknell University). \n\nAuthor Contributions: T.J.F. and A.Q.C. contributed equally. \n\nThe authors declare no competing financial interest.", revision_no = "41", abstract = "A dual experimental/theoretical investigation of the Ireland–Claisen rearrangement of tetrasubstituted α-phthalimido ester enolates to afford α-tetrasubstituted, β-trisubstituted α-amino acids (generally >20:1 dr) is described. For trans allylic olefins, the Z- and E-enol ethers proceed through chair and boat transition states, respectively. For cis allylic olefins, the trend is reversed. As a result, the diastereochemical outcome of the reaction is preserved regardless of the geometry of the enolate or the accompanying allylic olefin. We term this unique convergence of all possible olefin isomers global diastereoconvergence. This reaction manifold circumvents limitations in present-day technologies for the stereoselective enolization of α,α-disubstituted allyl esters. Density functional theory paired with state-of-the-art local coupled-cluster theory (DLPNO-CCSD(T)) was employed for the accurate determination of quantum mechanical energies.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/99664, title ="Synthesis of non-natural cyanthiwigin–gagunin hybrids through late-stage diversification of the cyanthiwigin natural product core", author = "Kim, Kelly E. and Sakazaki, Yuka", journal = "Tetrahedron", volume = "76", number = "51", pages = "Art. No. 130755", month = "December", year = "2020", doi = "10.1016/j.tet.2019.130755", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20191105-093732898", note = "© 2019 Elsevier Ltd. \n\nReceived 21 September 2019, Revised 26 October 2019, Accepted 28 October 2019, Available online 1 November 2019. \n\nThis work was supported by the NSF under the CCI Center for Selective C–H Functionalization (CCHF), CHE-1700982. Additional financial support was provided by Caltech and Novartis. Dr. David Horne and Dr. Sangkil Nam (City of Hope) are acknowledged for assistance with biological studies. Dr. David VanderVelde, Dr. Mona Shahgholi, and Naseem Torian are acknowledged for assistance with structural determination and characterization.", revision_no = "21", abstract = "Derivitization of natural product scaffolds produces diversely functionalized molecules for biological study and offers insight into the reactivities of complex molecular architectures. In the present study, the tricyclic framework of the cyanthiwigin natural product family was employed as a platform for late-stage diversification. The design and synthesis of several non-natural “hybrid” molecules resembling both the cyanthiwigin and gagunin natural products was accomplished, and the results of these investigations are described herein.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/106642, title ="Recent Advances in Homogeneous Catalysts for the Asymmetric Hydrogenation of Heteroarenes", author = "Kim, Alexia N. and Stoltz, Brian M.", journal = "ACS Catalysis", volume = "10", number = "23", pages = "13834-13851", month = "December", year = "2020", doi = "10.1021/acscatal.0c03958", issn = "2155-5435", url = "https://resolver.caltech.edu/CaltechAUTHORS:20201112-103611899", note = "© 2020 American Chemical Society. \n\nReceived: September 9, 2020; Revised: October 15, 2020; Published: November 12, 2020. \n\nWe thank NIH-NIGMS (R01GM127972A) and Caltech for funding and the support of our research program. \n\nThe authors declare no competing financial interest.", revision_no = "15", abstract = "The asymmetric hydrogenation of heteroarenes has recently emerged as an effective strategy for the direct access to enantioenriched, saturated heterocycles. Although several homogeneous catalyst systems have been extensively developed for the hydrogenation of heteroarenes with high levels of chemo- and stereoselectivity, the development of mild conditions that allow for efficient and stereoselective hydrogenation of a broad range of substrates remains a challenge. This Perspective highlights recent advances in homogeneous catalysis of heteroarene hydrogenation as inspiration for the further development of asymmetric hydrogenation catalysts, and addresses underdeveloped areas and limitations of the current technology.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/106327, title ="Transition Metal Catalyzed [π2s + π2s + σ2s + σ2s] Pericyclic Reaction: Woodward–Hoffmann Rules, Aromaticity, and Electron Flow", author = "Cusumano, Alexander Q. and Goddard, William A., III", journal = "Journal of the American Chemical Society", volume = "142", number = "45", pages = "19033-19039", month = "November", year = "2020", doi = "10.1021/jacs.0c09575", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20201028-103039420", note = "© 2020 American Chemical Society. \n\nReceived: September 6, 2020; Published: October 27, 2020. \n\nWe thank Professor Kendall Houk (UCLA) for insightful discussion. The Caltech High Performance Computing (HPC) center is acknowledged for support of computational resources. We thank the NIH (R01 GM080269), NSF (CBET-1805022), NSF (CBET-2005250), and Caltech for financial support. \n\nThe authors declare no competing financial interest.", revision_no = "24", abstract = "We have shown that the fundamental step responsible for enantioinduction in the inner-sphere asymmetric Tsuji allylic alkylation is C–C bond formation through a seven-membered pericyclic transition state. We employ an extensive series of quantum mechanics (QM) calculations to delineate how the electronic structure of the Pd-catalyzed C–C bond forming process controls the reaction. Phase inversion introduced by d orbitals renders the Pd-catalyzed [π2s + π2s + σ2s + σ2s] reaction symmetry-allowed in the ground state, proceeding through a transition state with Craig–Möbius-like σ-aromaticity. Lastly, we connect QM to fundamental valence bonding concepts by deriving an ab initio “arrow-pushing” mechanism that describes the flow of electron density through the reaction.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/105551, title ="Enantioselective synthesis of highly oxygenated acyclic quaternary center-containing building blocks via palladium-catalyzed decarboxylative allylic alkylation of cyclic siloxyketones", author = "Ngamnithiporn, Aurapat and Iwayama, Toshihiko", journal = "Chemical Science", volume = "11", number = "40", pages = "11068-11071", month = "October", year = "2020", doi = "10.1039/d0sc04383d", issn = "2041-6520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200925-104734427", note = "This journal is © The Royal Society of Chemistry 2020. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. \n\nReceived 9th August 2020. Accepted 10th September 2020. \n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for support of our research program. A. N. thanks the Royal Thai Government Scholarship program. T. I. thanks Japan Tobacco Inc. for funding. We thank Dr Makoto Shiozaki for helpful discussion and Dr Mona Shahgholi for mass spectrometry assistant. Dr Scott Virgil is acknowledged for instrumentation and SFC assistance. \n\nA. N. and T. I. contributed equally to this work. \n\nAll publication charges for this article have been paid for by the Royal Society of Chemistry.", revision_no = "39", abstract = "The development of a palladium-catalyzed enantioselective decarboxylative allylic alkylation of cyclic siloxyketones to produce enantioenriched silicon-tethered heterocycles is reported. The reaction proceeds smoothly to provide products bearing a quaternary stereocenter in excellent yields (up to 91% yield) with high levels of enantioselectivity (up to 94% ee). We further utilized the unique reactivity of the siloxy functionality to access chiral, highly oxygenated acyclic quaternary building blocks. In addition, we subsequently demonstrated the utility of these compounds through the synthesis of a lactone bearing vicinal quaternary-trisubstituted stereocenters.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/101714, title ="Enantioselective Total Synthesis of (–)-Myrifabral A and B", author = "Fulton, Tyler J. and Chen, Anthony Y.", journal = "Chemical Science", volume = "11", number = "39", pages = "10802-10806", month = "October", year = "2020", doi = "10.1039/d0sc01141j", issn = "2041-6520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200304-153439734", note = "© 2020 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. \n\nAll publication charges for this article have been paid for by the Royal Society of Chemistry. \n\nSubmitted 26 Feb 2020; Accepted 20 Apr 2020; First published 21 Apr 2020. \n\nWe thank NIH-NIGMS (R01GM080269) and Caltech for financial support. Dr Scott Virgil (Caltech) is thanked for instrumentation and SFC assistance. We thank Dr David Vander Velde (Caltech) for NMR expertise, and Dr Mona Shahgholi (Caltech) and Naseem Torian (Caltech) for mass spectrometry assistance. \n\nThere are no conflicts to declare.", revision_no = "31", abstract = "A catalytic enantioselective approach to the Myrioneuron alkaloids (−)-myrifabral A and (−)-myrifabral B is described. The synthesis was enabled by a palladium-catalyzed enantioselective allylic alkylation, that generates the C(10) all-carbon quaternary center. A key N-acyl iminium ion cyclization forged the cyclohexane fused tricyclic core, while vinyl boronate cross metathesis and oxidation afforded the lactol ring of (−)-myrifabral A. Adaptation of previously reported conditions allowed for the conversion of (−)-myrifabral A to (−)-myrifabral B.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/105043, title ="Synthesis of Carboxylic Acid and Dimer Ester Surrogates to Constrain the Abundance and Distribution of Molecular Products in α-Pinene and β-Pinene Secondary Organic Aerosol", author = "Kenseth, Christopher M. and Hafeman, Nicholas J.", journal = "Environmental Science and Technology", volume = "54", number = "20", pages = "12829-12839", month = "October", year = "2020", doi = "10.1021/acs.est.0c01566", issn = "0013-936X", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200819-162804852", note = "© 2020 American Chemical Society. \n\nReceived: March 13, 2020; Revised: August 5, 2020; Accepted: August 19, 2020; Published: August 19, 2020. \n\nWe thank John Crounse and Paul Wennberg for useful discussions. UPLC/(−)ESI-Q-TOF-MS was performed in the Caltech Environmental Analysis Center (EAC). This work was supported by National Science Foundation Grants AGS-1523500, CHE-1800511, and CHE-1905340. The EAC is supported by the Linde Center and Beckman Institute at Caltech. \n\nAuthor Contributions: C.M.K. designed research; C.M.K. and Y.H. performed research; C.M.K., N.J.H., and B.M.S. contributed new reagents; C.M.K., Y.H., and N.F.D. analyzed data; and C.M.K. and J.H.S. wrote the paper. \n\nThe authors declare no competing financial interest. \n\nEditor’s Note: This manuscript was selected for a C. Ellen Gonter Environmental Chemistry Award from the ACS Division of Environmental Chemistry.", revision_no = "19", abstract = "Liquid chromatography/negative electrospray ionization mass spectrometry [LC/(−)ESI-MS] is routinely employed to characterize the identity and abundance of molecular products in secondary organic aerosol (SOA) derived from monoterpene oxidation. Due to a lack of authentic standards, however, commercial terpenoic acids (e.g., cis-pinonic acid) are typically used as surrogates to quantify both monomeric and dimeric SOA constituents. Here, we synthesize a series of enantiopure, pinene-derived carboxylic acid and dimer ester homologues. We find that the (−)ESI efficiencies of the dimer esters are 19–36 times higher than that of cis-pinonic acid, demonstrating that the mass contribution of dimers to monoterpene SOA has been significantly overestimated in past studies. Using the measured (−)ESI efficiencies of the carboxylic acids and dimer esters as more representative surrogates, we determine that molecular products measureable by LC/(−)ESI-MS account for only 21.8 ± 2.6% and 18.9 ± 3.2% of the mass of SOA formed from ozonolysis of α-pinene and β-pinene, respectively. The 28–36 identified monomers (C₇₋₁₀H₁₀₋₁₈O₃₋₆) constitute 15.6–20.5% of total SOA mass, whereas only 1.3–3.3% of the SOA mass is attributable to the 46–62 identified dimers (C₁₅₋₁₉H₂₄₋₃₂O₄₋₁₁). The distribution of identified α-pinene and β-pinene SOA molecular products is examined as a function of carbon number (n_C), average carbon oxidation state (OS_C), and volatility (C*). The observed order-of-magnitude difference in (−)ESI efficiency between monomers and dimers is expected to be broadly applicable to other biogenic and anthropogenic SOA systems analyzed via (−) or (+) LC/ESI-MS under various LC conditions, and demonstrates that the use of unrepresentative surrogates can lead to substantial systematic errors in quantitative LC/ESI-MS analyses of SOA.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/105352, title ="Efficient Synthesis of Geminal-Dialkyl Dienes for Olefin Metathesis Polymerization", author = "Wolf, William J. and Li, Jiaming", journal = "Macromolecules", volume = "53", number = "18", pages = "7803-7809", month = "September", year = "2020", doi = "10.1021/acs.macromol.0c01606", issn = "0024-9297", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200911-133138265", note = "© 2020 American Chemical Society. \n\nReceived: July 13, 2020; Revised: August 25, 2020; Published: September 10, 2020. \n\nW.J.W. gratefully acknowledges the support of the Arnold O. Beckman postdoctoral fellowship. B.M.S. thanks the NIH-GMS (R01GM080269) for generous support. We thank Mr. Doug Rose and Prof. Heather Maynard (UCLA) for use of their DSC instrument, and Prof. Marc Hillmyer (UMN) for sharing the details of the synthesis of 38. We are grateful to Steve Cohen and Elevance Renewable Sciences for their donation of methyl 9-decenoate. \n\nAuthor Contributions. W.J.W. and J. L. contributed equally. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. \n\nThe authors declare the following competing financial interest(s): A provisional patent regarding this work (CIT-8317-P) has been filed.", revision_no = "19", abstract = "A robust synthesis of gem-dialkyl acyclic diene monomers has been developed. This route is scalable, flexible, and biorenewable, allowing for the production of a wide range of diene monomers of different lengths and different gem-dialkyl substitutions starting from unsaturated esters derived from seed oils. The metathesis polymerization of these monomers and the hydrogenation of the resulting polyolefins lead to telechelic gem-dialkyl polyethylenes, which can be used as elastomers in the synthesis of polyurethanes and other block polymers.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/104322, title ="Reaction Mechanism, Origins of Enantioselectivity, and Reactivity Trends in Asymmetric Allylic Alkylation: A Comprehensive Quantum Mechanics Investigation of a C(sp³)–C(sp³) Cross-Coupling", author = "Cusumano, Alexander Q. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "142", number = "32", pages = "13917-13933", month = "August", year = "2020", doi = "10.1021/jacs.0c06243", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200710-102850852", note = "© 2020 American Chemical Society. \n\nReceived: June 9, 2020; Published: July 8, 2020. \n\nWe thank the NIH (R01 GM080269) and Caltech for financial support. We further thank Dr. Michael Bartberger (1200 Pharma) for insightful discussion. W.A.G. received support from ONR (ONR N00014-18-1-2155). The Caltech High Performance Computing (HPC) center is acknowledged for support of computational resources. \n\nThe authors declare no competing financial interest.", revision_no = "20", abstract = "We utilize quantum mechanics to evaluate a variety of plausible mechanistic pathways for the entirety of the catalytic cycle for asymmetric decarboxylative allylic alkylation of allyl β-ketoesters. We present a mechanistic picture that unites all current experimental observations, including enantioinduction, reaction rate, catalyst resting state, enolate crossover experiments, water tolerance, and the effects of solvation on inner- and outer-sphere mechanisms. Experiments designed to evaluate the fidelity and predictive power of the computational models reveal the methods employed herein to be highly effective in elucidating the reactivity of the catalytic system. On the basis of these findings, we highlight a computational framework from which chemically accurate results are obtained and address the current limitations of the decarboxylative asymmetric allylic alkylation reaction.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/107230, title ="Synthesis of carboxylic acid and dimer ester surrogates to constrain the abundance and distribution of\nmolecular products in α-pinene and β-pinene secondary organic aerosol", author = "Kenseth, Christopher M. and Hafeman, Nicholas J.", pages = "ENVR-0004", month = "August", year = "2020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20201221-084129753", note = "© 2020 American Chemical Society.", revision_no = "12", abstract = "Liq. chromatog./neg. electrospray ionization mass spectrometry [LC/(-)ESI-MS] is routinely employed to characterize the\nidentity and abundance of mol. products in secondary org. aerosol (SOA) derived from monoterpene oxidn. Due to a\nlack of authentic stds., however, com. terpenoic acids (e.g., cis-pinonic acid) are typically used as surrogates to\nquantify both monomeric and dimeric SOA constituents. Here, we synthesize a series of enantiopure, pinene-derived\ncarboxylic acid and dimer ester homologues. We find that the (-)ESI efficiencies of the dimer esters are 19 to 36 times\nhigher than that of cis-pinonic acid, demonstrating that the mass contribution of dimers to monoterpene SOA has\nbeen significantly overestimated in past studies. Using the measured (-)ESI efficiencies of the carboxylic acids and\ndimer esters as more representative surrogates, we det. that mol. products measureable by LC/(-)ESI-MS account for\nonly 21.8 ± 2.6% and 18.9 ± 3.2% of the mass of SOA formed from ozonolysis of α-pinene and β-pinene, resp. The 28-\n36 identified monomers (C₇₋₁₀H₁₀₋₁₈O₃₋₆) constitute 15.6-20.5% of total SOA mass, whereas only 1.3-3.3% of the SOA\nmass is attributable to the 46-62 identified dimers (C₁₅₋₁₉H₂₄₋₃₂O₄₋₁₁). The distribution of identified α-pinene and β-pinene SOA mol. products is examd. as a function of carbon no. (n_C), av. carbon oxidn. state (OS_C), and volatility\n(C*). The obsd. order of magnitude difference in (-)ESI efficiency between monomers and dimers is expected to be\nbroadly applicable to other biogenic and anthropogenic SOA systems analyzed via (-) or (+) LC/ESI-MS, and\ndemonstrates that the use of unrepresentative surrogates can lead to substantial systematic errors in quant. LC/ESI-MS\nanalyses of SOA.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/104205, title ="Catalytic enantioselective synthesis of carbocyclic and heterocyclic spiranes via a decarboxylative aldol cyclization", author = "Inanaga, Kazato and Wollenburg, Marco", journal = "Chemical Science", volume = "11", number = "28", pages = "7390-7395", month = "July", year = "2020", doi = "10.1039/d0sc02366c", issn = "2041-6520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200702-103837298", note = "© 2020 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. \n\nAll publication charges for this article have been paid for by the Royal Society of Chemistry. \n\nReceived 26th April 2020; Accepted 20th June 2020; First published 23 Jun 2020. \n\nThis manuscript is dedicated to the memory of Prof. Teruaki Mukaiyama. The authors wish to thank NIH-NIGMS (R01GM080269), Astellas Pharma, Inc. (postdoctoral fellowship to K. I.), the Alfried Krupp von Bohlen and Halbach Foundation (fellowship to M. W.) and Amgen, Inc. (graduate fellowship to S. B.). We also thank Dr Scott C. Virgil for his support with chromatographic analysis, high-resolution mass analysis, and assistance during the crystallization process. \n\nThe authors declare no conflicts of interest.", revision_no = "20", abstract = "The synthesis of a variety of enantioenriched 1,3-diketospiranes from the corresponding racemic allyl β-ketoesters via an interrupted asymmetric allylic alkylation is disclosed. Substrates possessing pendant aldehydes undergo decarboxylative enolate formation in the presence of a chiral Pd catalyst and subsequently participate in an enantio- and diastereoselective, intramolecular aldol reaction to furnish spirocyclic β-hydroxy ketones which may be oxidized to the corresponding enantioenriched diketospiranes. Additionally, this chemistry has been extended to α-allylcarboxy lactam substrates leading to a formal synthesis of the natural product (−)-isonitramine.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/103952, title ="Probing Trends in Enantioinduction via Substrate Design: Palladium-Catalyzed Decarboxylative Allylic Alkylation of α-Enaminones", author = "Duquette, Douglas C. and Cusumano, Alexander Q.", journal = "Organic Letters", volume = "22", number = "13", pages = "4966-4969", month = "July", year = "2020", doi = "10.1021/acs.orglett.0c01441", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200622-104137176", note = "© 2020 American Chemical Society. \n\nReceived: April 25, 2020; Published: June 16, 2020. \n\nWe thank the NIH-NIGMS (R01GM080269), and the NSF (predoctoral research fellowship to D.C.D., No. DGE-1144469) for financial support. Research reported in this publication was supported by the NIH-NIGMS under Award Number F32GM116304 (postdoctoral fellowship to J. T. Moore). We further thank Dr. Scott C. Virgil (Caltech) for assistance with chiral-SFC separation and insightful discussion. \n\nThe authors declare no competing financial interest.", revision_no = "22", abstract = "Herein, we report the palladium-catalyzed decarboxylative asymmetric allylic alkylation of α-enaminones. In addition to serving as valuable synthetic building blocks, we exploit the α-enaminone scaffold and its derivatives as probes to highlight structural and electronic factors that govern enantioselectivity in this asymmetric alkylation reaction. Utilizing the (S)-t-BuPHOX ligand in a variety of nonpolar solvents, the alkylated products are obtained in up to 99% yield and 99% enantiomeric excess.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/103305, title ="Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Acyclic α-N-Pyrrolyl/Indolyl Ketones", author = "Lavernhe, Rémi and Alexy, Eric J.", journal = "Organic Letters", volume = "22", number = "11", pages = "4272-4275", month = "June", year = "2020", doi = "10.1021/acs.orglett.0c01303", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200519-093555551", note = "© 2020 American Chemical Society. \n\nReceived: April 14, 2020; Published: May 18, 2020. \n\nWe thank the NIH-NIGMS (R01GM080269), the Gordon and Betty Moore Foundation, and Caltech for financial support. E.J.A. thanks the National Science Foundation for a predoctoral fellowship. We thank Dr. David VanderVelde (Caltech) for NMR expertise. Dr. Scott Virgil (Caltech Center for Catalysis and Chemical Synthesis) is thanked for instrumentation and SFC assistance. Dr. Michael Takase (Caltech) and Lawrence Henling (Caltech) are acknowledged for X-ray analysis. \n\nThe authors declare no competing financial interest.", revision_no = "20", abstract = "The synthesis of fully substituted α-N-pyrrolyl and indolyl ketones via enantioselective palladium-catalyzed allylic alkylation is described. The acyclic ketones are alkylated in high yields with high enantioselectivities through the use of an electron-deficient phosphinooxazoline ligand, furnishing a highly congested and synthetically challenging stereocenter. The obtained alkylation products contain multiple reactive sites poised for additional functionalizations and diversification.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/102658, title ="Catalytic enantioselective synthesis of tetrasubstituted chromanones via palladium-catalyzed asymmetric conjugate arylation using chiral pyridine-dihydroisoquinoline ligands", author = "Baek, Doohyun and Ryu, Huijeong", journal = "Chemical Science", volume = "11", number = "18", pages = "4602-4607", month = "May", year = "2020", doi = "10.1039/d0sc00412j", issn = "2041-6520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200420-124420412", note = "© 2020 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. \n\nSubmitted 22 Jan 2020; Accepted 07 Apr 2020; First published 07 Apr 2020. \n\nThis research was supported by the “GIST-Caltech Research Collaboration” grant funded by the GIST in 2017. This research was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT) (NRF-2020R1A2C1009123). The NIH-NIGMS (R01GM080269) and Caltech are also thanked for support of our research program. \n\nThere are no conflicts to declare.", revision_no = "20", abstract = "Highly enantioselective conjugate addition reactions of arylboronic acids to 2-substituted chromones catalyzed by palladium complexes with new chiral Pyridine-Dihydroisoquinoline (PyDHIQ) ligands have been developed. These reactions provide highly enantioselective access to chromanones containing tetrasubstituted stereocenters. Various arylboronic acids and 2-substituted chromones can be used in the catalytic reaction to afford the chiral tetrasubstituted chromanones in good yields and excellent enantioselectivities (25 examples, up to 98% yields, up to 99% ee).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/101705, title ="The Total Synthesis of (–)-Scabrolide A", author = "Hafeman, Nicholas J. and Loskot, Steven A.", journal = "Journal of the American Chemical Society", volume = "142", number = "19", pages = "8585-8590", month = "May", year = "2020", doi = "10.1021/jacs.0c02513", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200304-101308383", note = "© 2020 American Chemical Society. \n\nReceived: March 3, 2020; Published: March 30, 2020. \n\nThe authors wish to thank NSF (CHE-1800511) as well as Caltech for funding this research. B.P.P. additionally thanks NSF for support in the form of a predoctoral fellowship. The authors thank Dr. David VanderVelde for NMR assistance and maintenance of the Caltech NMR facility as well as Max Kaiser for assistance with NMR interpretation, Dr. Michael Takase and Lawrence Henling for XRD assistance, and Dr. Mona Shahgholi and Naseem Torian for mass spectrometry assistance. Additionally, the authors would like to thank Prof. Jyh-Horng Sheu for kindly providing ¹H and ¹³C NMR spectra of isolated scabrolide A. \n\nAuthor Contributions: N.J.H. and S.A.L. contributed equally. \n\nThe authors declare no competing financial interest.", revision_no = "40", abstract = "The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular Diels–Alder reaction and an enone–olefin cycloaddition/fragmentation sequence are then employed to construct the fused [5–6–7] linear carbocyclic core of the molecule and complete the total synthesis.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/101219, title ="Iridium-Catalyzed Enantioselective and Diastereoselective Hydrogenation of 1,3-Disubstituted Isoquinolines", author = "Kim, Alexia N. and Ngamnithiporn, Aurapat", journal = "ACS Catalysis", volume = "10", number = "5", pages = "3241-3248", month = "March", year = "2020", doi = "10.1021/acscatal.0c00211", issn = "2155-5435", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200211-083029861", note = "© 2020 American Chemical Society. \n\nReceived: January 13, 2020; Revised: February 6, 2020; Published: February 10, 2020. \n\nWe thank the NIH-NIGMS (R01GM127972A) and Caltech for the support of our research program. A.N. thanks the Royal Thai Government Scholarship Program. E.R.W. was supported by a Postdoctoral Fellowship (PF-16-011-01-CDD) from the American Cancer Society. C.U.G. was supported by a Feodor Lynen Research Fellowship from the Alexander von Humboldt Foundation. We thank Dr. David VanderVelde (Caltech) and Maximilian B. Kaiser for NMR expertise and Dr. Michael Takase (Caltech) for assistance with X-ray analysis. \n\nAuthor Contributions: A.N.K. and A.N. contributed equally to this work and are listed alphabetically. \n\nThe authors declare no competing financial interest.", revision_no = "25", abstract = "The development of a general method utilizing a hydroxymethyl directing group for asymmetric hydrogenation of 1,3-disubstituted isoquinolines to provide chiral 1,2,3,4-tetrahydroisoquinolines is reported. The reaction, which utilizes [Ir(cod)Cl]₂ and a commercially available chiral xyliphos ligand, proceeds in good yield with high levels of enantioselectivity and diastereoselectivity (up to 95% ee and >20:1 dr) on a range of differentially substituted isoquinolines. Directing-group studies demonstrate that the hydroxymethyl functional group at the C1 position is more efficient at enabling hydrogenation in comparison to other substituents, although high levels of enantioselectivity were conserved across a variety of polar and nonpolar functional groups. By utilization of the generated chiral β-amino alcohol as a functional handle, the synthetic utility is further highlighted via the synthesis of 1,2-fused oxazolidine, oxazolidinone, and morpholinone tetrahydroisoquinolines in one step. Additionally, a non-natural analogue of the tetrahydroprotoberberine alkaloids was successfully synthesized.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/99942, title ="Copper-Catalyzed Enantioselective Allylic Alkylation with a γ-Butyrolactone-Derived Silyl Ketene Acetal", author = "Jette, Carina I. and Tong, Z. Jaron", journal = "Angewandte Chemie International Edition", volume = "59", number = "5", pages = "2033-2038", month = "January", year = "2020", doi = "10.1002/anie.201912618", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20191120-075819004", note = "© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nIssue Online: 24 January 2020; Version of Record online: 16 December 2019; Accepted manuscript online: 19 November 2019; Manuscript revised: 12 November 2019; Manuscript received: 06 October 2019. \n\nThe NIH‐NIGMS (R01GM080269) and Caltech are thanked for support of our research program. Financial support from Caltech and the Dow Next Generation Educator Fund is gratefully acknowledged (R.G.H.). C.I.J. thanks the National Science Foundation for a predoctoral fellowship. Alexander\u2005Q. Cusumano is thanked for assistance and helpful discussions, Dr. Scott Virgil for instrumentation and SFC assistance, Lawrence Henling for assistance with X‐Ray analysis, Dr. Mona Shahgholi for mass spectrometry assistance, Dr. Paul\u2005H. Oyala for his assistance with EPR spectroscopy, and Prof. H.\u2005B. Gray for the use of the Cary 500 UV‐vis‐NIR spectrophotometer. \n\nThe authors declare no conflict of interest.", revision_no = "30", abstract = "Herein, we report a Cu‐catalyzed enantioselective allylic alkylation using a γ‐butyrolactone‐derived silyl ketene acetal. Critical to the development of this work was the identification of a novel mono‐picolinamide ligand with the appropriate steric and electronic properties to afford the desired products in high yield (up to 96\u2009%) and high ee (up to 95\u2009%). Aryl, aliphatic, and unsubstituted allylic chlorides bearing a broad range of functionality are well‐tolerated. Spectroscopic studies reveal that a Cu^I species is likely the active catalyst, and DFT calculations suggest ligand sterics play an important role in determining Cu coordination and thus catalyst geometry.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/99689, title ="Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Protected Benzoin-Derived Enol Carbonates", author = "Lavernhe, Rémi and Alexy, Eric J.", journal = "Advanced Synthesis and Catalysis", volume = "362", number = "2", pages = "344-347", month = "January", year = "2020", doi = "10.1002/adsc.201901281", issn = "1615-4150", url = "https://resolver.caltech.edu/CaltechAUTHORS:20191106-101057290", note = "© 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nIssue Online: 23 January 2020; Version of Record online: 26 November 2019; Accepted manuscript online: 05 November 2019; Manuscript revised: 02 November 2019; Manuscript received: 03 October 2019. \n\nWe thank NIH-NIGMS (R01GM080269) and Caltech for financial support. E.J.A. thanks the National Science Foundation for a predoctoral fellowship. Larry Henling and Dr. Michael Takase are thanked for X-ray crystallographic structure determination. We thank Dr. David VanderVelde for NMR expertise and Dr. Scott Virgil for instrumentation and SFC assistance.", revision_no = "27", abstract = "The enantioselective palladium-catalyzed decarboxylative allylic alkylation of fully substituted α-hydroxy acyclic enol carbonates providing tetrasubstituted benzoin derivatives is reported. Investigation into the transformation revealed that preparation of the starting material as a single enolate isomer is crucial for optimal\nenantioselectivity. The obtained alkylation products\ncontain multiple reactive sites that can be utilized toward\nthe synthesis of stereochemically rich derivatives.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/99801, title ="Enantioselective Alkynylation of Trifluoromethyl Ketones Catalyzed by Cation-Binding Salen Nickel Complexes", author = "Park, Dongseong and Jette, Carina I.", journal = "Angewandte Chemie International Edition", volume = "59", number = "2", pages = "775-779", month = "January", year = "2020", doi = "10.1002/anie.201913057", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20191112-095230680", note = "© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nAccepted manuscript online: 12 November 2019; Manuscript accepted: 11 November 2019; Manuscript revised: 06 November 2019; Manuscript received: 12 October 2019. \n\nThis work was supported by the “GIST‐Caltech Research Collaboration” grant funded by the GIST in 2017, and by the National Research Foundation of Korea grant funded by the Korean Government (NRF‐2012R1A1A2044550, NRF‐2017M1A2A2049102). The NIH‐NIGMS (R01GM080269) and Caltech are also thanked for support of our research program. C.I.J. thanks the National Science Foundation for a predoctoral fellowship. \n\nThe authors declare no conflict of interest.", revision_no = "26", abstract = "Cation‐binding salen nickel catalysts were developed for the enantioselective alkynylation of trifluoromethyl ketones in high yield (up to 99\u2009%) and high enantioselectivity (up to 97\u2009% ee). The reaction proceeds with substoichiometric quantities of base (10–20 mol\u2009% KOt‐Bu) and open to air. In the case of trifluoromethyl vinyl ketones, excellent chemo‐selectivity was observed, generating 1,2‐addition products exclusively over 1,4‐addition products. UV‐vis analysis revealed the pendant oligo‐ether group of the catalyst strongly binds to the potassium cation (K⁺) with 1:1 binding stoichiometry (K_a=6.6×10⁵\u2009M⁻¹).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/100228, title ="Enantioselective Synthesis of 15-Deoxy-Δ¹²,¹⁴-Prostaglandin J₂", author = "Li, Jiaming and Stoltz, Brian M.", journal = "Organic Letters", volume = "21", number = "24", pages = "10139-10142", month = "December", year = "2019", doi = "10.1021/acs.orglett.9b04198", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20191209-080257479", note = "© 2019 American Chemical Society. \n\nReceived: November 22, 2019; Published: December 6, 2019. \n\nThe authors acknowledge the funding from NIH (R01GM031332 and R01GM080269). Materia, Inc. is thanked for generous donations of catalysts. Dr. Scott C. Virgil (Caltech) is thanked for assistance with chiral-SFC and HPLC separation. Dr. Zepeng Yang (Caltech) is thanked for assistance with HPLC data collection. Dr. William Wolf, Carina Jette, and Zach Sercel (Caltech) are thanked for helpful discussion and input on this manuscript. Dr. David VanderVelde (Caltech) and Dr. Mona Shahgholi (Caltech) are acknowledged for assistance with characterization. \n\nThe authors declare no competing financial interest.", revision_no = "19", abstract = "An enantioselective synthesis of 15-deoxy-Δ¹²,¹⁴-prostaglandin J₂ is reported. The synthesis begins with the preparation of enantiopure 3-oxodicyclopentadiene by a lipase-mediated kinetic resolution. A three-component coupling followed by a retro-Diels–Alder reaction provides the C8 stereochemistry of the prostaglandin skeleton with high enantioselectivity. Stereoretentive olefin metathesis followed by a Pinnick oxidation affords 15-deoxy-Δ¹²,¹⁴-prostaglandin J₂ in high enantiopurity.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/99133, title ="Enantioselective construction of the tricyclic core of curcusones A–D via a cross-electrophile coupling approach", author = "Wright, Austin C. and Stoltz, Brian M.", journal = "Chemical Science", volume = "10", number = "45", pages = "10562-10565", month = "December", year = "2019", doi = "10.1039/c9sc04127c", issn = "2041-6520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20191008-075046379", note = "© 2019 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. \n\nReceived 16th August 2019, Accepted 30th September 2019, First published on 1st October 2019. \n\nCaltech and the NSF (1800511) are thanked for supplying funding. Dr Scott Virgil is gratefully acknowledged for purification and crystallization expertise. We thank Dr Michael Takase and Dr Lawrence Henling for collecting X-ray crystallographic data. Dr Steven Loskot and Nicholas Hafeman are acknowledged for helpful discussions. \n\nThere are no conflicts to declare.", revision_no = "21", abstract = "Herein we report our recent progress toward the enantioselective total synthesis of the diterpenoid natural products curcusones A–D by means of complementary Stetter annulation or ring-closing metathesis (RCM) disconnections. Using the latter approach, we have achieved the concise construction of the 5–7–6 carbocyclic core embedded in each member of the curcusone family. Essential to this route is the use of a cross-electrophile coupling strategy, which has not previously been harnessed in the context of natural product synthesis.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/100047, title ="Progress toward the Enantioselective Synthesis of Curcusones A–D via a Divinylcyclopropane Rearrangement Strategy", author = "Wright, Austin C. and Lee, Chung Whan", journal = "Organic Letters", volume = "21", number = "23", pages = "9658-9662", month = "December", year = "2019", doi = "10.1021/acs.orglett.9b03829", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20191125-151328722", note = "© 2019 American Chemical Society. \n\nReceived: October 27, 2019. Publication Date:November 25, 2019. \n\nWe thank NSF (CHE-1800511), Amgen, and Caltech for funding this research. \n\nAuthor Contributions: A.C.W. and C.W.L. contributed equally. \n\nThe authors declare no competing financial interest.", revision_no = "23", abstract = "We report our iterative efforts toward the divergent total syntheses of curcusones A–D via Suzuki coupling, intramolecular cyclopropanation, and a key divinylcyclopropane rearrangement. Progress of our synthesis was repeatedly challenged by the highly substrate-dependent cyclopropanation step, which we could ultimately overcome by judicious choice of substituents on the six-membered ring fragment.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/99596, title ="Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of 1,4-Diazepan-5-ones", author = "Sercel, Zachary P. and Sun, Alexander W.", journal = "Organic Letters", volume = "21", number = "22", pages = "9158-9161", month = "November", year = "2019", doi = "10.1021/acs.orglett.9b03530", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20191031-141639871", note = "© 2019 American Chemical Society. \n\nReceived: October 6, 2019; Published: October 31, 2019. \n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for financial support. Z.P.S. thanks the Rose Hills Foundation for support via a Rose Hills Foundation Graduate Fellowship. A.W.S. thanks the NIH-NIGMS for a predoctoral fellowship (Ruth L. Kirschstein Institutional National Research Service Award F30GM120836) and a UCLA-Caltech Medical Scientist Training Program Fellowship (T32GM008042). Variable-temperature NMR spectra were obtained on a spectrometer funded by the NIH (RR027690). Dr. Scott Virgil (Caltech) and Dr. David VanderVelde (Caltech) are gratefully acknowledged for instrumentation and helpful discussions. Ky Nguyen (Caltech) is thanked for experimental assistance. \n\nAuthor Contributions: Z.P.S. and A.W.S. contributed equally. \n\nThe authors declare no competing financial interest.", revision_no = "31", abstract = "We report the palladium-catalyzed asymmetric allylic alkylation of 1,4-diazepan-5-ones. This reaction proceeds smoothly to give gem-disubstituted diazepanone heterocycles bearing various functional groups in up to >99% yield and up to 95% ee. An electron-rich p-anisoyl lactam protecting group and the use of a nonpolar solvent proved crucial to obtaining high enantioselectivity in most cases. Additionally, we demonstrate the use of our methodology in the synthesis of a gem-disubstituted analogue of the FDA-approved anti-insomnia drug suvorexant.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/99557, title ="Stereospecific Overman Rearrangement of Substituted Cyclic Vinyl Bromides: Access to Fully Substituted α-Amino Ketones", author = "Velasco-Rubio, Álvaro and Alexy, Eric J.", journal = "Organic Letters", volume = "21", number = "22", pages = "8962-8965", month = "November", year = "2019", doi = "10.1021/acs.orglett.9b03347", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20191030-100426727", note = "© 2019 American Chemical Society. \n\nReceived: September 21, 2019; Published: October 30, 2019. \n\nWe thank NIH-NIGMS (R01GM080269) and Caltech for financial support. A.V.-R. thanks Xunta de Galicia for a predoctoral fellowship (ED481A-2018/34, 2018-2021). E.J.A. thanks the National Science Foundation for a predoctoral fellowship. We thank Dr. David VanderVelde (Caltech) for NMR expertise. Larry Henling (Caltech) and Dr. Michael Takase (Caltech) are thanked for X-ray crystallographic structure determination. Dr. Scott Virgil (Caltech) is thanked for instrumentation and SFC assistance. \n\nAccession Codes: CCDC 1955048 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033. \n\nThe authors declare no competing financial interest. \n\nThis manuscript is dedicated to Professor Larry E. Overman (UC Irvine) for being an inspirational force in organic synthetic chemistry.", revision_no = "17", abstract = "A versatile thermal Overman rearrangement of enantioenriched, cyclic allylic alcohols providing tertiary allylic amines has been developed. The vinyl bromide used to control enantioselectivity in a preceding CBS reduction is utilized as a synthetic handle for the preparation of tertiary α-amino ketones and related derivatives in an asymmetric fashion.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/99769, title ="Transition‐Metal‐Free Catalytic C─H Bond Silylation", author = "Schuman, David P. and Liu, Wen‐Bo", pages = "213-240", month = "November", year = "2019", doi = "10.1002/9783527814787.ch7", isbn = "9783527344536", url = "https://resolver.caltech.edu/CaltechAUTHORS:20191111-083817296", note = "© 2020 Wiley‐VCH Verlag GmbH & Co. KGaA. \n\nPublished Online: 08 November 2019; Published Print: 11 November 2019.", revision_no = "7", abstract = "Herein, we provide a detailed look at the state of transition‐metal‐free catalytic C–H silylation with select examples to highlight specific advances during the field's recent development. The reactions are categorized by type of catalyst (i.e. Lewis acid, Brønsted acid, Brønsted base, and radical initiation catalysts). For each catalyst system presented, an overview of the substrate scope, mechanism (if known), and significant limitations is discussed.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/96670, title ="Modularity: Adding New Dimensions to Total Synthesis", author = "Sun, Alexander W. and Lackner, Sebastian", journal = "Trends in Chemistry", volume = "1", number = "7", pages = "630-643", month = "October", year = "2019", doi = "10.1016/j.trechm.2019.05.008", issn = "2589-5974", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190624-132958661", note = "© 2019 Elsevier Inc. \n\nAvailable online 21 June 2019. \n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for support of our research program. A.W.S. thanks the NIH-NIGMS for a predoctoral fellowship (Ruth L. Kirschstein Institutional National Research Service Award F30GM120836) and a UCLA-Caltech Medical Scientist Training Program Fellowship (T32GM008042). S.L. acknowledges the Deutsche Forschungsgemeinschaft (DFG) for a postdoctoral fellowship (LA 4220/1-1).", revision_no = "14", abstract = "As the field of synthetic chemistry seeks to tackle new frontiers, total synthesis is primed to address significant medical challenges such as the rise of antibiotic resistance and cancer. One emerging frontier focuses on increasingly concerted efforts to utilize modular total synthesis as a strategy to generate analogs of natural product targets for biological studies, with the ultimate goal of new therapeutic development. This new frontier is enabled by a confluence of human ingenuity in synthetic design, newly developed reactions that facilitate advances in total synthesis strategies, and emerging technologies. In this review, we highlight the evolving trend of modular total synthesis, including new reactions and automated technologies. This trend should lead to an increasingly important source of new medicines to improve human health.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/98492, title ="Characterization of Reactive Organometallic Species via MicroED", author = "Jones, Christopher G. and Asay, Matthew", journal = "ACS Central Science", volume = "5", number = "9", pages = "1507-1513", month = "September", year = "2019", doi = "10.1021/acscentsci.9b00403", issn = "2374-7943", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190906-134149357", note = "© 2019 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: April 19, 2019; Published: September 6, 2019. \n\nThe authors thank Michael R. Sawaya, Michael K. Takase, Michael J. Collazo, Marcus Gallagher-Jones, and Chih-Te Zee (University of California, Los Angeles) for technical expertise and inspirational discussions. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship (to C.G.J. and A.S.) under Grant No. DGE-1650604. This work is funded by STROBE, an NSF STC under Grant No. DMR 1548924. This work was supported by the University of California, Riverside. The solid-state NMR measurements at 14.1 T were recorded on an instrument supported by the National Science Foundation (CHE-1626673). V.L. acknowledges support from the National Science Foundation (CHE-1455348). J.A.R. acknowledges support from the Arnold and Mabel Beckman Foundation, the Pew Charitable Trusts, the Searle Scholars Program, the U.S. Department of Energy (Grant No. DE-FC02-02ER63421), and the National Institutes of Health—National Institute of General Medical Sciences (Grant Nos. P41 GM102403 and R35 GM128867). H.M.N. acknowledges support from the David and Lucile Packard Foundation, the Alfred P. Sloan Foundation, and the Pew Charitable Trusts. The authors thank the Beckman Institute Resource Center for Transmission Electron Microscopy at Caltech. \n\nAuthor Contributions: C.G.J. and M.A. contributed equally. C.G.J. performed experiments, developed the sample preparation techniques, processed and refined structural data, prepared figures, and assisted with manuscript preparation. M.A. prepared samples, refined structural data, and assisted with manuscript and figure preparation. L.J.K. performed experiments, processed structural data, prepared figures, and assisted with manuscript preparation. J.F.K. prepared isolated and characterized compounds. A.S. processed and refined data, wrote and executed MATLAB code, prepared figures, and assisted in manuscript preparation. T.J.F. performed experiments and assisted with manuscript preparation. K.R.B. prepared isolated and characterized compounds. D.C. assisted in processing and refining structural data and provided crystallographic expertise. A.G.M. assisted in data collection. M.P.C. performed solid-state NMR experiments. B.M.S. designed experiments and assisted with manuscript preparation. V.L. designed experiments and assisted with manuscript preparation. J.A.R. performed experiments, developed sample preparation techniques, maintained the microscope, analyzed data, and assisted with manuscript preparation. H.M.N. conceived of the project, designed experiments, performed experiments, developed the sample preparation techniques, and assisted with manuscript and figure preparation. \n\nThe authors declare no competing financial interest.", revision_no = "97", abstract = "Here we apply microcrystal electron diffraction (MicroED) to the structural determination of transition-metal complexes. We find that the simultaneous use of 300 keV electrons, very low electron doses, and an ultrasensitive camera allows for the collection of data without cryogenic cooling of the stage. This technique reveals the first crystal structures of the classic zirconocene hydride, colloquially known as “Schwartz’s reagent”, a novel Pd(II) complex not amenable to solution-state NMR or X-ray crystallography, and five other paramagnetic and diamagnetic transition-metal complexes.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/97229, title ="Incorporation of a chiral gem-disubstituted nitrogen heterocycle yields an oxazolidinone antibiotic with reduced mitochondrial toxicity", author = "Sun, Alexander W. and Bulterys, Philip L.", journal = "Bioorganic and Medicinal Chemistry Letters", volume = "29", number = "18", pages = "2686-2689", month = "September", year = "2019", doi = "10.1016/j.bmcl.2019.07.024", issn = "0960-894X", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190718-083115245", note = "© 2019 Elsevier Ltd. \n\nReceived 7 April 2019, Revised 8 July 2019, Accepted 13 July 2019, Available online 16 July 2019. \n\nA.W.S. and B.M.S conceived of the project. A.W.S., B.M.O, M.D.B., and S.C.V. performed experimental chemistry. P.L.B., P.A.J., and WuXi AppTec performed biological assays. M.D.B. performed VCD experiments. A.W.S., P.L.B., M.D.B., P.A.J., B.M.O., J.F.M., and B.M.S. wrote the manuscript. \n\nThe NIH-NIGMS (R01GM080269), Caltech, the Paul and Daisy Soros Foundation, the Cystic Fibrosis Foundation, and the UCLA-Caltech Medical Scientist Training Program are thanked for support of our research program. (Grants R01GM080269 to B.M.S., F30GM120836 and T32GM008042 to A.W.S., F30AI118342, T32GM008042 and P.D. Soros Fellowship to P.L.B., and a Cystic Fibrosis Foundation Fellowship to P.A.J.). Dr. David VanderVelde is thanked for assistance with structural assignments via NMR analysis. Dr. Justin Hilf is thanked for helpful discussions. Professor Dianne K. Newman is thanked for MIC testing. The CO-ADD is thanked for MIC testing. The UCLA Microbiology Laboratory is thanked for providing bacterial strains.", revision_no = "28", abstract = "gem-Disubstituted N-heterocycles are rarely found in drugs, despite their potential to improve the drug-like properties of small molecule pharmaceuticals. Linezolid, a morpholine heterocycle-containing oxazolidinone antibiotic, exhibits significant side effects associated with human mitochondrial protein synthesis inhibition. We synthesized a gem-disubstituted linezolid analogue that when compared to linezolid, maintains comparable (albeit slightly diminished) activity against bacteria, comparable in vitro physicochemical properties, and a decrease in undesired mitochondrial protein synthesis (MPS) inhibition. This research contributes to the structure-activity-relationship data surrounding oxazolidinone MPS inhibition, and may inspire investigations into the utility of gem-disubstituted N-heterocycles in medicinal chemistry.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/97769, title ="A Small-scale Procedure for Acid-catalyzed Ketal Formation", author = "Wright, Austin C. and Du, Yun Emily", journal = "Journal of Organic Chemistry", volume = "84", number = "17", pages = "11258-11260", month = "September", year = "2019", doi = "10.1021/acs.joc.9b01541", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190812-105551569", note = "© 2019 American Chemical Society. \n\nReceived: June 10, 2019; Published: August 12, 2019. \n\nCaltech and the NSF (1800511) are thanked for funding. We are grateful to Dr. Alexander Sun (Caltech) for photographic assistance. \n\nThe authors declare no competing financial interest.", revision_no = "18", abstract = "A modified procedure for dehydrative ketal protections is disclosed, which serves as an alternative to the classic Dean–Stark protocol. Studies show that this new procedure can outperform the Dean–Stark apparatus on small scales and thus serves as a complementary approach to effect dehydrative ketalizations. A detailed procedure for this apparatus is presented.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/96027, title ="Palladium-catalyzed α,β-dehydrogenation of acyclic ester equivalents promoted by a novel electron deficient phosphinooxazoline ligand", author = "Fulton, Tyler J. and Wu, Brenda", journal = "Tetrahedron", volume = "75", number = "31", pages = "4104-4109", month = "August", year = "2019", doi = "10.1016/j.tet.2019.05.065", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190603-092206331", note = "© 2019 Published by Elsevier Ltd. \n\nReceived 15 April 2019, Revised 24 May 2019, Accepted 29 May 2019, Available online 1 June 2019. \n\nDedicated to Professor John F. Hartwig on his receipt of the Tetrahedron Prize. \n\nWe thank NIH-NIGMS (R01GM080269), the Gordon and Betty Moore Foundation, and Caltech for financial support. E.J.A. thanks the National Science Foundation for a predoctoral fellowship. We thank Dr. David VanderVelde (Caltech) for NMR expertise. Dr. Scott Virgil (Caltech) is thanked for instrumentation and assistance.", revision_no = "19", abstract = "A unique example of Pd-catalyzed decarboxylative dehydrogenation of fully substituted N-acyl allyl enol carbonates is enabled by a new electron deficient phosphinooxazoline (PHOX) ligand. The reaction proceeds from the Z-enol carbonate to provide dehydrogenation products exclusively in high E/Z selectivity, while the E-enol carbonate provides the α-allylation product with only minor dehydrogenation. The reaction proceeds with a broad scope of Z-enol carbonates derived from N-acyl indoles to furnish acyclic formal α,β-unsaturated ester equivalents.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/95564, title ="Palladium-catalyzed enantioselective decarboxylative allylic alkylation of fully substituted N-acyl indole-derived enol carbonates", author = "Alexy, Eric J. and Fulton, Tyler J.", journal = "Chemical Science", volume = "10", number = "23", pages = "5996-6000", month = "June", year = "2019", doi = "10.1039/c9sc01726g", issn = "2041-6520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190517-104313815", note = "© 2019 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. \n\nReceived 8th April 2019, Accepted 26th April 2019, First published on 17th May 2019. \n\nWe thank NIH-NIGMS (R01GM080269), the Gordon and Betty Moore Foundation, and Caltech for financial support. E. J. A. thanks the National Science Foundation for a predoctoral fellowship. We thank Dr David VanderVelde (Caltech) for NMR expertise. Dr Scott Virgil (Caltech) is thanked for instrumentation and SFC assistance. Dr Michael Takase and Lawrene Henling are acknowledged for assistance with X-ray analysis. \n\nThere are no conflicts to declare.", revision_no = "23", abstract = "The first enantioselective palladium-catalyzed decarboxylative allylic alkylation of fully substituted N-acyl indole-derived enol carbonates forming acyclic all-carbon quaternary stereocenters is reported. Excellent yields up to 99% and enantioselectivities up to 98% ee are obtained through the use of a new electron-deficient phosphinoxazoline (PHOX) ligand. Control of substrate enolate geometry is crucial for high selectivity. The obtained α-quaternary N-acyl indoles are formal ester equivalents, and represent a useful handle for further synthetic transformations.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/95339, title ="Unified Enantioselective, Convergent Synthetic Approach Toward the Furanobutenolide-Derived Polycyclic Norcembranoid Diterpenes: Synthesis of a Series of Ineleganoloids by Oxidation State Manipulation of the Carbocyclic Core", author = "Craig, Robert A., II and Smith, Russell C.", journal = "Journal of Organic Chemistry", volume = "84", number = "12", pages = "7722-7746", month = "June", year = "2019", doi = "10.1021/acs.joc.9b00635", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190508-090511086", note = "© 2019 American Chemical Society. \n\nReceived: March 4, 2019; Published: May 8, 2019. \n\nThe authors wish to thank the NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support and Eli Lilly & Co. for assistance with biological activity screening. Additionally, the authors gratefully acknowledge Larry Henling and Dr. Michael Takase (Caltech) for X-ray crystallographic structural determination, Dr. Mona Shahgholi and Naseem Torian (Caltech) for mass spectrometry assistance, and Dr. David VanderVelde (Caltech) for NMR experimental assistance and helpful discussion. Additionally, Dr. Jeffrey C. Holder, Dr. Corey M. Reeves, Prof. Hosea M. Nelson, Dr. Jonny R. Gordon, Dr. Pamela M. Tadross, and Beau P. Pritchett (Caltech) are thanked helpful discussion. R.A.C. gratefully acknowledges the support of this work provided by a fellowship from the National Cancer Institute of the National Institutes of Health (NIH) under Award Number F31A17435. J.L.R. thanks the California Tobacco-Related Disease Research Program of the University of California, Grant Number 14DT-0004 for a predoctoral fellowship. A.C.J. thanks the NIH for the support of this work provided by a postdoctoral fellowship (award number F32GM082000). \n\nThe authors declare no competing financial interest.", revision_no = "25", abstract = "Late-stage synthetic efforts to advance the enatio- and diastereoselectively constructed [6,7,5,5]-fused tetracyclic scaffold toward the polycyclic norditerpenoid ineleganolide are disclosed. The described investigations focus on oxidation-state manipulation around the central cycloheptane ring. Computational evaluation of ground-state energies of dihydroineleganolide is used to rationalize empirical observations and provide insight for further synthetic development, enhancing the understanding of the conformational constraints of these compact polycyclic structures. Advanced synthetic manipulations generated a series of natural product-like compounds termed the ineleganoloids.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/93289, title ="Development of a catalytic enantioselective synthesis of the guanacastepene and heptemerone tricyclic core", author = "Harned, Andrew M. and Stoltz, Brian M.", journal = "Tetrahedron", volume = "75", number = "24", pages = "3166-3177", month = "June", year = "2019", doi = "10.1016/j.tet.2019.02.053", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190227-085618755", note = "© 2019 Published by Elsevier Ltd. \n\nReceived 12 January 2019, Revised 20 February 2019, Accepted 22 February 2019, Available online 27 February 2019. \n\nThis paper is dedicated to Professor Ryan A. Shenvi on receipt of the Tetrahedron Young Investigator Award. \n\nWe thank the NIH-NIGMS (R01GM080269 and postdoctoral fellowship F32GM073332 to A.M.H.), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support.", revision_no = "20", abstract = "For nearly two decades, synthetic chemists have been fascinated by the structural complexity and synthetic challenges afforded by the guanacastepene and heptemerone diterpenoids. Numerous synthetic approaches to these compounds have been reported, but to date the application of enantioselective catalysis to this problem has not been realized. Herein we report an enantioselective synthesis of an advanced intermediate corresponding to the tricyclic core common to the guanacastepenes and heptemerones. Highlights of this work include sequential Pd-catalyzed decarboxylative allylic alkylation reactions to generate the two all carbon quaternary stereocenters, the use of ring-closing metathesis to close the A ring in the presence of a distal allyl sidechain, and a regio- and diastereoselective oxidation of a trienol ether to introduce oxygenation on the A ring.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/94122, title ="An unexpected Ireland–Claisen rearrangement cascade during the synthesis of the tricyclic core of Curcusone C: Mechanistic elucidation by trial-and-error and automatic artificial force-induced reaction (AFIR) computations", author = "Lee, Chung Whan and Taylor, Buck L. H.", journal = "Journal of the American Chemical Society", volume = "141", number = "17", pages = "6995-7004", month = "May", year = "2019", doi = "10.1021/jacs.9b01146", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190325-131628168", note = "© 2019 American Chemical Society. \n\nReceived: January 30, 2019; Published: March 25, 2019. \n\nB.M.S. and C.W.L. thank the NSF (CHE-1800511), Amgen, and Caltech for support of this research. K.N.H. thanks the NSF (CHE-1361104 and 1764238) for financial support of this research. B.L.H.T. gratefully acknowledges the National Institutes of Health for a postdoctoral fellowship (F32GM106596). B.M.S. and K.N.H. thank the NSF under the CCI Center for Selective C−H Functionalization (CHE-1205646). Calculations were performed on the Hoffman2 Cluster at UCLA and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF (OCI-1053575). The authors thank Mr. Austin Wright (Caltech) for thoughtful comments about the manuscript. The co-authors dedicate this publication to the memory of Keiji Morokuma. \n\nAuthor Contributions: C.W.L. and B.L.H.T contributed equally. \n\nThe authors declare no competing financial interest.", revision_no = "25", abstract = "In the course of a total synthesis effort directed toward the natural product curcusone C, the Stoltz group discovered an unexpected thermal rearrangement of a divinylcyclopropane to the product of a formal Cope/1,3-sigmatropic shift sequence. Since the involvement of a thermally forbidden 1,3-shift seemed unlikely, theoretical studies involving two approaches, the “trial-and-error” testing of various conceivable mechanisms (Houk group) and an “automatic” approach using the Maeda–Morokuma AFIR method (Morokuma group) were applied to explore the mechanism. Eventually, both approaches converged on a cascade mechanism shown to have some partial literature precedent: Cope rearrangement/1,5-sigmatropic silyl shift/Claisen rearrangement/retro-Claisen rearrangement/1,5-sigmatropic silyl shift, comprising a quintet of five sequential thermally allowed pericyclic rearrangements.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/98403, title ="Discussion Addendum for: The Direct Acyl-Alkylation of Arynes. Preparation of Methyl 2-(2-acetylphenyl)acetate", author = "Wright, Austin C. and Stoltz, Brian M.", journal = "Organic Syntheses", volume = "96", pages = "80-97", month = "April", year = "2019", issn = "2333-3553", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190903-160057854", note = "© 2019 Organic Syntheses, Inc.", revision_no = "12", abstract = "For the past 50 years, benzynes and related arynes have been a major subject of study among physical organic chemists due to their unusual electronic and structural properties. However, the utility of these strained intermediates in the domain of chemical synthesis has only relatively recently undergone a vibrant expansion. The direct insertion of aryne and heteroaryne moieties into carbon-carbon and carbon-heteroatom σ bonds presents an intriguing and unique strategy for the rapid functionalization of aryl and heteroaryl systems. Following our 2009 Organic Syntheses article on the acyl-alkylation of arynes with β-ketoesters, there have been numerous reports of related transformations involving these highly reactive intermediates. This discussion addendum is intended to document advances made in the field of (hetero)arynes since our initial disclosure. Topics covered will be divided as follows: recent methods for the acyl-functionalization of arynes, syntheses of related strained systems, applications in heterocycle synthesis, miscellaneous transformations, and strategic uses in natural product synthesis. A supplemental review on aryne insertions into σ bonds is available. Applications of arynes in transition metal catalysis will not be discussed in detail, however there are thorough reviews on the subject.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/93305, title ="Cycloadditions of Oxacyclic Allenes and a Catalytic Asymmetric Entryway to Enantioenriched Cyclic Allenes", author = "Yamano, Michael M. and Knapp, Rachel R.", journal = "Angewandte Chemie International Edition", volume = "58", number = "17", pages = "5653-5657", month = "April", year = "2019", doi = "10.1002/anie.201900503", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190227-131909461", note = "© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nAccepted manuscript online: 27 February 2019; Manuscript accepted: 25 February 2019; Manuscript revised: 24 February 2019; Manuscript received: 21 January 2019. \n\nThe authors are grateful to NIH‐NIGMS (R01 GM123299‐01A1 and R01 GM117016 to N.K.G. and R01GM080269 to B.M.S), Caltech, the Trueblood Family (to N.K.G.) and UCLA for support. M.M.Y. acknowledges the National Science Foundation GRFP (DGE‐1144087) and the Foote Family. A.N. thanks the Royal Thai Government Scholarship Program. Dr. Scott Virgil (Caltech) is thanked for instrumentation and SFC assistance. These studies were supported by shared instrumentation grants from the NSF (CHE‐1048804) and the National Center for Research Resources (S10RR025631). This study used computational and storage services associated with the Hoffman2 Shared Cluster provided by UCLA Institute for Digital Research and Education's Research Technology Group. \n\nThe authors declare no conflict of interest.", revision_no = "21", abstract = "The chemistry of strained cyclic alkynes has undergone a renaissance over the past two decades. However, a related species, strained cyclic allenes, especially heterocyclic derivatives, have only recently resurfaced and represent another class of valuable intermediates. We report a mild and facile means to generate the parent 3,4‐oxacyclic allene from a readily accessible silyl triflate precursor, and then trap it in (4+2), (3+2), and (2+2) reactions to provide a variety of cycloadducts. In addition, we describe a catalytic, decarboxylative asymmetric allylic alkylation performed on an α‐silylated substrate, to ultimately permit access to an enantioenriched allene. Generation and trapping of the enantioenriched cyclic allene occurs with complete transfer of stereochemical information in a Diels–Alder cycloaddition through a point‐chirality,\u2009axial‐chirality,\u2009point‐chirality transfer process.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/94469, title ="Discussion Addendum for: Preparation of (S)-tert-ButylPHOX and (S)-2-Allyl-2-Methylcyclohexanone", author = "Sun, Alexander W. and Stoltz, Brian M.", month = "April", year = "2019", doi = "10.1002/0471264229.os095.29", isbn = "9780471264224", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190404-143251363", note = "© 2019 by Organic Syntheses, Inc. Published by John Wiley and Sons, Inc. \n\nPublished Online: 02 April 2019.", revision_no = "10", abstract = "[no abstract]", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/94105, title ="Enantioselective synthesis of gem-disubstituted N-Boc diazaheterocycles via decarboxylative asymmetric allylic alkylation", author = "Sun, Alexander and Stoltz, Brian Mark", pages = "ORGN-0601", month = "April", year = "2019", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190325-092717158", note = "© 2019 American Chemical Society.", revision_no = "11", abstract = "An enantioselective synthesis of diverse N4-Boc-protected a,a-disubstituted piperazin-2-ones using the\npalladiumcatalyzed decarboxylative allylic alkylation reaction has been achieved. Using a chiral Pd-catalyst derived from\nan electron deficient PHOX ligand, chiral piperazinones are synthesized in high yields and enantioselectivity. The chiral\npiperazinone products can be deprotected and reduced to valuable gem-disubstituted piperazines. This reaction is\nfurther extended to enable the enantioselective synthesis of a,a-disubstituted tetrahydropyrimidin-2-ones, which are\nhydrolyzed into corresponding chiral b2,2-amino acids.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/92451, title ="Palladium-Catalyzed Construction of Quaternary Stereocenters by Enantioselective Arylation of γ-Lactams with Aryl Chlorides and Bromides", author = "Jette, Carina I. and Geibel, Irina", journal = "Angewandte Chemie International Edition", volume = "58", number = "13", pages = "4297-4301", month = "March", year = "2019", doi = "10.1002/anie.201814475", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190124-110425627", note = "© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nAccepted manuscript online: 24 January 2019; Manuscript accepted: 21 January 2019; Manuscript revised: 20 January 2019; Manuscript received: 20 December 2018. \n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for\nsupport of our research program. C. I. Jette thanks the National Science Foundation for a predoctoral fellowship. I. Geibel acknowledges the Deutsche Forschungsgemeinschaft (DFG) for a postdoctoral fellowship (GE 3082/1-1). H.S. thanks Shionogi & Co., Ltd. for a research grant and fellowship. J. B. Morgan acknowledges the University of North Carolina Wilmington for research reassignment and travel funds. Dr. Scott Virgil (Caltech) is thanked\nfor instrumentation and SFC assistance.", revision_no = "21", abstract = "Herein, we report the first Pd‐catalyzed enantioselective arylation of α‐substituted γ‐lactams. Two sets of conditions were developed for this transformation, allowing for the use of either aryl chlorides or bromides as electrophiles. Utilizing a highly electron‐rich, dialkylphosphine ligand, we have been able to construct α‐quaternary centers in good yields (up to 91% yield) and high enantioselectivities (up to 97% ee).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/90863, title ="Atroposelective Synthesis of PINAP via Dynamic Kinetic Asymmetric Transformation", author = "Han, Seo-Jung and Bhat, Vikram", journal = "Advanced Synthesis and Catalysis", volume = "361", number = "3", pages = "441-444", month = "February", year = "2019", doi = "10.1002/adsc.201801248", issn = "1615-4150", url = "https://resolver.caltech.edu/CaltechAUTHORS:20181113-112609134", note = "© 2018 WILEY‐VCH Verlag. \n\nIssue Online: 01 February 2019; Version of Record online: 07 December 2018; Accepted manuscript online: 08 November 2018; Manuscript revised: 08 November 2018; Manuscript received: 18 September 2018. \n\nThe authors wish to thank NIH‐NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support. S.‐J.H. thanks the Fulbright program (Foreign Student Program, No. 15111120), the Ilju Foundation of Education & Culture (Pre‐doctoral Research Fellowship), and the KIST institutional program (2E28570, 2E28010) for financial support.", revision_no = "18", abstract = "The atroposelective synthesis of PINAP ligands has been accomplished via a palladium‐catalyzed C−P coupling process through dynamic kinetic asymmetric transformation. These catalytic conditions allow access to a wide variety of alkoxy‐ and benzyloxy‐substituted PINAP ligands in high enantiomeric excess. The methods described in this communication afford valuable P,N ligands in good yields and high enantioselectivity using low catalyst loading.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/90670, title ="Enantioselective synthesis of gem-disubstituted N-Boc diazaheterocycles via decarboxylative asymmetric allylic alkylation", author = "Sun, Alexander W. and Hess, Stephan N.", journal = "Chemical Science", volume = "10", number = "3", pages = "788-792", month = "January", year = "2019", doi = "10.1039/c8sc03967d", issn = "2041-6520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20181106-111914131", note = "© 2018 The Royal Society of Chemistry. Open Access Article. Published on 31 October 2018. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. \n\nAll publication charges for this article have been paid for by the Royal Society of Chemistry. \n\nThe article was received on 06 Sep 2018, accepted on 29 Oct 2018 and first published on 31 Oct 2018. \n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for support of our research program. Additionally, A. W. S. thanks the NIH-NIGMS for a predoctoral fellowship (Ruth L. Kirschstein Institutional National Research Service Award F30GM120836) and a UCLA-Caltech Medical Scientist Training Program Fellowship (T32GM008042). S. N. H. thanks the Bayer Foundation for an Otto Bayer Scholarship. Dr David VanderVelde is thanked for assistance with structural assignments via NMR analysis. Dr Scott Virgil, Dr Marchello Cavitt, Dr Brendan O'Boyle, Dr Justin Hilf, Dr Corey Reeves, and Kevin Yang are thanked for helpful discussions.", revision_no = "22", abstract = "An enantioselective synthesis of diverse N4-Boc-protected α,α-disubstituted piperazin-2-ones using the palladium-catalyzed decarboxylative allylic alkylation reaction has been achieved. Using a chiral Pd-catalyst derived from an electron deficient PHOX ligand, chiral piperazinones are synthesized in high yields and enantioselectivity. The chiral piperazinone products can be deprotected and reduced to valuable gem-disubstituted piperazines. This reaction is further extended to enable the enantioselective synthesis of α,α-disubstituted tetrahydropyrimidin-2-ones, which are hydrolyzed into corresponding chiral β^(2,2)-amino acids.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/91948, title ="Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis", author = "Welin, Eric R. and Ngamnithiporn, Aurapat", journal = "Science", volume = "363", number = "6424", pages = "270-275", month = "January", year = "2019", doi = "10.1126/science.aav3421", issn = "0036-8075", url = "https://resolver.caltech.edu/CaltechAUTHORS:20181221-091725806", note = "© 2018 American Association for the Advancement of Science. \n\n6 September 2018; accepted 26 November 2018; Published online 20 December 2018. \n\nThe authors thank Stig H. Christensen for experimental assistance and M. Takase and L. Henling for assistance with x-ray structure determination. \n\nResearch reported in this publication was supported by the NIH National Institute of General Medical Sciences (R01 127972), the Margaret E. Early Medical Research Trust, the NSF under the CCI Center for Selective C−H Functionalization (CHE-1205646), the Teva Pharmaceuticals Marc A. Goshko Memorial Grant Program, and the California Institute of Technology RI2 Program. E.R.W. was supported by a Postdoctoral Fellowship, PF-16-011-01-CDD, from the American Cancer Society. A.N. was supported by the Royal Thai Government Scholarship program. M.K. was supported by a postdoctoral fellowship from the German Academic Exchange Service. G.L. was supported by the Swiss National Science Foundation. G.M.P. was supported by an Erwin Schroedinger Fellowship, J 3893–N34, from the Austrian Science Fund (FWF). P.M.T. was supported by a graduate fellowship from the California HIV/AIDS Research Program. E.G. was supported by Knud Højgaards Fond and Oticon Fonden. C.U.G. was supported by a Feodor Lynen Research Fellowship from the Alexander von Humboldt Foundation. \n\nAuthor contributions: B.M.S. conceived and directed the project. E.R.W., C.D.G, P.M.T., K.M.A., and B.M.S. conceptualized and designed the synthetic strategy. E.R.W., A.N., M.K., G.L., G.M.P., C.D.G., P.M.T., C.K.H., K.N., E.G., and C.U.G. designed, performed, and analyzed the synthetic chemistry experiments. E.R.W., A.N., and G.M.P. designed and synthesized bis-THIQ analogs 31–34. D.J.S., M.S.J.M. and D.C. designed, performed, and analyzed biological activity experiments. S.C.V. assisted with experimental design and purification and obtained x-ray quality crystals of bis-THIQ 27. E.R.W., A.N., G.M.P., and B.M.S. prepared the manuscript. D.J.S. and B.M.S. acquired funding for the project. \n\nData and materials availability: Crystallographic parameters for compound 27 are available free of charge from the Cambridge Crystallographic Data Centre under CCDC 1875455. Data are available in the supplementary materials. The molecular characterization of the cell lines used in this Report has been deposited in the GEO public database (GEO:GSE18496). \n\nCompeting interests: B.M.S. has received financial support unrelated to the current science from 1200 Pharma, LLC, Novartis, Holoclara, and Amgen. B.M.S. is a co-founder of 1200 Pharma, LLC. D.J.S. has received financial support unrelated to the current science from Pfizer, Novartis, Eli Lilly and Company, and BioMarin Pharmaceutical. D.J.S. is a paid consultant to Novartis and Eli Lilly and Company. The California Institute of Technology holds a patent application on methods for preparing bis-tetrahydroisoquinoline-containing compounds (US patent application 16/038,968; international patent application PCT/US18/42710), on which E.R.W., A.N., M.K., G.L., G.M.P., C.D.G., P.M.T., C.K.H., K.N., C.U.G., K.M.A., S.C.V., and B.M.S. are named as inventors. ", revision_no = "72", abstract = "The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong gram-positive and -negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of non-natural analogs.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/91848, title ="Intramolecular Hydrogen Shift Chemistry of Hydroperoxy-Substituted Peroxy Radicals", author = "Praske, Eric and Otkjær, Rasmus V.", journal = "Journal of Physical Chemistry A", volume = "123", number = "2", pages = "590-600", month = "January", year = "2019", doi = "10.1021/acs.jpca.8b09745", issn = "1089-5639", url = "https://resolver.caltech.edu/CaltechAUTHORS:20181217-080428895", note = "© 2018 American Chemical Society. \n\nReceived: October 5, 2018; Revised: December 10, 2018;\nPublished: December 14, 2018.\n\nJ.C.H. thanks the Camille and Henry Dreyfus postdoctoral program in Environmental Chemistry for support. We acknowledge funding from the National Science Foundation (Grant CHE-1508526), the University of Copenhagen, and the Danish Center for Scientific Computing.\n\nThe authors declare no competing financial interest.\n\nThe wB97X-D/aug-cc-pVTZ optimizations and frequencies and the CCSD(T)-F12a/VDZ-F12 single point energy calculations are available at https://sid.erda.dk/public/archives/4f4b98346d6b007ba44411c642b39fa1/published-archive.html.", revision_no = "19", abstract = "Gas-phase autoxidation – the sequential regeneration of peroxy radicals (RO_2) via intramolecular hydrogen shifts (H-shifts) followed by oxygen addition – leads to the formation of organic hydroperoxides. The atmospheric fate of these peroxides remains unclear, including the potential for further H-shift chemistry. Here, we report H-shift rate coefficients for a system of RO_2 with hydroperoxide functionality produced in the OH-initiated oxidation of 2-hydroperoxy-2-methylpentane. The initial RO_2 formed in this chemistry are unable to undergo α-OOH H-shift (HOOC–H) reactions. However, these RO_2 rapidly isomerize (>100 s^(–1) at 296 K) by H-shift of the hydroperoxy hydrogen (ROO–H) to produce a hydroperoxy-substituted RO_2 with an accessible α-OOH hydrogen. First order rate coefficients for the 1,5 H-shift of the α-OOH hydrogen are measured to be ∼0.04 s^(–1) (296 K) and ∼0.1 s^(–1) (318 K), within 50% of the rate coefficients calculated using multiconformer transition state theory. Reaction of the RO_2 with NO produces alkoxy radicals which also undergo rapid isomerization via 1,6 and 1,5 H-shift of the hydroperoxy hydrogen (ROO–H) to produce RO_2 with alcohol functionality. One of these hydroxy-substituted RO_2 exhibits a 1,5 α-OH (HOC–H) H-shift, measured to be ∼0.2 s^(–1) (296 K) and ∼0.6 s^(–1) (318 K), again in agreement with the calculated rates. Thus, the rapid shift of hydroperoxy hydrogens in alkoxy and peroxy radicals enables intramolecular reactions that would otherwise be inaccessible.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/91707, title ="Concise Syntheses of Δ^(12)-Prostaglandin J Natural Products via Stereoretentive Metathesis", author = "Li, Jiaming and Ahmed, Tonia S.", journal = "Journal of the American Chemical Society", volume = "141", number = "1", pages = "154-158", month = "January", year = "2019", doi = "10.1021/jacs.8b12816", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20181212-100802379", note = "© 2018 American Chemical Society. \n\nReceived: November 29, 2018; Published: December 12, 2018. \n\nWe acknowledge funding from NIH (R01GM031332 and R01GM080269) and NSF CHE 150216. T.S.A. acknowledges NSF for support through a graduate research fellowship. Materia, Inc. is thanked for generous donations of catalysts. A. W. Sun, E. R. Welin, and Y. Xu are thanked for helpful discussion and input on this paper. Dr. Scott C. Virgil (Caltech) is thanked for assistance with chiral-SFC and HPLC separation. K. Chen from F. H. Arnold lab is thanked for his help with Biotage separation. Dr. David VanderVelde (Caltech) and Dr. Mona Shahgholi (Caltech) are acknowledged for help in structural determination and characterizations. This paper is dedicated to Professor E. J. Corey on the occasion of his 90th birthday. \n\nThe authors declare no competing financial interest.", revision_no = "20", abstract = "Δ^(12)-Prostaglandin J family is recently discovered and has potent anticancer activity. Concise syntheses of four Δ^(12)-prostaglandin J natural products (7–8 steps in the longest linear sequences) are reported, enabled by convergent stereoretentive cross-metathesis. Exceptional control of alkene geometry was achieved through stereoretention.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/91508, title ="Intermolecular Stereoselective Iridium-Catalyzed Allylic \nAlkylation: An Evolutionary Account", author = "Shockley, Samantha E. and Hethcox, J. Caleb", journal = "Synlett", volume = "29", number = "19", pages = "2481-2492", month = "December", year = "2018", doi = "10.1055/s-0037-1610217", issn = "0936-5214", url = "https://resolver.caltech.edu/CaltechAUTHORS:20181205-140604109", note = "© 2018 Georg Thieme Verlag Stuttgart. \n\nReceived: 28.05.2018; Accepted after revision: 25.06.2018; Published online: 15.08.2018. \n\nSupport for our program has been made available from the NIH-NIGMS (R01GM080269) and Caltech. Additionally, J.C.H. thanks the Camille and Henry Dreyfus postdoctoral program in Environmental Chemistry, and S.E.S. thanks the NIH-NIGMS for a predoctoral fellowship (F31GM120804). \n\nThe authors thank the many past and present co-workers whose efforts have made our contributions in iridium-catalyzed allylic alkylation possible: Prof. Wen-Bo Liu, Dr. Corey M. Reeves, Dr. Scott C. Virgil, Dr. Noriko Okamoto, Eric J. Alexy, Dr. Allen Y. Hong, and Dr. Kristy Tran.", revision_no = "16", abstract = "Our lab has long been interested in the development of methods for the creation of enantioenriched all-carbon quaternary stereocenters. Historically, our interest has centered on palladium-catalyzed allylic alkylation, though recent efforts have moved to include the study of iridium catalysts. Whereas palladium catalysts enable the preparation of isolated stereocenters, the use of iridium catalysts allows for the direct construction of vicinal stereocenters via an enantio-, diastereo-, and regioselective allylic alkylation. This Account details the evolution of our research program from inception, which focused on the first iridium-catalyzed allylic alkylation to prepare stereodyads containing a single quaternary stereocenter, to our most recent discovery that allows for the synthesis of vicinal quaternary centers.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/90583, title ="The CryoEM Method MicroED as a Powerful Tool for Small Molecule Structure Determination", author = "Jones, Christopher G. and Martynowycz, Michael W.", journal = "ACS Central Science", volume = "4", number = "11", pages = "1587-1592", month = "November", year = "2018", doi = "10.1021/acscentsci.8b00760", issn = "2374-7943", url = "https://resolver.caltech.edu/CaltechAUTHORS:20181101-140146236", note = "© 2018 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: October 17, 2018; Published: November 2, 2018. \n\nAccession Codes: Data and materials availability: MicroED density maps have been deposited to the PDB (thiostrepton, 6MXF), EMDB (EMD-9282, EMD-9284, EMD-9285, EMD-9286, EMD-9287, EMD-9288, EMD-9289, EMD-9290, EMD-9291, EMD-9292), and CCDC (1876036, 1876037, 1876038, 1876039, 1876040, 1876041, 1876042, 1876043, 1876044, 1876045). \n\nAuthor Contributions: C.G.J. and M.W.M. contributed equally. C.G.J. performed experiments, developed the sample preparation techniques, refined structural data, prepared figures, and assisted with manuscript preparation. M.W.M performed experiments, developed the sample preparation techniques, collected data, refined structural data, prepared figures, and assisted with manuscript preparation. T.F. performed experiments. J.H. wrote the software for image conversion, participated in data analysis, refinement, and structure determination. J.A.R. performed experiments, developed the sample preparation techniques, and assisted with manuscript preparation. B.M.S. conceived of the project, designed experiments, and assisted with manuscript preparation. H.M.N. conceived of the project, designed experiments, performed experiments, developed the sample preparation techniques, and assisted with manuscript and figure preparation. T.G. performed experiments, collected data, developed the sample prep techniques, developed microscope data collection parameters, provided the microscope and expertise, and assisted in manuscript and figure preparation. \n\nC.G.J. would like to acknowledge the National Science Foundation for a predoctoral fellowship (DGE-1650604). B.M.S. acknowledges the NIH-NIGMS for generous funding (R01GM080269). J.A.R. is supported by DOE Grant DE-FC02-02ER63421, NIH-NIGMS Grant R35GM128867, and as a Beckman Young Investigator, a Searle Scholar, and a Pew Scholar. H.M.N. thanks The Packard Foundation, The Sloan Foundation, Pew Charitable Trusts, and the NIH-NIGMS (R35 GM128936) for generous funding. The Gonen laboratory is supported by funds from the Howard Hughes Medical Institute. \n\nThe authors declare no competing financial interest. \n\nWe thank Profesor Doug Rees (Caltech), Professor Bil Clemons (Caltech), and Dr. Michael Sawaya (UCLA) for useful discussions. We thank Byungkuk Yoo and Michael Takase (Caltech) for technical assistance with data analysis. We thank Beau Pritchett and Hendrik Klare for providing synthetic samples.", revision_no = "41", abstract = "In the many scientific endeavors that are driven by organic chemistry, unambiguous identification of small molecules is of paramount importance. Over the past 50 years, NMR and other powerful spectroscopic techniques have been developed to address this challenge. While almost all of these techniques rely on inference of connectivity, the unambiguous determination of a small molecule’s structure requires X-ray and/or neutron diffraction studies. In practice, however, X-ray crystallography is rarely applied in routine organic chemistry due to intrinsic limitations of both the analytes and the technique. Here we report the use of the electron cryo-microscopy (cryoEM) method microcrystal electron diffraction (MicroED) to provide routine and unambiguous structural determination of small organic molecules. From simple powders, with minimal sample preparation, we could collect high-quality MicroED data from nanocrystals (∼100 nm, ∼10^(–15) g) resulting in atomic resolution (<1 Å) crystal structures in minutes.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/90452, title ="New directions in natural product synthesis", author = "Davies, Huw M. L. and Itami, Kenichiro", journal = "Chemical Society Reviews", volume = "47", number = "21", pages = "7828-7829", month = "November", year = "2018", doi = "10.1039/c8cs90115e", issn = "0306-0012", url = "https://resolver.caltech.edu/CaltechAUTHORS:20181029-094838158", note = "© The Royal Society of Chemistry 2018. \n\nReceived 11th October 2018. \n\nThis article is part of the themed collection: New Directions in Natural Product Synthesis.", revision_no = "9", abstract = "Research in the total synthesis of natural products has changed considerably in recent years. Much of the research effort has moved away from only focusing on the synthesis of a specific natural product, and instead toward the development of general synthetic strategies that enable the synthesis of a broad family of natural products. The new approach offers considerable advantages because the new synthetic strategies are often very flexible and thus, can have lasting influence on the field of organic synthesis. This thematic issue highlights several of the recently developed synthetic strategies and illustrates their flexibility for the synthesis of complex natural products. The thematic issue also includes reviews on visual algorithms to compare the efficiency of different total syntheses and computational approaches that can assist in the design of new total synthesis approaches.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/89676, title ="Catalyst-Controlled Selective Functionalization of Unactivated C–H Bonds in the Presence of Electronically Activated C–H Bonds", author = "Liu, Wenbin and Ren, Zhi", journal = "Journal of the American Chemical Society", volume = "140", number = "38", pages = "12247-12255", month = "September", year = "2018", doi = "10.1021/jacs.8b07534", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180917-125103681", note = "© 2018 American Chemical Society. \n\nReceived: July 24, 2018. Publication Date (Web): September 17, 2018. \n\nWe thank Dr. LaDena A. Bolton for preliminary studies on the thiophene derivatized substrates. Financial support was provided by NSF under the CCI Center for Selective C–H Functionalization (CHE-1700982). E.L.G. recognizes the NSF for a predoctoral research fellowship (No. DGE-1745301). D.G.M. acknowledges an NSF MRI-R2 Grant (CHE-0958205) and the use of the resources of the Cherry Emerson Center for Scientific Computation. Funds to purchase the NMR and X-ray spectrometers used in these studies were supported by the NSF (CHE 1531620 and CHE 1626172). \n\nThe authors declare the following competing financial interest(s): HMLD is a named inventor on a patent entitled, Dirhodium Catalyst Compositions and Synthetic Processes Related There-to (US 8,974,428, issued March 10, 2015). The other authors have no competing financial interests.", revision_no = "34", abstract = "A new chiral dirhodium tetracarboxylate catalyst, Rh_2(S-2-Cl-5-BrTPCP)_4, has been developed for C–H functionalization reactions by means of donor/acceptor carbene intermediates. The dirhodium catalyst contains four (S)-1-(2-chloro-5-bromophenyl)-2,2-diphenylcyclopropane-1-carboxylate ligands, in which all four 2-chloro-5-bromophenyl groups are on the same face of the catalyst, leading to a structure, which is close to C_4 symmetric. The catalyst induces highly site selective functionalization of remote, unactivated methylene C–H bonds even in the presence of electronically activated benzylic C–H bonds, which are typically favored using earlier established dirhodium catalysts, and the reactions proceed with high levels of diastereo- and enantioselectivity. This C–H functionalization method is applicable to a variety of aryl and heteroaryl derivatives. Furthermore, the potential of this methodology was illustrated by sequential C–H functionalization reactions to access the macrocyclic core of the cylindrocyclophane class of natural products.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/89379, title ="Palladium-Catalyzed Enantioselective C_(sp)^3–C_(sp)^3 Cross-Coupling for the Synthesis of (Poly)fluorinated Chiral Building Blocks", author = "Lu, Yanhui and Goldstein, Elizabeth L.", journal = "Organic Letters", volume = "20", number = "18", pages = "5657-5660", month = "September", year = "2018", doi = "10.1021/acs.orglett.8b02369", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180905-091810349", note = "© 2018 American Chemical Society. \n\nReceived: July 26, 2018; Published: September 5, 2018.\n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for support of our research program. E.L.G. recognizes the NSF for a predoctoral research fellowship (No. DGE-1745301). Y.L. thanks the Program of Leading Graduate Schools: IGER Program in Green Natural Sciences (MEXT) at Nagoya University for financial support. \n\nThe authors declare no competing financial interest.", revision_no = "23", abstract = "A general method for the enantioselective synthesis of carbo- and heterocyclic carbonyl compounds bearing fluorinated α-tetrasubstituted stereocenters using palladium-catalyzed decarboxylative allylic alkylation is described. The stereoselective C_(sp)^3–C_(sp)^3 cross-coupling reaction delivers five- and six-membered ketone and lactam products bearing (poly)fluorinated tetrasubstituted chiral centers in high yields and enantioselectivities. These fluorinated, stereochemically rich building blocks hold potential value in medicinal chemistry and are prepared using an orthogonal and enantioselective approach into such chiral moieties compared to traditional approaches, often without the use of electrophilic fluorinating reagents.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/88604, title ="General and Practical Potassium Methoxide/Disilane-Mediated Dehalogenative Deuteration of (Hetero)Arylhalides", author = "Wang, Xin and Zhu, Ming-Hui", journal = "Journal of the American Chemical Society", volume = "140", number = "35", pages = "10970-10974", month = "September", year = "2018", doi = "10.1021/jacs.8b07597", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180806-125449354", note = "© 2018 American Chemical Society. \n\nReceived: July 18, 2018; Published: August 3, 2018.\n\nWe gratefully acknowledge the NSFC (21602160, 21772148), the Fundamental Research Funds for the Central Universities (2042018kf0017), the NSF under the CCI Center for Selective C–H Functionalization (CCHF), CHE-1700982, National Program for 1000 Young Talents of China, Wuhan University, and Caltech for financial support. Prof. Qiang-Hui Zhou and his group are appreciated for generously sharing their lab space. Profs. Martin Oestreich (T.U. Berlin), Nasri Nesnas (F.I.T.), and Yong Liang (Nanjing Univ.) are thanked for helpful discussions. We also thank Dr. Hongbing Liu (Wuhan Institute of Physics and Mathematics, CAS) for the measurements of ^2H NMR spectra.\n\nThe authors declare no competing financial interest.\n\nA provisional patent has been filed.", revision_no = "23", abstract = "Herein we describe a general, mild and scalable method for deuterium incorporation by potassium methoxide/hexamethyldisilane-mediated dehalogenation of arylhalides. With CD3CN as a deuterium source, a wide array of heteroarenes prevalent in pharmaceuticals and bearing diverse functional groups are labeled with excellent deuterium incorporation (>60 examples). The ipso-selectivity of this method provides precise access to libraries of deuterated indoles and quinolines. The synthetic utility of our method has been demonstrated by the incorporation of deuterium into complex natural and drug-like compounds.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/88319, title ="Catalytic Enantioselective Synthesis of Acyclic Quaternary Centers: Palladium-Catalyzed Decarboxylative Allylic Alkylation of Fully Substituted Acyclic Enol Carbonates", author = "Alexy, Eric J. and Zhang, Haiming", journal = "Journal of the American Chemical Society", volume = "140", number = "32", pages = "10109-10112", month = "August", year = "2018", doi = "10.1021/jacs.8b05560", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180727-091530074", note = "© 2018 American Chemical Society. \n\nReceived: May 27, 2018; Published: July 26, 2018. \n\nWe thank NIH-NIGMS (R01GM080269), the Gordon and Betty Moore Foundation, and Caltech for financial support. E.J.A. thanks the National Science Foundation for a predoctoral fellowship. We thank Dr. David VanderVelde (Caltech) for NMR expertise. Dr. Scott Virgil (Caltech) is thanked for instrumentation and SFC assistance. \n\nThe authors declare no competing financial interest.", revision_no = "28", abstract = "The first enantioselective palladium-catalyzed decarboxylative allylic alkylation of fully substituted acyclic enol carbonates providing linear α-quaternary ketones is reported. Investigation into the reaction revealed that the use of an electron-deficient phosphinooxazoline ligand renders the enolate geometry of the starting material inconsequential, with the same enantiomer of product obtained in the same level of selectivity regardless of the starting ratio of enolates. As a result, a general method toward acyclic all-carbon quaternary stereocenters has been developed.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/88573, title ="Synergistic O_3 + OH oxidation pathway to extremely low-volatility dimers revealed in β-pinene secondary organic aerosol", author = "Kenseth, Christopher M. and Huang, Yuanlong", journal = "Proceedings of the National Academy of Sciences of the United States of America", volume = "115", number = "33", pages = "8301-8306", month = "August", year = "2018", doi = "10.1073/pnas.1804671115", issn = "0027-8424", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180803-132305205", note = "© 2018 National Academy of Sciences. Published under the PNAS license. \n\nEdited by Joost A. de Gouw, University of Colorado Boulder, Boulder, CO, and accepted by Editorial Board Member A. R. Ravishankara July 2, 2018 (received for review March 16, 2018). Published ahead of print August 3, 2018. \n\nWe thank Xuan Zhang, John Crounse, and Paul Wennberg for useful discussions. UPLC/(−)ESI-Q-TOF-MS was performed in the Caltech Environmental Analysis Center. This work was supported by National Science Foundation Grants AGS-1523500 and CHE-1508526. R.Z. acknowledges support from a Natural Science and Engineering Research Council of Canada Postdoctoral Fellowship. J.C.H. acknowledges support from the Camille and Henry Dreyfus Postdoctoral Program in Environmental Chemistry. \n\nAuthor contributions: C.M.K. designed research; C.M.K., Y.H., and R.Z. performed research; J.C.H. and B.M.S. contributed new reagents/analytic tools; C.M.K., Y.H., R.Z., and N.F.D. analyzed data; and C.M.K. and J.H.S. wrote the paper. \n\nThis article is a PNAS Direct Submission. J.A.d.G. is a guest editor invited by the Editorial Board. \n\nThe authors declare no conflict of interest. \n\nThis article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1804671115/-/DCSupplemental.", revision_no = "24", abstract = "Dimeric compounds contribute significantly to the formation and growth of atmospheric secondary organic aerosol (SOA) derived from monoterpene oxidation. However, the mechanisms of dimer production, in particular the relevance of gas- vs. particle-phase chemistry, remain unclear. Here, through a combination of mass spectrometric, chromatographic, and synthetic techniques, we identify a suite of dimeric compounds (C_(15–19)H_(24–32)O_(5–11)) formed from concerted O3 and OH oxidation of β-pinene (i.e., accretion of O_3- and OH-derived products/intermediates). These dimers account for an appreciable fraction (5.9–25.4%) of the β-pinene SOA mass and are designated as extremely low-volatility organic compounds. Certain dimers, characterized as covalent dimer esters, are conclusively shown to form through heterogeneous chemistry, while evidence of dimer production via gas-phase reactions is also presented. The formation of dimers through synergistic O_3 + OH oxidation represents a potentially significant, heretofore-unidentified source of low-volatility monoterpene SOA. This reactivity also suggests that the current treatment of SOA formation as a sum of products originating from the isolated oxidation of individual precursors fails to accurately reflect the complexity of oxidation pathways at play in the real atmosphere. Accounting for the role of synergistic oxidation in ambient SOA formation could help to resolve the discrepancy between the measured atmospheric burden of SOA and that predicted by regional air quality and global climate models.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/90766, title ="Cyclic alkanes transfer dehydrogenation using homogeneous iridium pincer catalysts", author = "Al Saihati, Zainab and Haibach, Michael C.", pages = "ENVR-670", month = "August", year = "2018", url = "https://resolver.caltech.edu/CaltechAUTHORS:20181108-143733231", note = "© 2018 American Chemical Society.", revision_no = "10", abstract = "Described herein is a method for the transfer dehydrogenation of cyclic alkanes to alkenes and aroms. using synthesized homogeneous iridium pincer complexes and H_2 acceptor. This method is a promising alternative for the industrial energy intensive dehydrogenation process as iridium pincer catalysts have greater selectivity relative to heterogeneous catalysts and require significantly lower reaction temps.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/88358, title ="Short Enantioselective Formal Synthesis of (–)-Platencin", author = "Defieber, Christian and Mohr, Justin T.", journal = "Synthesis-Stuttgart", volume = "50", number = "22", pages = "4359-4368", month = "July", year = "2018", doi = "10.1055/s-0037-1610437", issn = "0039-7881", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180730-120150815", note = "© 2018 Georg Thieme Verlag Stuttgart.\n\nDedicated to Prof. Dr. Scott E. Denmark on the occasion of his 65th birthday. \n\nWe thank the NIH-NIGMS (R01 GM080269), DAAD (postdoctoral fellowship to C.D.), Eli Lilly (predoctoral fellowship to J.T.M.), Amgen, Bristol-Myers Squibb, Merck Research Laboratories, Abbott Laboratories, Boehringer-Ingelheim, and Caltech for generous funding. We also thank the UIC Department of Chemistry (startup funds to J.T.M.) and the National Science Foundation (CAREER Award 1654490 to J.T.M.).\n\nWe thank Dr. Michael W. Day and Larry Henling for crystallographic analysis.", revision_no = "22", abstract = "A short enantioselective formal synthesis of the antibiotic natural product platencin is reported. Key steps in the synthesis include enantioselective decarboxylation alkylation, aldehyde/olefin radical cyclization, and regioselective aldol cyclization.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/86970, title ="Total Synthesis of the Norhasubanan Alkaloid Stephadiamine", author = "Hartrampf, Nina and Winter, Nils", journal = "Journal of the American Chemical Society", volume = "140", number = "28", pages = "8675-8680", month = "July", year = "2018", doi = "10.1021/jacs.8b01918", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180611-142236882", note = "© 2018 American Chemical Society. \n\nReceived: February 15, 2018; Published: June 11, 2018. \n\nWe acknowledge Dr. Anastasia Hager and Dr. Dominik Hager for their contributions in the early stages of this project. The authors thank Dr. Hong-Dong Hao and Dr. Julius R. Reyes for experimental assistance, Dr. Scott Virgil and René Rahimoff for assistance with HPLC, and Dr. Peter Mayer for X-ray structure analysis. Additionally, we acknowledge the Deutsche Telekom Foundation (Ph.D. fellowship to N.H.), the LMU Mentoring program (fellowship N.H.), the Otto Bayer Scholarship (fellowship to N.H.) as well as the Deutsche Forschungsgemeinschaft (SFB 749 and CIPSM) for generous funding. B.M.S. thanks the NIH-NIGMS (R01GM080269) for partial financial support of this project. Dr. Felix Hartrampf and Dr. Julius R. Reyes are acknowledged for excellent support in the course of this project and with the preparation of this paper.\n\nThe authors declare no competing financial interest.", revision_no = "32", abstract = "(+)-Stephadiamine is an unusual alkaloid isolated from the vine Stephania japonica. It features a norhasubanan skeleton, and contains two adjacent α-tertiary amines, which renders it an attractive synthetic target. Here, we present the first total synthesis of stephadiamine, which hinges on an efficient cascade reaction to implement the aza[4.3.3]propellane core of the alkaloid. The α-aminolactone moiety in a highly hindered position was installed via Tollens reaction and Curtius rearrangement. Useful building blocks for the asymmetric synthesis of morphine and (nor)hasubanan alkaloids are introduced.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/86392, title ="Enantioselective Synthesis of Vicinal All-Carbon Quaternary Centers via Iridium-Catalyzed Allylic Alkylation", author = "Hethcox, J. Caleb and Shockley, Samantha E.", journal = "Angewandte Chemie International Edition", volume = "57", number = "28", pages = "8664-8667", month = "July", year = "2018", doi = "10.1002/anie.201804820", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180514-112203501", note = "© 2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nManuscript received: April 25, 2018; Accepted manuscript online: May 11, 2018; Version of record online: June 11, 2018. \n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for support of our research program. J.C.H. thanks the Camille and Henry Dreyfus postdoctoral program, and S.E.S. thanks the NIH-NIGMS for a predoctoral fellowship (F31GM120804). Dr. Michael Takase and Dr. Lawrence Henling are acknowledge for assistance with X-ray analysis. Dr. Mona Shahgholi and Naseem Torian are thanked for mass spectrometry assistance. Dr. David VanderVelde is thanked for assistance with NMR analysis.", revision_no = "25", abstract = "The development of the first enantioselective transition‐metal‐catalyzed allylic alkylation providing access to acyclic products bearing vicinal all‐carbon quaternary centers is disclosed. The iridium‐catalyzed allylic alkylation reaction proceeds with excellent yields and selectivities for a range of malononitrile‐derived nucleophiles and trisubstituted allylic electrophiles. The utility of these sterically congested products is explored through a series of diverse chemo‐ and diastereoselective product transformations to afford a number of highly valuable, densely functionalized building blocks, including those containing vicinal all‐carbon quaternary stereocenters.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/84082, title ="Wolff/Cope Approach to the AB Ring of the Sesterterpenoid Variecolin", author = "Krout, Michael R. and Henry, Christopher E.", journal = "Journal of Organic Chemistry", volume = "83", number = "13", pages = "6995-7009", month = "July", year = "2018", doi = "10.1021/acs.joc.7b02972", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180104-140230299", note = "© 2018 American Chemical Society. \n\nReceived: November 22, 2017; Published: January 4, 2018. \n\nSpecial Issue: Synthesis of Antibiotics and Related Molecules. \n\nThe authors thank the NIH-NIGMS (R01GM080269), Eli Lilly (predoctoral fellowship to M.R.K.), the Danish Council for Independent Research/Natural Sciences (postdoctoral fellowship to T.J.), Amgen, AbbVie, Bristol-Myers Squibb, Boehringer-Ingelheim, Merck, and Caltech for generous financial support. Dr. Takeharu Toyoshima and Angela Guerrero are acknowledged for contributions to substrate preparation and reaction scouting. Drs. David VanderVelde and Scott Ross of the Caltech NMR facility are thanked for invaluable assistance with NMR experiments and helpful discussions. Lawrence Henling and Michael Day are gratefully acknowledged for X-ray crystallographic structural determination. Dr. Mona Shahgholi and Naseem Torian are acknowledged for assistance with high-resolution mass spectrometry. \n\nThe authors declare no competing financial interest.", revision_no = "27", abstract = "A stereoselective synthesis of the AB ring of the complex sesterterpenoid variecolin is presented. Our strategy features the development of a tandem Wolff/Cope rearrangement of α-diazo cyclobutyl ketones for the construction of fused, 8-membered carbocycles. Preliminary studies revealed a facile Wolff rearrangement but a difficult vinyl ketene cyclobutane Cope rearrangement. We have leveraged an efficient microwave-promoted tandem rearrangement to prepare the desired functionalized cyclooctadienones that we envision as potential key intermediates in the convergent synthesis of variecolin.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/85877, title ="Enantioselective palladium-catalyzed allylic alkylation reactions in the synthesis of Aspidosperma and structurally related monoterpene indole alkaloids", author = "Pritchett, Beau P. and Stoltz, Brian M.", journal = "Natural Product Reports", volume = "35", number = "6", pages = "559-574", month = "June", year = "2018", doi = "10.1039/c7np00069c", issn = "0265-0568", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180416-135313177", note = "© 2018 The Royal Society of Chemistry. \n\nThe article was received on 23 Dec 2017 and first published on 16 Apr 2018. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. B. P. P. thanks the NSF for a predoctoral fellowship (Grant DGE-1144469). Dr Robert Allen Craig, II, is thanked for editorial assistance. \n\nThe authors declare no conflicts of interest.", revision_no = "22", abstract = "Enantioselective Pd-catalyzed allylic alkylations of prochiral enolates represent a powerful tool for the construction of all-carbon quaternary stereocenters. This review describes the emergence of such reactions as strategic linchpins that enable efficient, stereocontrolled syntheses of Aspidosperma and related monoterpene indole alkaloids.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/85462, title ="Development of a Unified Enantioselective, Convergent Synthetic Approach Toward the Furanobutenolide-Derived Polycyclic Norcembranoid Diterpenes: Asymmetric Formation of the Polycyclic Norditerpenoid Carbocyclic Core by Tandem Annulation Cascade", author = "Craig, Robert A., II and Smith, Russell C.", journal = "Journal of Organic Chemistry", volume = "83", number = "7", pages = "3467-3485", month = "April", year = "2018", doi = "10.1021/acs.joc.7b02825", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180327-133635374", note = "© 2018 American Chemical Society. \n\nReceived: December 4, 2017; Published: February 21, 2018. \n\nWe thank the NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support and Eli Lilly & Co. for assistance with biological activity screening. Additionally, we gratefully acknowledge Larry Henling and Dr. Michael Takase (Caltech) for X-ray crystallographic structural determination, Dr. Mona Shahgholi and Naseem Torian (Caltech) for mass spectrometry assistance, and Dr. David VanderVelde (Caltech) for NMR experimental assistance and helpful discussions. Additionally, Prof. Sarah Reisman, Dr. Jeffrey C. Holder, Dr. Corey M. Reeves, Prof. Hosea M. Nelson, Dr. Jonny R. Gordon, Dr. Pamela M. Tadross, and Beau P. Pritchett (Caltech) are thanked for helpful discussions. R.A.C. gratefully acknowledges the support of this work provided by a fellowship from the National Cancer Institute of the National Institutes of Health (NIH) under Award No. F31A17435. J.L.R. thanks the California Tobacco-Related Disease Research Program of the University of California, Grant No. 14DT-0004 for a predoctoral fellowship. A.C.J. thanks the NIH for the support of this work provided by a postdoctoral fellowship (Award No. F32GM082000).", revision_no = "38", abstract = "An enantioselective and diastereoselective approach toward the synthesis of the tetracyclic scaffold of the furanobutenolide-derived polycyclic norditerpenoids is described. Focusing on synthetic efforts toward ineleganolide, the synthetic approach utilizes a palladium-catalyzed enantioselective allylic alkylation for the construction of the requisite chiral tertiary ether. A diastereoselective cyclopropanation–Cope rearrangement cascade enabled the convergent assembly of the ineleganolide [6,7,5,5]-tetracyclic scaffold. Investigation of substrates for this critical tandem annulation process is discussed along with synthetic manipulations of the [6,7,5,5]-tetracyclic scaffold and the attempted interconversion of the [6,7,5,5]-tetracyclic scaffold of ineleganolide to the isomeric [7,6,5,5]-core of scabrolide A and its naturally occurring isomers. Computational evaluation of ground-state energies of late-stage synthetic intermediates was used to guide synthetic development and aid in the investigation of the conformational rigidity of these highly constrained and compact polycyclic structures.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/84197, title ="The Cyanthiwigin Natural Product Core as a Complex Molecular Scaffold for Comparative Late-Stage C–H Functionalization Studies", author = "Kim, Kelly E. and Adams, Ashley M.", journal = "Journal of Organic Chemistry", volume = "83", number = "6", pages = "3023-3033", month = "March", year = "2018", doi = "10.1021/acs.joc.7b03291", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180109-144403638", note = "© 2018 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: December 29, 2017; Published: January 9, 2018. \n\nThis work was supported by the NSF under the CCI Center for Selective C–H Functionalization (CCHF), CHE-1700982. Additional financial support was provided by Caltech and Novartis. Dr. Xiangyou Xing and members of the CCHF are acknowledged for helpful discussions. The White group (UIUC) and the Sarpong group (UC Berkeley) are thanked for supplying the Fe(R,R-CF3-PDP) and Fe(S,S-PDP) catalysts, respectively. Dr. David VanderVelde (NMR), Dr. Mona Shahgholi and Naseem Torian (HRMS), and Dr. Michael K. Takase and Niklas Thompson (X-ray crystallography) are acknowledged for assistance with structural determination and characterization. \n\nThe authors declare no competing financial interest.", revision_no = "24", abstract = "The desire for maximally efficient transformations in complex molecule synthesis has contributed to a surge of interest in C–H functionalization methods development in recent years. In contrast to the steady stream of methodological reports, however, there are noticeably fewer studies comparing the efficacies of different C–H functionalization protocols on a single structurally intricate substrate. Recognizing the importance of heteroatom incorporation in complex molecule synthesis, this report discloses a comparative examination of diverse strategies for C–O, C–N, and C–X bond formation through late-stage C–H oxidation of the tricyclic cyanthiwigin natural product core. Methods for allylic C–H acetoxylation, tertiary C–H hydroxylation, tertiary C–H amination, tertiary C–H azidation, and secondary C–H halogenation are explored. These efforts highlight the robustness and selectivities of many well-established protocols for C–H oxidation when applied to a complex molecular framework, and the findings are relevant to chemists aiming to employ such strategies in the context of chemical synthesis.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/84705, title ="Nickel-catalyzed enantioselective allylic alkylation of lactones and lactams with unactivated allylic alcohols", author = "Ngamnithiporn, Aurapat and Jette, Carina I.", journal = "Chemical Science", volume = "2018", number = "9", pages = "2547-2551", month = "March", year = "2018", doi = "10.1039/c7sc05216b", issn = "2041-6520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180207-083556564", note = "© 2018 The Royal Society of Chemistry. This Open Access Article is licensed under a Creative Commons Attribution 3.0 Unported Licence. \n\nReceived 8th December 2017 , Accepted 12th January 2018. First published on 24th January 2018. \n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for support of our research program. A. N. thanks the Royal Thai Government Scholarship program. C. I. J. thanks the National Science Foundation for a predoctoral fellowship. Dr Michael Takase (Caltech) is acknowledged for assistance with X-ray analysis. We thank Dr Mona Shahgholi (Caltech) for mass spectrometry assistance. \n\nThere are no conflicts to declare.", revision_no = "23", abstract = "The first nickel-catalyzed enantioselective allylic alkylation of lactone and lactam substrates to deliver products bearing an all-carbon quaternary stereocenter is reported. The reaction, which utilizes a commercially available chiral bisphosphine ligand, proceeds in good yield with a high level of enantioselectivity (up to 90% ee) on a range of unactivated allylic alcohols for both lactone and lactam nucleophiles. The utility of this method is further highlighted via a number of synthetically useful product transformations.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/85813, title ="Award Address (ACS Award for Creative Work in Synthetic Organic Chemistry sponsored by MilliporeSigma). Complex natural products as a driving force for discovery in organic chemistry", author = "Stoltz, Brian", pages = "ORGN-524", month = "March", year = "2018", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180413-085522795", note = "© 2018 American Chemical Society.", revision_no = "10", abstract = "Our lab. is deeply interested in the discovery and development of new reaction methodol. en route to the chem. synthesis of\ncomplex bioactive mols. Over the course of the past seventeen years, research in our group at the California Institute of\nTechnol. has been initiated in the general area of synthetic chem., with a focus on the development of new strategies for the prepn. of complex mols., including natural products that possess interesting structural, biol., and phys. properties. Concurrent to this program of target driven synthesis is a strong effort directed toward the development of new techniques and reaction methods, which are useful for a range of applications. Typically, the complex target structure is used as an inspiration for the discovery of new reactions and technologies that may eventually be regarded as general synthetic methodol. Consequently, this approach provides access to (a) novel, medicinally relevant structures, (b) a general method for their synthesis, and (c) new synthetic methods that will be beneficial for a host of applications. Thus, In the process of completing the synthesis of a range of important compds., we have developed a no. of new methods that enabled their access. These topics will be\ndiscussed in the lecture.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/87797, title ="Total synthesis of (±)-phomoidride D: A 22 year odyssey", author = "Leung, Joyce and Bederman, Aaron", pages = "ORGN-521", month = "March", year = "2018", url = "https://resolver.caltech.edu/CaltechAUTHORS:20180712-081511897", note = "© 2018 American Chemical Society.", revision_no = "12", abstract = "Recent efforts in our labs. have culminated in a completed synthesis of the phomoidride D via a strategy that evolved over a 22-yr period. The evolution of this strategies will be discussed.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/102553, title ="Total Synthesis of (±)-Phomoidride\u2005D", author = "Leung, Joyce C. and Bedermann, Aaron A.", journal = "Angewandte Chemie International Edition", volume = "57", number = "7", pages = "1991-1994", month = "February", year = "2018", doi = "10.1002/anie.201712369", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20200415-101219737", note = "© 2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nIssue Online: 06 February 2018; Version of Record online: 17 January 2018; Accepted manuscript online: 29 December 2017; Manuscript received: 02 December 2017. \n\nThe authors gratefully acknowledge support of this work from Bristol‐Myers Squibb, Eli Lilly, Glaxo‐Wellcome, Yamanouchi (now Astellas), AstraZeneca, and Amgen through their faculty award programs, and the Camille and Henry Dreyfus Foundation for a Teacher Scholar Award to J.W. J.T.N. thanks the Helgu and Jónsdóttur and Sigurliða Kristjánsson Memorial Foundation, G.K.M. thanks the NSERC of Canada, T.S. thanks Prof. Satoshi Ōmura and the Kitasato Institute, and N.T. thanks Yamanouchi (now Astellas). The authors thank Prof. Kevin Klausmeyer and Ms. Sam Yruegas for obtaining and analyzing X‐ray crystallographic data. We also gratefully acknowledge financial support from Baylor University, the Welch Foundation (Chair, AA‐006), and the Cancer Prevention and Research Institute of Texas (CPRIT, R1309). \n\nThe authors declare no conflict of interest.", revision_no = "12", abstract = "Described herein is a synthetic strategy for the total synthesis of (±)‐phomoidride\u2005D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels–Alder cycloaddition. A subsequent SmI2‐mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/81215, title ="Progress towards the total synthesis of hamigerans C and D: a direct approach to an elaborated 6-7-5 carbocyclic core", author = "Duquette, Douglas Charles and Jensen, Thomas", journal = "Journal of Antibiotics", volume = "71", number = "2", pages = "263-267", month = "February", year = "2018", doi = "10.1038/ja.2017.96", issn = "0021-8820", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170906-153516673", note = "© 2017 Japan Antibiotics Research Association. \n\nReceived 8 June 2017; revised 3 July 2017; accepted 6 July 2017. Online publication, 6 September 2017. \n\nDedicated to Prof K. C. Nicolaou for his tremendous scientific contributions to the total synthesis of highly complex and biologically important natural products. We thank NIH-NIGMS (R01GM080269) for supporting this research. DCD would like to thank the NSF (predoctoral research fellowship, No. DGE-1144469) and Caltech for financial support. Dr David VanderVelde (Caltech) is thanked for aid in NMR structural determination. Dr Allen Hong and Dr Scott Virgil are thanked for helpful discussions. \n\nThe authors declare no conflict of interest.", revision_no = "23", abstract = "The hamigeran family of natural products has been the target of numerous synthetic efforts because of its biological activity and interesting structural properties. Herein, we disclose our efforts toward the synthesis of hamigerans C and D, unique among the initially isolated members because of their 6-7-5 carbocyclic core. Our approach directly targets this tricyclic motif by sequential Negishi and Heck coupling reactions, yielding an advanced intermediate with all necessary carbons and sufficient functionality poised for completion of the synthesis of these two natural products.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/83562, title ="Isocanthine Synthesis via Rh(III)-Catalyzed Intramolecular C-H Functionalization", author = "Chen, Anthony Y. and Lu, Qianqian", journal = "Journal of Organic Chemistry", volume = "83", number = "1", pages = "330-337", month = "January", year = "2018", doi = "10.1021/acs.joc.7b02731", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20171129-075958117", note = "© 2017 American Chemical Society. \n\nReceived: October 27, 2017; Published: November 28, 2017. \n\nThis paper is dedicated to Professor Richard C. Larock, Emeritus Professor of Chemistry at Iowa State University on the occasion of his 73rd birthday. The authors would like to thank Dr. Kevin Kou (University of California, Berkeley) for helpful discussion, Dr. Kenji Kurita (Genentech, Inc.) for collecting HRMS data, Mr. Malcolm Huestis (Genentech, Inc.) for providing catalyst C1, and Dr. Francis Gosselin (Genentech, Inc.) for proof-reading the manuscript. AYC, RS and BMS are grateful to the NSF under the CCI Center for Selective C–H Functionalization (CHE-1205646 and CHE-1700982) for support. Part of this research was presented in the Symposium of Applications of C–H Functionalization, Pacifichem, Honolulu, HI in December, 2015. AYC was an undergraduate summer intern at Genentech, Inc. where this work was initiated. \n\nThe authors declare no competing financial interest.", revision_no = "22", abstract = "An efficient synthesis of substituted isocanthines has been achieved using an intramolecular Rh(III)-catalyzed C–H functionalization of alkyne-tethered indoles in the presence of catalytic tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate and stoichiometric copper(II) acetate. This isocanthine synthesis tolerates a variety of electronically diverse 5- or 6-substituted indoles with N-tethered alkyne coupling partners and can also be extended to pyrrole derivatives for the synthesis of annulated 5-azaindoles.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/83952, title ="Atmospheric autoxidation is increasingly important in urban and suburban North America", author = "Praske, Eric and Otkjær, Rasmus V.", journal = "Proceedings of the National Academy of Sciences of the United States of America", volume = "115", number = "1", pages = "64-69", month = "January", year = "2018", doi = "10.1073/pnas.1715540115 ", issn = "0027-8424", url = "https://resolver.caltech.edu/CaltechAUTHORS:20171219-073339592", note = "© 2017 National Academy of Sciences. Published under the PNAS license. \n\nEdited by Marsha I. Lester, University of Pennsylvania, Philadelphia, PA, and approved November 8, 2017 (received for review September 7, 2017). Published online before print December 18, 2017. \n\nWe thank Kristian H. Møller for helpful discussions related to the implementation of MC-TST. J.C.H. thanks the Camille and Henry Dreyfus Postdoctoral Program in Environmental Chemistry for support. We acknowledge funding from National Science Foundation Grant CHE-1508526 as well as from the University of Copenhagen. \n\nAuthor contributions: J.D.C., H.G.K., and P.O.W. designed research; E.P., R.V.O., J.D.C., and H.G.K. performed research; J.C.H., B.M.S., and P.O.W. contributed new reagents/analytic tools; E.P., R.V.O., and J.D.C. analyzed data; and E.P., R.V.O., J.D.C., H.G.K., and P.O.W. wrote the paper. \n\nThe authors declare no conflict of interest. \n\nThis article is a PNAS Direct Submission. \n \nThis article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1715540115/-/DCSupplemental.", revision_no = "23", abstract = "Gas-phase autoxidation—regenerative peroxy radical formation following intramolecular hydrogen shifts—is known to be important in the combustion of organic materials. The relevance of this chemistry in the oxidation of organics in the atmosphere has received less attention due, in part, to the lack of kinetic data at relevant temperatures. Here, we combine computational and experimental approaches to investigate the rate of autoxidation for organic peroxy radicals (RO_2) produced in the oxidation of a prototypical atmospheric pollutant, n-hexane. We find that the reaction rate depends critically on the molecular configuration of the RO_2 radical undergoing hydrogen transfer (H-shift). RO_2 H-shift rate coefficients via transition states involving six- and seven-membered rings (1,5 and 1,6 H-shifts, respectively) of α-OH hydrogens (HOC-H) formed in this system are of order 0.1 s^(−1) at 296 K, while the 1,4 H-shift is calculated to be orders of magnitude slower. Consistent with H-shift reactions over a substantial energetic barrier, we find that the rate coefficients of these reactions increase rapidly with temperature and exhibit a large, primary, kinetic isotope effect. The observed H-shift rate coefficients are sufficiently fast that, as a result of ongoing NO_x emission reductions, autoxidation is now competing with bimolecular chemistry even in the most polluted North American cities, particularly during summer afternoons when NO levels are low and temperatures are elevated.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/83027, title ="Model Studies to Access the [6,7,5,5]-Core of Ineleganolide Using Tandem Translactonization-Cope or Cyclopropanation-Cope Rearrangements as Key Steps", author = "Roizen, Jennifer L. and Jones, Amanda C.", journal = "Journal of Organic Chemistry", volume = "82", number = "24", pages = "13051-13067", month = "December", year = "2017", doi = "10.1021/acs.joc.7b02030", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20171107-103337734", note = "© 2017 American Chemical Society. \n\nReceived: August 11, 2017; Published: November 7, 2017. \n\nThe authors wish to thank the NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. Additionally, the authors gratefully acknowledge Larry Henling and the late Dr. Michael Day (Caltech) for X-ray crystallographic structural determination; Dr. Mona Shahgholi and Naseem Torian (Caltech) for mass spectrometric analysis; Dr. David VanderVelde (Caltech) for NMR experimental assistance and helpful discussions; Dr. Masaki Seto, Dr. N. Sherden, and Dr. D. E. White for helpful discussions; and Dr. R. A. Craig, II for editorial suggestions. J.L.R. thanks the California Tobacco-Related Disease Research Program of the University of California, Grant Number 14DT-0004 for a predoctoral fellowship. A.C.J. thanks the NIH (F32GM082000) for a postdoctoral fellowship. \n\nThe authors declare no competing financial interest.", revision_no = "26", abstract = "Recently, we reported a convergent cyclopropanation–Cope approach to the core of ineleganolide, which was the first disclosed synthesis of the core of the norditerpene natural product ineleganolide. In this complementary work, a model system for the core of ineleganolide has been prepared through a series of tandem cyclopropanation–Cope and translactonization–Cope rearrangements. Work with this model system has enriched our understanding of the cyclopropanation–Cope rearrangement sequence. Additionally, research into this model system has driven the development of tandem translactonization–Cope rearrangements.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/82077, title ="Catalytic Reduction of Alkyl and Aryl Bromides Using Propan-2-ol", author = "Haibach, Michael C. and Stoltz, Brian M.", journal = "Angewandte Chemie International Edition", volume = "56", number = "47", pages = "15123-15126", month = "November", year = "2017", doi = "10.1002/anie.201708800", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20171004-144313124", note = "© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nManuscript received: August 25, 2017; Accepted manuscript online: October 3, 2017; Version of record online: October 24, 2017.\n\nWe acknowledge funding from King Fahd University of Petroleum and Minerals. M.C.H. acknowledges funding from the Resnick Sustainability Institute in the form of a postdoctral fellowship. \n\nThe authors declare no conflict of interest.", revision_no = "31", abstract = "Milstein's complex, (PNN)RuHCl(CO), catalyzes the efficient reduction of aryl and alkyl halides under relatively mild conditions by using propan-2-ol and a base. Sterically hindered tertiary and neopentyl substrates are reduced efficiently, as well as more functionalized aryl and alkyl bromides. The reduction process is proposed to occur by radical abstraction/hydrodehalogenation steps at ruthenium. Our research represents a safer and more sustainable alternative to typical silane, lithium aluminium hydride, and tin-based conditions for these reductions.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/81444, title ="Enantioselective Pd-Catalyzed Decarboxylative Allylic Alkylation of Thiopyranones. Access to Acyclic, Stereogenic α-Quaternary Ketones", author = "Alexy, Eric J. and Virgil, Scott C.", journal = "Organic Letters", volume = "19", number = "19", pages = "5007-5009", month = "October", year = "2017", doi = "10.1021/acs.orglett.7b02354", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170914-131404458", note = "© 2017 American Chemical Society. \n\nReceived: July 30, 2017; Published: September 13, 2017. \n\nWe thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. E.J.A. is grateful to the National Science Foundation for a predoctoral fellowship. We thank Dr. David VanderVelde (Caltech) for NMR expertise, and Dr. Mona Shahgholi (Caltech) and Naseem Torian (Caltech) for mass spectrometry assistance. \n\nThe authors declare no competing financial interest.", revision_no = "26", abstract = "A catalytic, enantioselective decarboxylative allylic alkylation of 4-thiopyranones is reported. The α-quaternary 4-thiopyranones produced are challenging to access by standard enolate alkylation owing to facile ring-opening β-sulfur elimination. In addition, reduction of the carbon–sulfur bonds provides access to elusive acyclic α-quaternary ketones. The alkylated products are obtained in up to 92% yield and 94% enantiomeric excess.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/81521, title ="Sequential Ruthenium Catalysis for Olefin Isomerization and Oxidation: Application to the Synthesis of Unusual Amino Acids", author = "Liniger, Marc and Liu, Yiyang", journal = "Journal of the American Chemical Society", volume = "139", number = "39", pages = "13944-13949", month = "October", year = "2017", doi = "10.1021/jacs.7b08496", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170918-101644915", note = "© 2017 American Chemical Society. \n\nReceived: August 10, 2017; Published: September 16, 2017.\n\nDedicated to Professor Albert Padwa on the occasion of his 80th birthday. The authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. M.L. thanks the Swiss National Science Foundation (SNSF) for a postdoctoral fellowship (P2EZP2_148751). Dr. Scott Virgil and the Caltech Center for Catalysis and Chemical Synthesis are acknowledged for the generous donation of catalyst 2 and Materia Inc. for the donation of catalyst 1a. The authors thank Dr. Michael Takase and Larry Henling for X-ray structural determinations. The Hsieh-Wilson group is acknowledged for nanopure water and the Dougherty group for using their freeze-drying equipment. Lukas Hilpert, Kyle Virgil, and Katerina Korch are thanked for experimental assistance. Dr. Beau P. Pritchett is gratefully acknowledged for recording analytical data and for proofreading the manuscript.\n\nThe authors declare no competing financial interest.", revision_no = "43", abstract = "How can you use a ruthenium isomerization catalyst twice? A ruthenium-catalyzed sequence for the formal two-carbon scission of allyl groups to carboxylic acids has been developed. The reaction includes an initial isomerization step using commercially available ruthenium catalysts followed by in situ transformation of the complex to a metal-oxo species, which is capable of catalyzing subsequent oxidation reactions. The method enables enantioselective syntheses of challenging α-tri- and tetrasubstituted α-amino acids including an expedient total synthesis of the antiepileptic drug levetiracetam.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/81144, title ="Enantioselective Catalysis Coupled with Stereodivergent Cyclization Strategies Enables Rapid Syntheses of (+)-Limaspermidine and (+)-Kopsihainanine A", author = "Pritchett, Beau P. and Donckele, Etienne J.", journal = "Angewandte Chemie International Edition", volume = "56", number = "41", pages = "12624-12627", month = "October", year = "2017", doi = "10.1002/anie.201707304", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170905-134054944", note = "© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nIssue online: 27 September 2017; Version of record online: \n5 September 2017; Manuscript Received: 18 July 2017. \n\n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support. B.P.P. thanks the NSF for a predoctoral fellowship (Grant DGE-1144469). E.J.D. thanks the Swiss National Science Foundation (SNSF) for a postdoctoral fellowship (Grant P2EZP2_168798). The authors thank Dr. Mona Shahgholi and Naseem Torian (Caltech) for mass spectrometry assistance, Dr. Scott Virgil (Caltech) for instrumentation assistance, and Larry Henling (Caltech) for X-ray crystallographic assistance. \n\nThe authors declare no conflict of interest.", revision_no = "28", abstract = "Enantioselective Pd-catalyzed allylic alkylations of dihydropyrido[1,2-a]indolone (DHPI) substrates were used to construct the C20-quaternary stereocenters of multiple monoterpene indole alkaloids. Stereodivergent Pictet–Spengler and Bischler–Napieralski cyclization/reduction cascades furnish the cis- and trans-fused azadecalin subunits present in Aspidosperma and Kopsia alkaloids, respectively, en\u2005route to highly efficient syntheses of (+)-limaspermidine and (+)-kopsihainanine\u2005A.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/79196, title ="Enantioselective Synthesis of Acyclic α-Quaternary Carboxylic Acid Derivatives through Iridium-Catalyzed Allylic Alkylation", author = "Shockley, Samantha E. and Hethcox, J. Caleb", journal = "Angewandte Chemie International Edition", volume = "56", number = "38", pages = "11545-11548", month = "September", year = "2017", doi = "10.1002/anie.201707015", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170719-091950600", note = "© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nManuscript received: July 10, 2017; Accepted manuscript online: July 19, 2017; Version of record online: August 9, 2017.\n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for\nsupport of our research program. J.C.H. thanks the Camille and Henry Dreyfus postdoctoral program, and S.E.S. thanks the NIH-NIGMS for a predoctoral fellowship (F31GM120804). Dr. Michael Takase, Dr. Lawrence Henling, and Niklas Thompson are acknowledged for assistance with X-ray analysis. Dr. Mona Shahgholi and Naseem Torian are thanked for mass spectrometry assistance. Dr. Scott Virgil is thanked for assistance with instrumentation. \n\nThe authors declare no conflict of interest.", revision_no = "36", abstract = "The first highly enantioselective iridium-catalyzed allylic alkylation providing access to products bearing an allylic all-carbon quaternary stereogenic center has been developed. The reaction utilizes a masked acyl cyanide (MAC) reagent, which enables the one-pot preparation of α-quaternary carboxylic acids, esters, and amides with a high degree of enantioselectivity. The utility of these products is further explored via a series of diverse product transformations.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/78843, title ="Asymmetric Synthesis of All-Carbon Quaternary Spirocycles via a Catalytic Enantioselective Allylic Alkylation Strategy", author = "Shockley, Samantha E. and Hethcox, J. Caleb", journal = "Tetrahedron Letters", volume = "58", number = "34", pages = "3341-3343", month = "August", year = "2017", doi = "10.1016/j.tetlet.2017.07.022", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170707-100417876", note = "© 2017 Elsevier Ltd. \n\nReceived 27 June 2017, Accepted 3 July 2017, Available online 5 July 2017. \n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for support of our research program. J.C.H. thanks the Camille and Henry Dreyfus postdoctoral program, and S.E.S. thanks the NIH-NIGMS for a predoctoral fellowship (F31GM120804). Dr. Mona Shahgholi and Naseem Torian (Caltech) are thanked for mass spectrometry assistance. Dr. Scott Virgil (Caltech) is thanked for assistance with instrumentation.", revision_no = "24", abstract = "Rapid access to enantioenriched spirocycles possessing a 1,4-dicarbonyl moiety spanning an all-carbon quaternary stereogenic spirocenter was achieved using a masked bromomethyl vinyl ketone reagent. The developed protocol entails an enantioselective palladium-catalyzed allylic alkylation reaction followed by a one-pot unmasking/RCM sequence that provides access to the spirocyclic compounds in good yields and selectivities.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/79248, title ="Enantioselective Total Synthesis of Nigelladine A via Late-Stage C–H Oxidation Enabled by an Engineered P450 Enzyme", author = "Loskot, Steven A. and Romney, David K.", journal = "Journal of the American Chemical Society", volume = "139", number = "30", pages = "10196-10199", month = "August", year = "2017", doi = "10.1021/jacs.7b05196", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170720-100846797", note = "© 2017 American Chemical Society. \n\nReceived: May 19, 2017; Published: July 19, 2017. \n\nThis work was supported by the NSF under the CCI Center for Selective C–H Functionalization (CHE-1205646). D.K.R. was supported by a Ruth Kirschstein NIH Postdoctoral Fellowship (F32GM117635). Additional financial support was provided by Caltech and Novartis. We thank Dr. Scott Virgil (CIT) and the Caltech 3CS for access to analytical equipment. The authors gratefully acknowledge Larry Henling and Dr. Michael Takase (CIT) for X-ray crystallographic structural determination, Dr. Mona Shahgholi and Naseem Torian (CIT) for mass spectrometry assistance, and Dr. David VanderVelde (CIT) for NMR experimental assistance and helpful discussions. The authors also acknowledge Dr. Sabine Brinkmann-Chen and Dr. Stephan Hammer (CIT) for helpful discussions regarding the enzymatic oxidation system.", revision_no = "29", abstract = "An enantioselective total synthesis of the norditerpenoid alkaloid nigelladine A is described. Strategically, the synthesis relies on a late-stage C–H oxidation of an advanced intermediate. While traditional chemical methods failed to deliver the desired outcome, an engineered cytochrome P450 enzyme was employed to effect a chemo- and regioselective allylic C–H oxidation in the presence of four oxidizable positions. The enzyme variant was readily identified from a focused library of three enzymes, allowing for completion of the synthesis without the need for extensive screening.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/81399, title ="Recent developments in stereoselective iridium-catalyzed allylic alkylation methodologies", author = "Shockley, Samantha and Hethcox, Caleb", pages = "WCC-9", month = "August", year = "2017", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170913-084235803", note = "© 2017 American Chemical Society.", revision_no = "9", abstract = "We report our ongoing studies in the field of iridium-catalyzed allylic alkylation chem. The first regio-,\ndiastereo-, and enantioselective transition-metal-catalyzed allylic alkylation reaction forming vicinal tertiary\nand all-carbon quaternary stereocenters between prochiral enolates and an aliph.-substituted electrophile is\ndisclosed. Crit. to the success of this new reaction is the identity and ubiquity of the chloride counterion in\naddn. to the use of proton sponge, the combination of which affords excellent regio- and enantioselectivities along with good yields and diastereoselectivities. Addnl., a no. of transformations were carried out on the alkylation products to demonstrate the value of this method in rapidly accessing highly functionalized, stereochem. rich polycyclic scaffolds. Further exploration of this chem. has continued to expand the scope of these types of transformations with respect to the nucleophile and electrophile. Our recent efforts in this field will be discussed.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/81569, title ="Twists and turns of lactam research", author = "Stoltz, Brian M.", pages = "ORGN-202", month = "August", year = "2017", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170919-130910278", note = "© 2017 American Chemical Society.", revision_no = "9", abstract = "The importance of the amide bond cannot be overstated. Typical amides are planar structures, however, amide\nbonds can be highly twisted such as in bicyclic bridgehead lactams. The distortion of the orbitals from planarity\nand the pyramidalization of the nitrogen from sp toward sp dramatically affect the stability and reactivity of\nanti-Bredt amides. In 2006, our group published the first unambiguous synthesis and characterization of 2-\nquinuclidonium tetrafluoroborate. Since then we have been fascinated with the synthesis and characterization\nof such strained reactive lactams. We have also pursued the synthesis of a series of novel stereogenic lactams\nthat can be employed as intermediates in multi-step synthesis. The lecture will discuss our efforts in these\nvibrant research areas. Looking ahead, the limits are still open for the synthesis of more or less reactive but\nstructurally unique and often twisted amides.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/78510, title ="Enantioselective Construction of Acyclic Quaternary Carbon Stereocenters: Palladium-Catalyzed Decarboxylative Allylic Alkylation of Fully-Substituted Amide Enolates", author = "Starkov, Pavel and Moore, Jared T.", journal = "Journal of the American Chemical Society", volume = "139", number = "28", pages = "9615-9620", month = "July", year = "2017", doi = "10.1021/jacs.7b04086", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170623-095559709", note = "© 2017 American Chemical Society. \n\nReceived: April 22, 2017; Published: June 19, 2017. \n\nThis research was supported by the Israel Science Foundation administrated by the Israel Academy of Sciences and Humanities (140/12), the Fund for Promotion of Research at the Technion, the NIH-NIGMS (R01GM080269), and the NSF (predoctoral research fellowship to D.C.D., No. DGE-1144469). Research reported in this publication was supported by the NIH-NIGMS under Award Number F32GM116304 (postdoctoral fellowship to J.T.M.). I.M. is holder of the Sir Michael and Lady Sobell Academic Chair (Technion). Dr. Mona Shahgholi (Caltech) and Naseem Torian (Caltech) are thanked for mass spectrometry assistance. Dr. Scott Virgil (Caltech) is thanked for instrumentation assistance and helpful discussions. \n\nThe authors declare no competing financial interest.", revision_no = "31", abstract = "We report a divergent and modular protocol for the preparation of acyclic molecular frameworks containing newly created quaternary carbon stereocenters. Central to this approach is a sequence composed of a (1) regioselective and -retentive preparation of allyloxycarbonyl-trapped fully substituted stereodefined amide enolates and of a (2) enantioselective palladium-catalyzed decarboxylative allylic alkylation reaction using a novel bisphosphine ligand.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/77601, title ="Polycyclic Furanobutenolide-Derived Cembranoid and Norcembranoid Natural Products: Biosynthetic Connections and Synthetic Efforts", author = "Craig, Robert A., II and Stoltz, Brian M.", journal = "Chemical Reviews", volume = "117", number = "12", pages = "7878-7909", month = "June", year = "2017", doi = "10.1021/acs.chemrev.7b00083", issn = "0009-2665", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170519-105858158", note = "© 2017 American Chemical Society. \n\nReceived: February 7, 2017; Published: May 18, 2017. \n\nThe authors thank the NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. R.A.C. gratefully acknowledges the support of this work provided by a fellowship from the National Cancer Institute of the National Institutes of Health (NIH) under Award F31A17435. Dr. Corey Reeves (Caltech), Dr. Aaron Bedell (Stanford), and Mr. James B. C. Mack (Stanford) are also thanked for editorial assistance. Additionally, the authors thank all of the collaborators and co-workers who have contributed to the synthetic efforts toward ineleganolide and the polycyclic furanobutenolide-derived norcembranoids at Caltech for thoughtful insights and acknowledge helpful discussions including Prof. Jennifer L. Roizen, Dr. Russell C. Smith, Prof. Amanda C. Jones, Dr. Scott C. Virgil, Mr. Beau P. Pritchett, Mr. Benzi I. Estipona, Dr. Seo-Jung Han, Prof. Amanda Silberstein, Mr. Chris Reimann, and Dr. David Romney.", revision_no = "23", abstract = "The polycyclic furanobutenolide-derived cembranoid and norcembranoid natural products are a family of congested, stereochemically complex, and extensively oxygenated polycyclic diterpenes and norditerpenes. Although the elegant architectures and biological activity profiles of these natural products have captured the attention of chemists since the isolation of the first members of the family in the 1990s, the de novo synthesis of only a single polycyclic furanobutenolide-derived cembranoid and norcembranoid has been accomplished. This article begins with a brief discussion of the proposed biosyntheses and biosynthetic connections among the polycyclic furanobutenolide-derived cembranoids and norcembranoids and then provides a comprehensive review of the synthetic efforts toward each member of the natural product family, including biomimetic, semisynthetic, and de novo synthetic strategies. This body of knowledge has been gathered to provide insight into the reactivity and constraints of these compact and highly oxygenated polycyclic structures, as well as to offer guidance for future synthetic endeavors.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/77127, title ="Ionic and Neutral Mechanisms for C–H Bond Silylation of Aromatic Heterocycles Catalyzed by Potassium t-Butoxide", author = "Banerjee, Shibdas and Yang, Yun-Fang", journal = "Journal of the American Chemical Society", volume = "139", number = "20", pages = "6880-6887", month = "May", year = "2017", doi = "10.1021/jacs.6b13032", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170502-104649589", note = "© 2017 American Chemical Society. \n\nReceived: December 19, 2016; Published: May 2, 2017.\n\nAuthors thank N. Dalleska (Caltech), R. Pfattner (Stanford), and M. R. Angell (Stanford) for their help. This work was supported by National Science Foundation under the CCI Center for Selective C–H Functionalization (CHE-1205646 and CHE-1361104), Air Force Office of Scientific Research through Basic Research Initiative grant (AFOSR FA9550-16-1-0113), and the Australian Research Council (FT120100632 to EHK). Calculations were performed on the Hoffman2 cluster at UCLA and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF, and the National Facility of the Australian National Computational Infrastructure.", revision_no = "20", abstract = "Exploiting C–H bond activation is difficult, although some success has been achieved using precious metal catalysts. Recently, it was reported that C–H bonds in aromatic heterocycles were converted to C–Si bonds by reaction with hydrosilanes under the catalytic action of potassium t-butoxide alone. The use of Earth-abundant potassium cation as a catalyst for C–H bond functionalization seems to be without precedent, and no mechanism for the process was established. Using ambient ionization mass spectrometry, we are able to identify crucial ionic intermediates present during the C–H silylation reaction. We propose a plausible catalytic cycle, which involves a pentacoordinate silicon intermediate consisting of silane reagent, substrate, and the t-butoxide catalyst. Heterolysis of the Si–H bond, deprotonation of the heteroarene, addition of the heteroarene carbanion to the silylether, and dissociation of t-butoxide from silicon lead to the silylated heteroarene product. The steps of the silylation mechanism may follow either an ionic route involving K^+ and tBuO^– ions or a neutral heterolytic route involving the [KOtBu]_4 tetramer. Both mechanisms are consistent with the ionic intermediates detected experimentally. We also present reasons why potassium t-butoxide is an active catalyst whereas sodium t-butoxide and lithium t-butoxide are not, and we explain the relative reactivities of different (hetero)arenes in the silylation reaction. The unique role of potassium t-butoxide is traced, in part, to the stabilization of crucial intermediates through cation-π interactions.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/76553, title ="Potassium tert-Butoxide-Catalyzed Dehydrogenative C–H Silylation of Heteroaromatics: A Combined Experimental and Computational Mechanistic Study", author = "Liu, Wen-Bo and Schuman, David P.", journal = "Journal of the American Chemical Society", volume = "139", number = "20", pages = "6867-6879", month = "May", year = "2017", doi = "10.1021/jacs.6b13031", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170413-121146154", note = "© 2017 American Chemical Society. \n\nReceived 19 December 2016. Published online 12 April 2017. \n\nThe authors wish to thank the NSF under the CCI Center for Selective C–H Functionalization (CCHF) (CHE-1205646), CHE-\n1212767 for support, the Novartis Institutes for Biomedical Research Incorporated for the donation of samples to the CCHF, and CHE-1361104. Calculations were performed on the Hoffman2 cluster at UCLA and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF. The Shanghai Institute of Organic Chemistry (SIOC) and S.-L. You are thanked for a postdoctoral fellowship to W.-B.L. D.P.S. thanks the CCI Center for Selective C–H Functionalization for support and the Blackmond group (TSRI) for their assistance and hospitality. A.A.T. is grateful to Bristol-Myers Squibb, the Resnick Sustainability Institute at Caltech, and to Dow Chemical for predoctoral fellowship as well as to NSERC for a PGS D fellowship. M.O. is indebted to the Einstein Foundation (Berlin) for an endowed professorship. N.N. thanks Florida Tech for sabbatical leave and thanks B.M.S. and Caltech for hosting him in their research labs. We thank J. Buss (Caltech), N. Thompson (Caltech), Prof. Krenske (University of Queensland), and Prof. Jenkins (Griffith Univ.) for helpful discussions. The Peters, Bercaw, and Agapie groups (Caltech) are thanked for instrumentation. We thank Dr. Angelo Di Bilio for assistance in recording EPR spectra, Dr. Dave VanderVelde for NMR expertise, and Dr. Mona Shahgholi and Dr. Naseem Torian for mass spectrometry assistance (Caltech). We thank Claude Y. Legault for CYLView, used for the molecular graphics. \n\nThe authors declare no competing financial interest.", revision_no = "28", abstract = "We recently reported a new method for the direct dehydrogenative C–H silylation of heteroaromatics utilizing Earth-abundant potassium tert-butoxide. Herein we report a systematic experimental and computational mechanistic investigation of this transformation. Our experimental results are consistent with a radical chain mechanism. A trialkylsilyl radical may be initially generated by homolytic cleavage of a weakened Si–H bond of a hypercoordinated silicon species as detected by IR, or by traces of oxygen which can generate a reactive peroxide by reaction with (KOt-Bu)_4 as indicated by density functional theory (DFT) calculations. Radical clock and kinetic isotope experiments support a mechanism in which the C–Si bond is formed through silyl radical addition to the heterocycle followed by subsequent β-hydrogen scission. DFT calculations reveal a reasonable energy profile for a radical mechanism and support the experimentally observed regioselectivity. The silylation reaction is shown to be reversible, with an equilibrium favoring products due to the generation of H_2 gas. In situ NMR experiments with deuterated substrates show that H_2 is formed by a cross-dehydrogenative mechanism. The stereochemical course at the silicon center was investigated utilizing a ^2H-labeled silolane probe; complete scrambling at the silicon center was observed, consistent with a number of possible radical intermediates or hypercoordinate silicates.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/75189, title ="Enantioselective Iridium-Catalyzed Allylic Alkylation Reactions of Masked Acyl Cyanide Equivalents", author = "Hethcox, J. Caleb and Shockley, Samantha E.", journal = "Organic Letters", volume = "19", number = "7", pages = "1527-1529", month = "April", year = "2017", doi = "10.1021/acs.orglett.7b00449", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170316-160746005", note = "© 2017 American Chemical Society. \n\nReceived 14 February 2017. Published online 14 March 2017. \n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for support of our research program. Additionally, J.C.H. thanks the Camille and Henry Dreyfus postdoctoral program in Environmental Chemistry, and S.E.S. thanks the NIH-NIGMS for a predoctoral fellowship (F31GM120804). Dr. Mona Shahgholi (Caltech) and Naseem Torian (Caltech) are thanked for mass spectrometry assistance. Dr. Scott Virgil (Caltech) is thanked for assistance with instrumentation. \n\nJ.C.H. and S.E.S. contributed equally. \n\nThe authors declare no competing financial interest.", revision_no = "22", abstract = "The first enantioselective iridium-catalyzed allylic alkylation reaction of a masked acyl cyanide (MAC) reagent has been developed. The transformation allows for the use of an umpoled synthon, which serves as a carbon monoxide equivalent. The reaction proceeds with good yield and excellent selectivity up to gram scale for a wide range of substituted allylic electrophiles, delivering products amenable to the synthesis of highly desirable, enantioenriched vinylated α-aryl carbonyl derivatives.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/77175, title ="Complex natural products as a driving force for discovery in organic chemistry", author = "Stoltz, Brian M.", pages = "ORGN-280", month = "April", year = "2017", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170503-152924409", note = "© 2017 American Chemical Society.", revision_no = "9", abstract = "Our lab. is deeply interested in the discovery and development of new reaction methodol. en route to the chem. synthesis of complex bioactive mols. Over the course of the past ten years, research in our group at the California Institute of Technol. has been initiated in the general area of synthetic chem., with a focus on the development of new strategies for the prepn. of complex mols., including natural products that possess interesting structural, biol., and phys. properties. Concurrent to this program of target driven synthesis is a strong effort directed toward the development of new techniques and reaction methods, which will be useful for a range of applications. Typically, the complex target structure is used as an inspiration for the discovery of new reactions and technologies that may eventually be regarded as general synthetic methodol. Consequently, this approach provides access to a) novel, medicinally relevant structures, b) a general method for their synthesis, and c) new synthetic methods that will be beneficial for a host of applications. Our group has been heavily involved in the synthesis of complex natural products such as the cyanthiwigins, quinocarcin, lemonomycin, and the dragmacidins. These naturally occurring mols. possess promising biol. properties ranging from activity against antibiotic-resistant bacteria, to antiproliferative, to anti-HIV action. Furthermore, they are structurally novel and are inherently a challenge to the state-of-the-art in synthetic\nchem. In the process of completing the synthesis of these important compds., we have developed a no. of new methods that enabled their access. These topics will be discussed in the lecture.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74219, title ="Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations", author = "Bhat, Vikram and Welin, Eric R.", journal = "Chemical Reviews", volume = "117", number = "5", pages = "4528-4561", month = "March", year = "2017", doi = "10.1021/acs.chemrev.6b00731", issn = "0009-2665", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170211-113501417", note = "© 2017 American Chemical Society. \n\nReceived: October 31, 2016;\nPublished: February 6, 2017.\n\nThis work was supported in part by the NIH-NIGMS (Grant R01GM080269), Caltech, the Gordon and Betty Moore Foundation, and the Margaret E. Early Medical Research Trust. E.R.W. was supported by a Postdoctoral Fellowship, PF-16-011-01-CDD, from the American Cancer Society. \n\nThe authors declare no competing financial interest.", revision_no = "22", abstract = "Stereoconvergent catalysis is an important subset of asymmetric synthesis that encompasses stereoablative transformations, dynamic kinetic resolutions, and dynamic kinetic asymmetric transformations. Initially, only enzymes were known to catalyze dynamic kinetic processes, but recently various synthetic catalysts have been developed. This Review summarizes major advances in nonenzymatic, transition-metal-promoted dynamic asymmetric transformations reported between 2005 and 2015.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74367, title ="Oxidative Fragmentations and Skeletal Rearrangements of Oxindole Derivatives", author = "Klare, Hendrik F. T. and Goldberg, Alexander F. G.", journal = "Organic Letters", volume = "19", number = "5", pages = "988-991", month = "March", year = "2017", doi = "10.1021/acs.orglett.6b03789", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170216-101807646", note = "© 2017 American Chemical Society. \n\nReceived: December 20, 2016; Published: February 14, 2017. \n\nThis work was supported by the NSF under the CCI Center for Selective C–H Functionalization (CHE-1205646). We thank DAAD (postdoctoral fellowship to H.F.T.K.), NSERC (graduate scholarship to A.F.G.G.), NSF (predoctoral research fellowship to D.C.D., No. DGE-1144469), the Gordon and Betty Moore Foundation, Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. Larry Henling (Caltech) is acknowledged for X-ray analysis, and Dr. Robert Craig and Dr. Guillaume Lapointe (both Caltech) are thanked for helpful discussions. \n\nThe authors declare no competing financial interest.", revision_no = "24", abstract = "An oxidative sequence for the conversion of oxindoles to structurally distinct heterocyclic scaffolds and aniline derivatives is disclosed by the combination of a copper-catalyzed C–H peroxidation and subsequent base-mediated fragmentation reaction. In contrast to classic enzymatic (i.e., kynurenine pathway) and biomimetic methods (i.e., Witkop–Winterfeldt oxidation) for oxidative indole cleavage, this protocol allows for the incorporation of external nucleophiles. The new transformation displays broad functional group tolerance and is applicable to tryptophan derivatives, opening potential new avenues for postsynthetic modification of polypeptides, bioconjugation, and unnatural amino acid synthesis.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/78814, title ="A Fischer Indolization Strategy toward the Total Synthesis of (–)-Goniomitine", author = "Pritchett, Beau P. and Kikuchi, Jun", journal = "Heterocycles", volume = "95", number = "2", pages = "1245-1253", month = "February", year = "2017", doi = "10.3987/COM-16-S(S)80 ", issn = "0385-5414", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170706-132827697", note = "© 2017 The Japan Institute of Heterocyclic Chemistry. \n\nPublished online: 15th February, 2017. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. B.P.P. thanks the NSF for a predoctoral fellowship (Grant DGE-1144469). Y. N. thanks Toray Industries Inc. for a postdoctoral fellowship. The authors thank Dr. Scott Virgil (Caltech) and the Caltech Center for Catalysis and Chemical Synthesis, for instrumentation assistance. Katerina Korch is acknowledged for experimental assistance.", revision_no = "22", abstract = "A Fischer indolization strategy toward the core of (–)-goniomitine is reported. Initial investigations into the Pd-catalyzed asymmetric allylic alkylation of dihydropyrido[1,2-a]indolone (DHPI) substrates are also discussed.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/73231, title ="Alkali metal hydroxide–catalyzed C(sp)–H bond silylation", author = "Toutov, Anton A. and Betz, Kerry N.", journal = "Journal of the American Chemical Society", volume = "139", number = "4", pages = "1668-1674", month = "February", year = "2017", doi = "10.1021/jacs.6b12114", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170104-153320118", note = "© 2016 American Chemical Society. \n\nReceived: November 23, 2016; Published: December 27, 2016. \n\nThis work was supported by the NSF under the CCI Center for Selective C–H Functionalization (CHE-1205646) and under CHE-\n1212767. A.A.T. is grateful to Bristol–Myers Squibb, the Resnick Sustainability Institute at Caltech, and to Dow Chemical for predoctoral fellowships as well as to NSERC for a PGS D fellowship. D.P.S thanks the CCI Center for Selective C–H Functionalization for support. W.-B.L thanks The Shanghai Institute of Organic Chemistry (SIOC) and S.-L. You for a postdoctoral fellowship. We thank S. Virgil and the Caltech Center for Catalysis and Chemical Synthesis for access to analytical equipment. M. Shahgoli and N. Torian (Caltech) are acknowledged for assistance with high-resolution mass spectrometry. \n\nA.A.T. and K.N.B. contributed equally. \n\nThe authors declare no competing financial interests.", revision_no = "28", abstract = "Disclosed is a mild, scalable, and chemoselective catalytic cross-dehydrogenative C–H bond functionalization protocol for the construction of C(sp)–Si bonds in a single step. The scope of the alkyne and hydrosilane partners is substantial, providing an entry point into various organosilane building blocks and additionally enabling the discovery of a number of novel synthetic strategies. Remarkably, the optimal catalysts are NaOH and KOH.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/70204, title ="Enantioselective, convergent synthesis of the ineleganolide core by a tandem annulation cascade", author = "Craig, Robert A., II and Roizen, Jennifer L.", journal = "Chemical Science", volume = "8", number = "1", pages = "507-514", month = "January", year = "2017", doi = "10.1039/c6sc03347d", issn = "2041-6520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160908-102036330", note = "© 2016 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. \n\nReceived 28 Jul 2016, Accepted 15 Aug 2016, First published online 17 Aug 2016. \n\nThe authors wish to thank the NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support and Eli Lilly & Co. for assistance with biological activity screening. Additionally, the authors gratefully acknowledge Larry Henling and Dr Michael Takase (Caltech) for X-ray crystallographic structural determination, Dr Mona Shahgholi and Naseem Torian (Caltech) for mass spectrometry assistance, and Dr David VanderVelde (Caltech) for NMR experimental assistance and helpful discussions. Additionally, Dr Jeffrey C. Holder, Dr Corey M. Reeves, Prof. Hosea M. Nelson, Dr Jonny R. Gordon, Dr Pamela M. Tadross, and Beau P. Pritchett (Caltech) and Dr Ryan Deluca and Dr Nick Cox (Stanford) are thanked for helpful discussions. R. A. C. gratefully acknowledges the support of this work provided by a fellowship from the National Cancer Institute of the National Institutes of Health (NIH) under Award Number F31A17435. J. L. R. thanks the California Tobacco-Related Disease Research Program of the University of California, Grant Number 14DT-0004 for a predoctoral fellowship. A. C. J. thanks the NIH for the support of this work provided by a postdoctoral fellowship (Award Number F32GM082000).", revision_no = "49", abstract = "An enantioselective and diastereoselective approach toward the synthesis of the polycyclic norditerpenoid ineleganolide is disclosed. A palladium-catalyzed enantioselective allylic alkylation is employed to stereoselectively construct the requisite chiral tertiary ether and facilitate the synthesis of a 1,3-cis-cyclopentenediol building block. Careful substrate design enabled the convergent assembly of the ineleganolide [6,7,5,5]-tetracyclic scaffold by a diastereoselective cyclopropanation–Cope rearrangement cascade under unusually mild conditions. Computational evaluation of ground state energies of late-stage synthetic intermediates was used to guide synthetic development and aid in the investigation of the conformational rigidity of these highly constrained and compact polycyclic structures. This work represents the first successful synthesis of the core structure of any member of the furanobutenolide-derived polycyclic norcembranoid diterpene family of natural products. Advanced synthetic manipulations generated a series of natural product-like compounds that were shown to possess selective secretory antagonism of either interleukin-5 or interleukin-17. This bioactivity stands in contrast to the known antileukemic activity of ineleganolide and suggests the norcembranoid natural product core may serve as a useful scaffold for the development of diverse therapeutics.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/72551, title ="Iridium-Catalyzed Stereoselective Allylic Alkylation Reactions with Crotyl Chloride", author = "Hethcox, J. Caleb and Shockley, Samantha E.", journal = "Angewandte Chemie International Edition", volume = "55", number = "52", pages = "16092-16095", month = "December", year = "2016", doi = "10.1002/anie.201609960", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20161205-102308894", note = "© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nManuscript received: October 11, 2016; Revised: October 27, 2016; First published: 28 November 2016. \n\nThe NIH-NIGMS (R01GM080269) and Caltech are thanked for support of our research program. Additionally, J.C.H. thanks the Camille and Henry Dreyfus postdoctoral program in Environmental Chemistry, and S.E.S. thanks the NIG-NIGMS for a predoctoral fellowship (F31GM120804). Dr. David VanderVelde is thanked for assistance with structural assignments via NMR analysis. Dr. Michael Takase, Dr. Lawrence Henling, and Niklas Thompson are acknowledged for X-ray analyses. Dr. Mona Shahgholi and Naseem Torian are thanked for mass spectrometry assistance. Dr. Scott Virgil is thanked for instrumentation assistance. Prof. Wen-bo Liu is thanked for helpful discussions.", revision_no = "26", abstract = "The development of the first enantio-, diastereo-, and regioselective iridium-catalyzed allylic alkylation reaction of prochiral enolates to form an all-carbon quaternary stereogenic center with an aliphatic-substituted allylic electrophile is disclosed. The reaction proceeds with good to excellent selectivity with a range of substituted tetralone-derived nucleophiles furnishing products bearing a newly formed vicinal tertiary and all-carbon quaternary stereodyad. The utility of this protocol is further demonstrated via a number of synthetically diverse product transformations.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/73187, title ="Single-step synthesis of 3-hydroxycarbazoles by annulation of electron-rich anilines and quinones", author = "Pushkarskaya, Eugenia and Wong, Brian", journal = "Tetrahedron Letters", volume = "57", number = "50", pages = "5653-5657", month = "December", year = "2016", doi = "10.1016/j.tetlet.2016.11.009", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170103-154034263", note = "© 2016 Elsevier. \n\nReceived 18 October 2016; accepted 2 November 2016; available online 4 November 2016. \n\nWe thank Dr. Francis Gosselin (Genentech, Inc.) for helpful discussion and reviewing the manuscript.", revision_no = "15", abstract = "A single-step synthesis of 3-hydroxycarbazoles has been achieved via annulation of electron-rich anilines and quinones in PhMe/AcOH (4:1) at room temperature. This chemistry tolerates various substituted benzoquinones and naphthoquinones, however, is sensitive to both the electronic and steric properties of the anilines. The desired 3-hydroxycarbazole derivatives are generally produced in moderate yield.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/71385, title ="A Second-Generation Synthesis of the Cyanthiwigin Natural Product Core", author = "Kim, Kelly E. and Stoltz, Brian M.", journal = "Organic Letters", volume = "18", number = "21", pages = "5720-5723", month = "November", year = "2016", doi = "10.1021/acs.orglett.6b02962", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20161024-113042085", note = "© 2016 American Chemical Society. \n\nReceived: September 30, 2016. Publication Date (Web): October 20, 2016. \n\nThis work was supported by the NSF under the CCI Center for Selective C–H Functionalization (CHE-1205646). Additional financial support was provided by Caltech and Novartis. Dr. Scott C. Virgil (Caltech), Dr. John A. Enquist, Jr. (Gilead), and Dr. Grant M. Shibuya (SiteOne Therapeutics) are acknowledged for helpful discussions. \n\nThe authors declare no competing financial interest.", revision_no = "25", abstract = "An improved synthesis of the cyanthiwigin natural product core enabled by new catalytic technology is reported. The key double catalytic enantioselective alkylation has been reoptimized using a recently developed protocol employing low loadings of palladium catalyst, thereby facilitating large-scale production of the tricyclic cyanthiwigin framework. Additionally, preparation of the penultimate aldehyde intermediate is expedited through the application of anti-Markovnikov Tsuji–Wacker oxidation.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/71377, title ="Palladium-Catalyzed Aerobic Intramolecular Aminoacetoxylation of Alkenes Enabled by Catalytic Nitrate", author = "Li, Jiaming and Grubbs, Robert H.", journal = "Organic Letters", volume = "18", number = "21", pages = "5449-5451", month = "November", year = "2016", doi = "10.1021/acs.orglett.6b02722", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20161024-103416597", note = "© 2016 American Chemical Society. \n\nReceived: September 9, 2016; Publication Date (Web): October 18, 2016. \n\nThe authors thank the NIH (R01GM031332 and R01GM080269) and Caltech for financial support. Dr. Scott C. Virgil (Caltech) is thanked for assistance with GC analysis. Dr. David VanderVelde (Caltech) and Dr. Mona Shahgholi (Caltech) are acknowledged for help in structural determination and characterizations. \n\nThe authors declare no competing financial interest.", revision_no = "28", abstract = "A mild aerobic intramolecular aminoacetoxylation method for the synthesis of pyrrolidine and indoline derivatives was achieved using molecular oxygen as the oxidant. A catalytic NO_x species acts as an electron transfer mediator to access a high-valent palladium intermediate as the presumed active oxidant.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/70603, title ="Enantioselective Pd-Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2-a]indolone Substrates: Efficient Syntheses of (−)-Goniomitine, (+)-Aspidospermidine, and (−)-Quebrachamine", author = "Pritchett, Beau P. and Kikuchi, Jun", journal = "Angewandte Chemie International Edition", volume = "55", number = "43", pages = "13529-13532", month = "October", year = "2016", doi = "10.1002/anie.201608138", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160927-100108036", note = "© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nReceived: August 19, 2016; Revised: September 7, 2016; First published: 26 September 2016. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. B.P.P. thanks the NSF for a predoctoral fellowship (Grant DGE-1144469). Y.N. thanks Toray Industries Inc. for a postdoctoral fellowship. The authors thank Mona Shahgholi and Naseem Torian for mass spectrometry assistance, and Dr. Scott Virgil (Caltech) and the Caltech Center for Catalysis and Chemical Synthesis, for instrumentation assistance.", revision_no = "28", abstract = "The successful application of dihydropyrido[1,2-a]indolone (DHPI) substrates in Pd-catalyzed asymmetric allylic alkylation chemistry facilitates rapid access to multiple alkaloid frameworks in an enantioselective fashion. Strategic bromination at the indole C3 position greatly improved the allylic alkylation chemistry and enabled a highly efficient Negishi cross-coupling downstream. The first catalytic enantioselective total synthesis of (−)-goniomitine, along with divergent formal syntheses of (+)-aspidospermidine and (−)-quebrachamine, are reported herein.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/70776, title ="Catalytic Anti-Markovnikov Transformations of Hindered Terminal Alkenes Enabled by Aldehyde-Selective Wacker-Type Oxidation", author = "Kim, Kelly E. and Li, Jiaming", journal = "Journal of the American Chemical Society", volume = "138", number = "40", pages = "13179-13182", month = "October", year = "2016", doi = "10.1021/jacs.6b08788", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20161003-161852128", note = "© 2016 American Chemical Society. \n\nReceived: August 25, 2016. Publication Date (Web): September 27, 2016. \n\nThis manuscript is dedicated to Professor Samuel J. Danishefsky on the occasion of his 80th birthday. This work was supported by the NSF under the CCI Center for Selective C–H Functionalization, CHE-1205646. Additional financial support was provided by Caltech and Novartis. Dr. Mona Shahgholi and Naseem Torian are acknowledged for assistance with high-resolution mass spectrometry. Dr. Yiyang Liu, Nicholas R. O’Connor, Dr. Allen Y. Hong, and Prof. Wen-Bo Liu are acknowledged for contributions to substrate preparation. Beau P. Pritchett is thanked for preparation of the Ohira–Bestmann reagent. \n\nThe authors declare no competing financial interest.", revision_no = "26", abstract = "A new strategy for the functionalization of sterically hindered terminal olefins is reported. Alkenes bearing quaternary carbons at the allylic or homoallylic position are readily oxidized to the corresponding aldehydes by palladium/copper/nitrite catalysis. A broad range of functional groups including esters, nitriles, silyl ethers, vinylogous esters, ketones, lactones, and β-ketoesters are tolerated under the reaction conditions. The crude aldehyde products can be transformed further, enabling direct conversion of hindered terminal alkenes to various other synthetically useful functional groups, resulting in formal anti-Markovnikov hydroamination, among other transformations.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/73319, title ="Escherichia coli K1 Modulates Peroxisome Proliferator–Activated Receptor γ and Glucose Transporter 1 at the Blood-Brain Barrier in Neonatal Meningitis", author = "Krishnan, Subramanian and Chang, Alexander C.", journal = "Journal of Infectious Diseases", volume = "214", number = "7", pages = "1092-1104", month = "October", year = "2016", doi = "10.1093/infdis/jiw306", issn = "0022-1899", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170106-160004918", note = "© 2016 The Author. Published by Oxford University Press for the Infectious Diseases Society of America. \n\nReceived May 20, 2015; Accepted July 13, 2016; First published online: July 24, 2016. \n\nWe thank G. Esteban Fernandez for assistance with confocal imaging. \n\nThis work was supported by the National Institute of Allergy and Infectious Diseases (AI40567) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NS73115 to N. V. P.). \n\nPotential conflicts of interest: All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.", revision_no = "24", abstract = "Escherichia coli K1 meningitis continues to be a major threat to neonatal health. Previous studies demonstrated that outer membrane protein A (OmpA) of E. coli K1 interacts with endothelial cell glycoprotein 96 (Ecgp96) in the blood-brain barrier to enter the central nervous system. Here we show that the interaction between OmpA and Ecgp96 downregulates peroxisome proliferator–activated receptor γ (PPAR-γ) and glucose transporter 1 (GLUT-1) levels in human brain microvascular endothelial cells, causing disruption of barrier integrity and inhibition of glucose uptake. The suppression of PPAR-γ and GLUT-1 by the bacteria in the brain microvessels of newborn mice causes extensive pathophysiology owing to interleukin 6 production. Pretreatment with partial or selective PPAR-γ agonists ameliorate the pathological outcomes of infection by suppressing interleukin 6 production in the brain. Thus, inhibition of PPAR-γ and GLUT-1 by E. coli K1 is a novel pathogenic mechanism in meningitis, and pharmacological upregulation of PPAR-γ and GLUT-1 levels may provide novel therapeutic avenues. ", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/70928, title ="Enantioconvergent catalysis", author = "Mohr, Justin T. and Moore, Jared T.", journal = "Beilstein Journal of Organic Chemistry", volume = "12", pages = "2038-2045", month = "September", year = "2016", doi = "10.3762/bjoc.12.192", issn = "1860-5397", url = "https://resolver.caltech.edu/CaltechAUTHORS:20161006-142747894", note = "© 2016 Mohr et al.; licensee Beilstein-Institut. This is an Open Access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (http://www.beilstein-journals.org/bjoc) \n\nReceived: 29 July 2016. Accepted: 25 August 2016. Published: 16 September 2016. \n\nThis article is part of the Thematic Series \"Strategies in asymmetric catalysis\". Guest Editor: T. P. Yoon. \n\nThis publication is supported in part by the NIH-NIGMS (R01GM080269), Amgen, Eli Lilly (predoctoral fellowship to J. Mohr), and NIH 1F32 (GM116304-01) (postdoctoral fellowship to J. Moore). Additionally, we thank David C. Ebner for helpful discussions.", revision_no = "10", abstract = "An enantioconvergent catalytic process has the potential to convert a racemic starting material to a single highly enantioenriched product with a maximum yield of 100%. Three mechanistically distinct approaches to effecting enantioconvergent catalysis are identified, and recent examples of each are highlighted. These processes are compared to related, non-enantioconvergent methods.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/69814, title ="Iridium-Catalyzed Diastereo-, Enantio-, and Regioselective Allylic Alkylation with Prochiral Enolates", author = "Hethcox, J. Caleb and Shockley, Samantha E.", journal = "ACS Catalysis", volume = "6", number = "9", pages = "6207-6213", month = "September", year = "2016", doi = "10.1021/acscatal.6b01886", issn = "2155-5435", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160822-135959905", note = "© 2016 American Chemical Society. \n\nReceived: July 6, 2016; Publication Date (Web): August 17, 2016. \n\nThe authors thank the many past and present co-workers whose efforts have made our contributions in iridium-catalyzed allylic alkylation possible: Prof. Wen-Bo Liu, Dr. Corey M. Reeves, Dr. Scott C. Virgil, Dr. Noriko Okamoto, Eric J. Alexy, Dr. Allen Y. Hong, and Dr. Kristy Tran. Support for our program has been made available from the NIH-NIGMS (R01GM080269) and Caltech. Additionally, J.C.H. thanks the Camille and Henry Dreyfus postdoctoral program in Environmental Chemistry, and S.E.S. thanks the NIH-NIGMS for a predoctoral fellowship (F31GM120804). \n\nThe authors declare no competing financial interest.", revision_no = "31", abstract = "Transition-metal-catalyzed asymmetric allylic alkylation of\nenolates is a powerful method for the formation of carbon−\ncarbon bonds. Within this field, palladium-catalyzed allylic\nalkylation reactions have undoubtedly been the most studied.\nAside from limited cases, palladium catalysts preferentially\nform the linear substitution product through alkylation at the\nless-substituted terminus of the allylic electrophile (Scheme 1).\nHowever, in contrast to palladium, most other transition metals\n(e.g., Mo, W, Fe, Ru, Co, Rh, Ni, Pt, and Ir) have been shown\nto favor the construction of the branched product, with iridium\ncatalysts being some of the most efficient and selective. The\npotential application of these chiral, branched products to the\nsynthesis of natural products and biologically active compounds\nhas motivated the development of practical and reliable\ntransition-metal-catalyzed methods for their construction.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/70413, title ="Potassium tert-Butoxide-Catalyzed Dehydrogenative Cross-Coupling of Heteroarenes with Hydrosilanes", author = "Toutov, Anton A. and Liu, Wen-Bo", journal = "Organic Syntheses", volume = "93", pages = "263-271", month = "August", year = "2016", doi = "10.15227/orgsyn.093.0263", issn = "0078-6209", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160919-073857486", note = "© 2016 Organic Syntheses, Inc. \n\nPublished on the web 08/26/2016. \n\nThis publication is based on work supported by the NSF under the CCI Center for Selective C-H Functionalization (CHE-1205646) and under CHE-1212767. W.-B.L. wishes to thank the Shanghai Institute of Organic Chemistry (SIOC) and Prof. S.-L. You for a postdoctoral fellowship. A.A.T. is grateful to the Resnick Sustainability Institute at Caltech and to Dow Chemical for a predoctoral fellowship, and to NSERC for a PGS D fellowship. We also thank Dr. Scott Virgil and the Caltech Center for Catalysis and Chemical Synthesis for access to analytical equipment. \n\nA.A.T. and W.-B.L. contributed equally to this work.", revision_no = "21", abstract = "A. 1-Methyl-2-(triethylsilyl)-1H-indole (2). An oven-dried 100-mL round-bottom Schlenk flask is equipped with a Teflon-coated magnetic stir bar (25 x 8 mm) and capped with a rubber septum (Note 1). The side arm of the flask is connected to Schlenk line and the flask is cooled to room temperature under vacuum and back-filled with nitrogen. Potassium tert-butoxide (1.34 g, 12.0 mmol, 0.2 equiv) is added to the flask under positive nitrogen flow (Notes 2 and 3), and then the flask is evacuated and back-filled with nitrogen three times. N-Methylindole (7.48 mL, 7.86 g, 60.0 mmol, 1.0 equiv) and triethylsilane (28.6 mL, 20.82 g, 179.5 mmol, 3.0 equiv) are added sequentially via syringe through the septum, resulting in a yellow heterogeneous mixture (Figure 1). After the septum is replaced with a glass stopper (Note 4), the reaction mixture is degassed (Note 5) and stirred at 45 ºC for 76 h (Note 6), resulting in a dark purple solution. The heating bath is removed and the reaction mixture is allowed to cool to ambient temperature (~25 ºC), then anhydrous diethyl ether (30 mL) is added slowly while stirring (Note 7).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/69191, title ="Ni-Catalyzed Enantioselective C-Acylation of α-Substituted Lactams", author = "Hayashi, Masaki and Bachman, Shoshana", journal = "Journal of the American Chemical Society", volume = "138", number = "29", pages = "8997-9000", month = "July", year = "2016", doi = "10.1021/jacs.6b02120", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160725-104304872", note = "© 2016 American Chemical Society. \n\nReceived: February 25, 2016. Received: February 25, 2016. \n\nThe authors thank NIH-NIGMS (R01GM080269), Daiichi-Sankyo Co., Ltd. (M.H.), JSPS (S.H.), MEXT (S.H.), the Caltech 3CS, and Caltech for financial support. C.C.E. also thanks Loyola University Chicago for financial support. Mr. Hashiru Negishi (Caltech), Mr. Larry Henling (Caltech), and Dr. Scott Virgil (Caltech) are acknowledged for helpful discussions, instrumentation, and experimental assistance. \n\nThe authors declare no competing financial interest.", revision_no = "34", abstract = "A new strategy for catalytic enantioselective C-acylation to generate α-quaternary-substituted lactams is reported. Ni-catalyzed three-component coupling of lactam enolates, benzonitriles, and aryl halides produces β-imino lactams that then afford β-keto lactams by acid hydrolysis. Use of a readily available Mandyphos-type ligand and addition of LiBr enable the construction of quaternary stereocenters on α-substituted lactams to form β-keto lactams in up to 94% ee.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/70414, title ="Preparation of 1,5-Dioxaspiro[5.5]undecan-3-one", author = "Craig, Robert A., II and Smith, Russell C.", journal = "Organic Syntheses", volume = "93", pages = "210-227", month = "July", year = "2016", doi = "10.15227/orgsyn.093.0210", issn = "2333-3553", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160919-074608608", note = "© 2016 Organic Syntheses, Inc. \n\nPublished on the Web 07/21/2016.", revision_no = "11", abstract = "A. 3-Amino-3-(hydroxymethyl)-1,5-dioxaspiro[5.5]undecane. A 1-L single-necked, round-bottomed flask is equipped with an egg-shaped, Teflon®-coated magnetic stirring bar (3.5 cm x 1.5 cm), capped with a rubber septum, flame-dried under vacuum, and cooled under an argon atmosphere (Note 1). After cooling to ambient temperature (21-23 °C), to the flask is added anhydrous N,N-dimethylformamide (DMF, 365 mL, 0.78 M) via cannula. Subsequently, tris(hydroxymethyl)aminomethane hydrochloride (45.0 g, 286 mmol, 1.00 equiv) (Note 2 and 3) is added in a single portion as white crystalline solid. The reaction vessel is immediately resealed with a rubber septum under inert atmosphere and stirring is commenced (Figure 1). To this white suspension is added 1,1-dimethoxycyclohexane (50.0 mL, 47.4 g, 329 mmol, 1.15 equiv) via syringe in one portion (Note 4). Lastly, to the off-white slurry is added para-toluenesulfonic acid monohydrate (p-TsOH•H2O, 1.63 g, 8.57 mmol, 0.03 equiv) as a solid in one portion quickly, immediately replacing the rubber septum to maintain an inert atmosphere.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/68874, title ="Catalytic enantioselective total synthesis of (+)-eucomic acid", author = "Estipona, Benzi I. and Pritchett, Beau P.", journal = "Tetrahedron", volume = "72", number = "26", pages = "3707-3712", month = "June", year = "2016", doi = "10.1016/j.tet.2016.02.059", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160707-080125930", note = "© 2016 Elsevier Ltd.\n\nReceived 21 January 2016; Received in revised form 24 February 2016; Accepted 25 February 2016; Available online 2 March 2016.\n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen,\nthe Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support.\nB.I.E. thanks the Caltech Summer Undergraduate Research Fellowship (SURF) program for summer research funding. B.P.P. thanks the NSF for a predoctoral fellowship. R.A.C. gratefully acknowledges the support of this work provided by a predoctoral fellowship from the National Cancer Institute of the National Institutes of Health under Award No. F31A17435. The authors thank Dr. Mona Shahgholi and Naseem Torian for mass spectrometry assistance and Dr. Scott C. Virgil (Caltech) for instrumentation assistance.", revision_no = "19", abstract = "A catalytic enantioselective synthesis of (+)-eucomic acid is reported. A palladium-catalyzed asymmetric allylic alkylation is employed to access the chiral tetrasubstituted α-hydroxyacid moiety found in the natural product. The protecting group strategy was investigated, and a protecting group manipulation was made without any appreciable deleterious effects in the allylic alkylation reaction. Non-natural (+)-eucomic acid is synthesized in a longest linear sequence of 13 steps.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/68881, title ="Tetrahedron Young Investigator Award ~ 2016", author = "Stoltz, Brian M. and Martin, Stephen", journal = "Tetrahedron", volume = "72", number = "26", pages = "iii", month = "June", year = "2016", doi = "10.1016/j.tet.2016.04.026", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160707-090355308", note = "© 2016 Elsevier Ltd. \n\nAvailable online 11 April 2016.", revision_no = "11", abstract = "The Executive Board of Directors for Tetrahedron Publications is pleased to recognize the outstanding achievements of Professor Neil K. Garg of the University of California, Los Angeles (UCLA) and has awarded him a Tetrahedron Young Investigator Award in recognition of his exceptional creativity and contributions to the field of organic synthesis, especially for the development and application of novel methods and strategies for the synthesis of complex natural products. Professor Garg will present his award address at the Tetrahedron Symposium held in Sitges, Spain in June 2016. To honor and commemorate his receipt of this award, this special Symposium-in-Print entitled, New Reactions and Methods and Their Applications to Complex Molecule Synthesis has been organized. We are grateful to the contributors to this issue for their outstanding accomplishments that have led to the production of this unique issue and congratulate Professor Garg on this honor.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/67803, title ="Synthesis of Aryl Ketoamides via Aryne Insertion into Imides", author = "Wright, Austin C. and Haley, Christopher K.", journal = "Organic Letters", volume = "18", number = "12", pages = "2793-2795", month = "June", year = "2016", doi = "10.1021/acs.orglett.6b00994", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160609-145221780", note = "© 2016 American Chemical Society. \n\nPublication Date (Web): June 7, 2016. \n\nThe authors thank the NSF (CCE 1265591), Caltech, and Amgen for financial support. G.L. is grateful to the Swiss National Science Foundation (SNSF) for a postdoctoral fellowship. Dr. Scott C. Virgil (Caltech) is thanked for assistance with compound isolation. Dr. Mona Shahgholi (Caltech) is acknowledged for help in structural determination and characterizations. \n\nThe authors declare no competing financial interest.", revision_no = "21", abstract = "An insertion of arenes into both imides and anhydrides via reactive aryne intermediates is presented. The reaction is performed under exceptionally mild conditions, and the corresponding ketoamide products are amenable to derivatization to deliver a variety of synthetically useful motifs such as quinolones, indoles, and ketoanilines.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/66937, title ="Nickel-Catalyzed Intramolecular C−O Bond Formation: Synthesis of Cyclic Enol Ethers", author = "Han, Seo-Jung and Doi, Ryohei", journal = "Angewandte Chemie International Edition", volume = "55", number = "26", pages = "7437-7440", month = "June", year = "2016", doi = "10.1002/anie.201601991", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160510-141655234", note = "© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nManuscript received 25 February 2016; version of record online 9 May 2016; issue online 15 June 2016. \n\nWe wish to thank the NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support. S.-J.H. thanks the Fulbright program (Foreign Student Program, No. 15111120) and the Ilju Foundation of Education & Culture (Pre-doctoral Research Fellowship) for financial support. R.D. is grateful for support as a JSPS research fellow. Dr. Mona Shahgholi (Caltech) and Naseem Torian (Caltech) are acknowledged for high-resolution mass spectrometry assistance. Dr. Scott\u2005C. Virgil (Caltech) is thanked for helpful discussions.", revision_no = "32", abstract = "An efficient and exceptionally mild intramolecular nickel-catalyzed carbon–oxygen bond-forming reaction between vinyl halides and primary, secondary, and tertiary alcohols has been achieved. Zinc powder was found to be an essential additive for obtaining high catalyst turnover and yields. This operationally simple method allows direct access to cyclic vinyl ethers in high yields in a single step.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/64153, title ="Synthetic Applications and Methodological Developments of Donor-Acceptor Cyclopropanes and Related Compounds", author = "O'Connor, Nicholas R. and Wood, John L.", journal = "Israel Journal of Chemistry", volume = "56", number = "6-7", pages = "431-444", month = "June", year = "2016", doi = "10.1002/ijch.201500089", issn = "0021-2148", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160202-091959130", note = "© 2016 Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim. \n\nReceived: November 9, 2015; Accepted: December 7, 2015; Article first published online: 27 Jan. 2016. \n\nThe authors thank the coworkers whose efforts have made our contributions to the chemistry of donor-acceptor cyclopropanes and related compounds possible: Jennifer M. Chen, Robert A. Craig, II, Hans-Jürgen Dietrich, Julie A. Dixon, Brian D. Doan, John A. Enquist, Jr., Eric M. Ferreira, Alexander F. G. Goldberg, Timothy P. Heffron, Alexandra A. Holubec, Michael E. Meyer, Dejah T. Petsch, Derek A. Pflum, John H. Phillips, Richmond Sarpong, Mohammed F. Shamji, Grant M. Shibuya, Julius T. Su, Uttam K. Tambar, and Matthew M. Weiss. Financial support from the A. P. Sloan Foundation, Abbott, the American Cancer Society (JFRA-523), Amgen, Astellas Pharma, AstraZeneca, Bayer Corporation, Boehringer Ingelheim, Bristol-Myers Squibb, Caltech, the Camille and Henry Dreyfus Foundation, Eli Lilly, the Elsa U. Pardee Foundation, GlaxoSmithKline, Johnson & Johnson, Merck, the NIH-NIGMS (R01GM080269), Novartis, the NSF CCI Center for Selective C-H Functionalization (CHE-1205646), Pfizer, the Research Corporation, Roche, and Yale University is gratefully acknowledged. J.L.W. is grateful for generous funding from Baylor University, the Welch Foundation (Chair, AA-006), and the Cancer Prevention & Research Institute of Texas (CPRIT, R1309).", revision_no = "33", abstract = "Donor-acceptor cyclopropanes are convenient precursors to reactive and versatile 1,3-dipoles, and have found application in the synthesis of a variety of carbo- and heterocyclic scaffolds. This perspective review details our laboratory’s use of donor-acceptor cyclopropanes as intermediates toward the total synthesis of various natural products. We also discuss our work in the development of novel cycloadditions and rearrangements of donor-acceptor cyclopropanes and aziridines, as well as an example of an aryne insertion proceeding via fragmentation of a transient donor-acceptor cyclobutane.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/66575, title ="A mild and efficient approach to enantioenriched α-hydroxyethyl α,β-unsaturated δ-lactams", author = "Han, Seo-Jung and Stoltz, Brian M.", journal = "Tetrahedron Letters", volume = "57", number = "21", pages = "2233-2235", month = "May", year = "2016", doi = "10.1016/j.tetlet.2016.04.022", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160502-084148448", note = "© 2016 Elsevier Ltd. \n\nReceived 15 March 2016; Revised 5 April 2016; Accepted 7 April 2016; Available online 9 April 2016. \n\nThe authors wish to thank the NIH-NIGMS (R01GM080269-01), Amgen, and Caltech for financial support. S.-J.H thanks Fulbright (Foreign Student Program, No. 15111120) and the Ilju Foundation of Education & Culture (Pre-doctoral Research Fellowship) for financial support. Dr. Mona Shahgholi (Caltech) and Naseem Torian (Caltech) are acknowledged for high-resolution mass spectrometry assistance.", revision_no = "17", abstract = "A straightforward approach toward enantioenriched α-substituted α,β-unsaturated δ-lactams is described. Although a considerable number of approaches toward α,β-unsaturated δ-lactams have been reported, there are relatively few examples of enantioenriched α,δ-disubstituted α,β-unsaturated δ-lactams formation. The δ-stereocenter was formed by addition of allylmagnesium bromide to an N-tert-butylsulfinyl imine. The α,β-unsaturated δ-lactam was furnished by ring-closing metathesis. Although Baylis–Hillman chemistry failed on this cyclic compound, introduction of the hydroxyethyl group prior to ring-closing metathesis was successful. A Baylis–Hillman reaction was used to introduce the substituent at the α-position of the α,β-unsaturated lactam.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/66506, title ="Enantioselective γ-Alkylation of α,β-Unsaturated Malonates and Ketoesters by a Sequential Ir-Catalyzed Asymmetric Allylic Alkylation/Cope Rearrangement", author = "Liu, Wen-Bo and Okamoto, Noriko", journal = "Journal of the American Chemical Society", volume = "138", number = "16", pages = "5234-5237", month = "April", year = "2016", doi = "10.1021/jacs.6b02153", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160427-092037065", note = "© 2016 American Chemical Society. Received: February 26, 2016. Published: April 7, 2016.\n\nWe thank NIH-NIGMS (R01GM080269), the Gordon and Betty Moore Foundation, and Caltech for financial support. Shanghai Institute of Organic Chemistry (SIOC) is thanked for a postdoctoral fellowship to W.-B.L. Hiroshima International University is thanked for a postdoctoral fellowship to N.O. E.J.A. is grateful to the National Science Foundation for a predoctoral fellowship. K.T. acknowledges support from California HIV/AIDS Research Program (F08-CT-201). Mr. Lawrence Henlingand Dr. Michael Takase are acknowledged for X-ray analyses. We thank Dr. David VanderVelde for NMR expertise, and Dr. Mona Shahgholi and Naseem Torian for mass spectrometry assistance. The authors are also thankful to Professor Shu-Li You for the\ngenerous donation of N-aryl ligands and for helpful discussions.", revision_no = "28", abstract = "A catalytic, enantioselective γ-alkylation of α,β-unsaturated malonates and ketoesters is reported. This strategy entails a highly regio- and enantioselective iridium-catalyzed α-alkylation of an extended enolate, and a subsequent translocation of chirality to the γ-position via a Cope rearrangement.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/66457, title ="Enantioselective Synthesis of Caprolactam and Enone Precursors to the Heterocyclic DEFG Ring System of Zoanthenol", author = "Bagdanoff, Jeffrey T. and Behenna, Douglas C.", journal = "European Journal of Organic Chemistry", volume = "2016", number = "12", pages = "2101-2104", month = "April", year = "2016", doi = "10.1002/ejoc.201600223", issn = "1434-193X", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160425-132914132", note = "© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nReceived: February 26, 2016; Article first published online: 19 APR 2016. \n\nThe authors wish to thank the NIH-NIGMS (R01GM080269), the Tobacco Related Disease Research Program (Fellowship to J. T. B.), the John and Fannie Hertz Foundation (predoctoral fellowship to D. C. B.), Novartis (predoctoral fellowship to J. L. S.), the Philanthropic Education Organization (Scholar Award to J. L. S.), and Abbott, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, and Caltech for their generous financial support. The authors thank Professor Karl Scheidt (Northwestern) for helpful early discussions.", revision_no = "28", abstract = "The enantioselective synthesis of both caprolactam and enone synthons for the DEFG ring system of zoanthenol are described. The evolution of this approach proceeds first through a synthesis using the chiral pool as a starting point. Challenges in protecting-group strategy led to the modification of this approach beginning with (±)-glycidol. Ultimately, an efficient approach was developed by employing an asymmetric hetero-Diels–Alder reaction. The caprolactam building block can be converted by an interesting selective Grignard addition into the corresponding enone synthon. Addition of a model alkyne provides support for the late-stage addition of a hindered alkyne to the caprolactam building block.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/64138, title ="Development of a simple system for the oxidation of electron-rich diazo compounds to ketones", author = "O’Connor, Nicholas R. and Bolgar, Peter", journal = "Tetrahedron Letters", volume = "57", number = "8", pages = "849-851", month = "February", year = "2016", doi = "10.1016/j.tetlet.2016.01.020", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160201-141332316", note = "© 2016 Elsevier Ltd. \n\nReceived 7 December 2015, Revised 5 January 2016, Accepted 6 January 2016, Available online 8 January 2016. \n\nThe authors wish to thank the NSF (CHE-1265591), Amgen, and Caltech for financial support. P.B. is grateful to St Catharine’s College (University of Cambridge) and the Haller US Travel Fund for their support of an undergraduate summer research exchange program. Dr. David VanderVelde (NMR), Dr. Mona Shahgholi (HRMS), and Shoshana Bachman (ATR-IR) are thanked for assistance with characterization.", revision_no = "14", abstract = "Mild heating of diazo compounds in DMSO furnishes ketone products in moderate to excellent yields. The\nreaction is particularly effective on electron-rich substrates and exhibits high chemoselectivity, allowing\nfor the use of diazo compounds containing additional oxidation-prone functional groups. This straightforward\nprotocol offers an alternate route to synthetically useful ɑ-ketoesters from readily available aryl diazoacetates.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/63562, title ="Production and Fate of C_4 Dihydroxycarbonyl Compounds from Isoprene Oxidation", author = "Bates, Kelvin H. and Nguyen, Tran B.", journal = "Journal of Physical Chemistry A", volume = "120", number = "1", pages = "106-117", month = "January", year = "2016", doi = "10.1021/acs.jpca.5b10335", issn = "1089-5639", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160112-074404722", note = "© 2015 American Chemical Society. \n\nReceived: October 21, 2015. Revised: December 13, 2015. Publication Date (Web): December 15, 2015. \n\nThis material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant DGE-1144469. Additionally, the authors thank the NSF (AGS-1240604) and the Electric Power Research Institute for supporting this work. Development of the GC-ToF-CIMS is supported by an award from the NSF’s Major Research Instrumentation Program (AGS-1428482). \n\nThe authors declare no competing financial interest.", revision_no = "25", abstract = "Isoprene epoxydiols (IEPOX) are formed in high yield as second-generation products of atmospheric isoprene oxidation in pristine (low-NO) environments. IEPOX has received significant attention for its ability to form secondary organic aerosol, but the fate of IEPOX in the gas phase, and those of its oxidation products, remains largely unexplored. In this study, three dihydroxycarbonyl compounds with molecular formula of C_4H_8O_3, putative products of IEPOX oxidation, are synthesized to determine their isomer-specific yields from IEPOX. We find that 3,4-dihydroxy-2-butanone (DHBO) comprises 43% and 36% of the products from cis- and trans-β-IEPOX, respectively, and is by far the most abundant C_4H_8O_3 dihydroxycarbonyl compound produced by this mechanism. OH is found to react with DHBO with a rate coefficient of 1.10 × 10^(–11) cm^3 molecule^(–1) s^(–1) at 297 K, forming two hydroxydicarbonyl compounds that share the molecular formula C_4H_6O_3 with unitary yield. The results of this study are compared with field observations and used to propose a multigenerational mechanism of IEPOX oxidation. Finally, global simulations using GEOS-Chem, a chemical transport model, show that the C_4H_8O_3 dihydroxycarbonyl compounds and their oxidation products are widespread in the atmosphere and estimate annual global production of C_4H_8O_3 dihydroxycarbonyls to be 54 Tg\u202fy^(–1), primarily as DHBO.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/63538, title ="Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators", author = "Su, Judith and Goldberg, Alexander F. G.", journal = "Light: Science and Applications", volume = "5", number = "1", pages = "Art. No. e16001", month = "January", year = "2016", doi = "10.1038/lsa.2016.1", issn = "2047-7538", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160111-102110097", note = "© 2016 CIOMP. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/. \n\nReceived: 6 March 2015; revised: 24 July 2015; accepted: 5 August 2015; accepted article preview online 22 August 2015. Published online 1 January 2016. \n\nWe thank Raymond Deshaies for the ribosomes, Carver Mead for the frequency locking suggestion, Richard Murray for discussions on feedback control, Andrew Raubitschek for the exosomes, Stephen Holler and Mark Oxborrow for COMSOL assistance, and Scott Fraser, Rob Phillips, and Kerry Vahala for comments and discussion of the manuscript.", revision_no = "14", abstract = "Single-molecule detection is one of the fundamental challenges of modern biology. Such experiments often use labels that can be expensive, difficult to produce, and for small analytes, might perturb the molecular events being studied. Analyte size plays an important role in determining detectability. Here we use laser-frequency locking in the context of sensing to improve the signal-to-noise ratio of microtoroid optical resonators to the extent that single nanoparticles 2.5 nm in radius, and 15.5 kDa molecules are detected in aqueous solution, thereby bringing these detectors to the size limits needed for detecting the key macromolecules of the cell. Our results, covering several orders of magnitude of particle radius (100 nm to 2 nm), agree with the ‘reactive’ model prediction for the frequency shift of the resonator upon particle binding. This confirms that the main contribution of the frequency shift for the resonator upon particle binding is an increase in the effective path length due to part of the evanescent field coupling into the adsorbed particle. We anticipate that our results will enable many applications, including more sensitive medical diagnostics and fundamental studies of single receptor–ligand and protein–protein interactions in real time.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/81560, title ="Asymmetric Synthesis of Quaternary Stereocenters via Metal Enolates", author = "Korch, Katerina M. and Loskot, Steven A.", pages = "1-85", month = "January", year = "2016", doi = "10.1002/9780470682531.pat0858", isbn = "9780470682531", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170919-091408635", note = "© 2016 John Wiley & Sons, Ltd. \n\nPublished Online: 15 SEP 2017.", revision_no = "10", abstract = "The strategy of using chiral metal enolate intermediates in a diverse variety of asymmetric transformations has allowed the generation of quaternary stereocenter-bearing products that are otherwise difficult to access. Many classic transformations including aldol, Mannich, conjugate addition, alkylation, and pericyclic-type reactions, as well as allylic alkylation and α-arylation/alkenylation, have been adapted to proceed through chiral metal enolate intermediates, allowing the asymmetric synthesis of many complex products in both an intermolecular and intramolecular manner. These transformations have proven useful in the synthesis of natural products and may also be applied to the synthesis of novel pharmaceuticals and other compounds of interest in the future. This review includes work done up to and including the year 2014.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/63769, title ="Total Synthesis and Characterization of 7-Hypoquinuclidonium Tetrafluoroborate and 7-Hypoquinuclidone BF_3 Complex", author = "Liniger, Marc and VanderVelde, David G.", journal = "Journal of the American Chemical Society", volume = "138", number = "3", pages = "969-974", month = "December", year = "2015", doi = "10.1021/jacs.5b11750", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20160119-141029568", note = "© 2015 American Chemical Society. \n\nReceived: November 9, 2015. Publication Date (Web): December 29, 2015. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support. M.L. thanks the Swiss National Science Foundation (SNSF) for a postdoctoral fellowship (P2EZP2_148751). Jonathan Rittle is acknowledged for assistance with the ATR-IR and the Peters group for using their equipment. We are indebted to Dr. Kousouke Tani and Dr. Michael Krout for taking the first steps in creating the twisted amide project and for establishing their synthesis, isolation and crystallization. \n\nThe authors declare no competing financial interest.", revision_no = "41", abstract = "Derivatives of the fully twisted bicyclic amide 7-hypoquinuclidone are synthesized using a Schmidt–Aubé reaction. Their structures were unambiguously confirmed by X-ray diffraction analysis and extensive spectroscopic characterization. Furthermore, the stability and chemical reactivity of these anti-Bredt amides are investigated. 7-Hypoquinuclidonium tetrafluoroborate is shown to decompose to a unique nitrogen bound amide–BF_3 complex of 7-hypoquinuclidone under anhydrous conditions and to react instantaneously with water making it one of the most reactive amides known to date.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/61794, title ="Catalytic C–H bond silylation of aromatic heterocycles", author = "Toutov, Anton A. and Liu, Wen-Bo", journal = "Nature Protocols", volume = "10", number = "12", pages = "1897-1903", month = "December", year = "2015", doi = "10.1038/nprot.2015.118", issn = "1754-2189", url = "https://resolver.caltech.edu/CaltechAUTHORS:20151103-103452993", note = "© 2015 Macmillan Publishers. \n\nPublished online 29 October 2015. \n\nThis work was supported by the US National Science Foundation (NSF) under the Centers for Chemical Innovation (CCI) Center for Selective C–H Functionalization (CCHF) (grant no. CHE-1205646) and under grant no. CHE-1212767. We thank the Novartis Institutes for Biomedical Research Incorporated for the donation of samples to the CCHF. A.A.T. is grateful to the Resnick Sustainability Institute at Caltech and to Dow Chemical for a predoctoral fellowship, and to the National Sciences and Engineering Research Council of Canada (NSERC) for a Postgraduate Scholarship-Doctoral Program (PGS D) fellowship. We thank the Shanghai Institute of Organic Chemistry (SIOC) and S.-L. You (SIOC) for a postdoctoral fellowship to W.-B.L. We thank S. Virgil and the Caltech Center for Catalysis and Chemical Synthesis for access to analytical equipment. \n\nThese authors contributed equally to this work. Anton A Toutov & Wen-Bo Liu. \n\nContributions: A.A.T. and R.H.G. had the idea for and directed the investigations with W.-B.L. and B.M.S. A.A.T., W.-B.L. and K.N.B. developed the reactions, performed the experiments and analyzed the data. A.A.T. and W.-B.L. prepared the manuscript with contributions from all authors. \n\nThe authors declare no competing financial interests.", revision_no = "22", abstract = "This protocol describes a method for the direct silylation of the carbon–hydrogen (C–H) bond of aromatic heterocycles using inexpensive and abundant potassium tert-butoxide (KOt-Bu) as the catalyst. This catalytic cross-dehydrogenative coupling of simple hydrosilanes and various electron-rich aromatic heterocycles enables the synthesis of valuable silylated heteroarenes. The products thus obtained can be used as versatile intermediates, which facilitate the divergent synthesis of pharmaceutically relevant compound libraries from a single Si-containing building block. Moreover, a variety of complex Si-containing motifs, such as those produced by this protocol, are being actively investigated as next-generation therapeutic agents, because they can have improved pharmacokinetic properties compared with the original all-carbon drug molecules. Current competing methods for C–H bond silylation tend to be incompatible with functionalities, such as Lewis-basic heterocycles, that are often found in pharmaceutical substances; this leaves de novo synthesis as the principal strategy for preparation of the target sila-drug analog. Moreover, competing methods tend to be limited in the scope of hydrosilane that can be used, which restricts the breadth of silicon-containing small molecules that can be accessed. The approach outlined in this protocol enables the chemoselective and regioselective late-stage silylation of small heterocycles, including drugs and drug derivatives, with a broad array of hydrosilanes in the absence of precious metal catalysts, stoichiometric reagents, sacrificial hydrogen acceptors or high temperatures. Moreover, H_2 is the only by-product generated. The procedure normally requires 48–75 h to be completed.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/61763, title ="Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Cyclopentanones", author = "Craig, Robert A., II and Loskot, Steven A.", journal = "Organic Letters", volume = "17", number = "21", pages = "5160-5163", month = "November", year = "2015", doi = "10.1021/acs.orglett.5b02376", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20151102-100307186", note = "© 2015 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: August 17, 2015; Publication Date (Web): October 26, 2015. \n\nWe thank the NIH-NIGMS (R01GM080269 and postdoctoral fellowship F32GM073332 to A.M.H.), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. R.A.C. gratefully acknowledges the support of this work provided by a predoctoral fellowship from the National Cancer Institute of the National Institutes of Health under Award No. F31A17435. Additionally, we thank Eli Lilly (predoctoral fellowship to J.T.M.) and the Fannie and John Hertz Foundation (predoctoral fellowship to D.C.B.). \n\nR.A.C. and S.A.L. contributed equally. \n\nThe authors declare no competing financial interest.", revision_no = "27", abstract = "The first general method for the enantioselective construction of all-carbon quaternary centers on cyclopentanones by enantioselective palladium-catalyzed decarboxylative allylic alkylation is described. Employing the electronically modified (S)-(p-CF_3)_3-t-BuPHOX ligand, α-quaternary cyclopentanones were isolated in yields up to >99% with ee’s up to 94%. Additionally, in order to facilitate large-scale application of this method, a low catalyst loading protocol was employed, using as little as 0.15 mol % Pd, furnishing the product without any loss in ee.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/59300, title ="Palladium-Catalyzed Decarbonylative Dehydration for the Synthesis of α-Vinyl Carbonyl Compounds and Total Synthesis of (−)-Aspewentins A, B, and C", author = "Liu, Yiyang and Virgil, Scott C.", journal = "Angewandte Chemie International Edition", volume = "54", number = "40", pages = "11800-11803", month = "September", year = "2015", doi = "10.1002/anie.201505161", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150807-083400322", note = "© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.\n\nReceived: June 6, 2015. Article first published online: 29 July 2015. \n\nWe wish to thank the Resnick Sustainability Institute at Caltech (graduate fellowship to Y.L.), NIH (R01M080269 to B.M.S., 5R01M031332-27 to R.H.G.), the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support. Dr. David VanderVelde is acknowledged for assistance with NMR spectroscopy. Dr. Mona Shahgholi and Naseem Torian are acknowledged for assistance with high-resolution mass spectrometry. We would like to thank Prof. Richmond Sarpong of UC Berkeley for helpful discussions.", revision_no = "33", abstract = "The direct α-vinylation of carbonyl compounds to form a quaternary stereocenter is a challenging transformation. It was discovered that δ-oxocarboxylic acids can serve as masked vinyl compounds and be unveiled by palladium-catalyzed decarbonylative dehydration. The carboxylic acids are readily available through enantioselective acrylate addition or asymmetric allylic alkylation. A variety of α-vinyl quaternary carbonyl compounds are obtained in good yields, and an application in the first enantioselective total synthesis of (−)-aspewentins A, B, and C is demonstrated.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/58085, title ="Construction of Tertiary Chiral Centers by Pd-catalyzed Asymmetric Allylic Alkylation of Prochiral Enolate Equivalents", author = "Kita, Yusuke and Numajiri, Yoshitaka", journal = "Tetrahedron", volume = "71", number = "37", pages = "6349-6353", month = "September", year = "2015", doi = "10.1016/j.tet.2015.05.092", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150608-130804663", note = "© 2015 Elsevier B.V.\n\nReceived Date: 2 April 2015; Revised Date: 19 May 2015; Accepted Date: 25 May 2015; Available online 29 May 2015. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support. Y.K. expresses his special thanks to the International Engineering Science Consortium for financial support. Y.N. thanks Toray Industries Inc. for a postdoctoral fellowship. N.O. is grateful for a postdoctoral fellowship provided by Hiroshima International University. The authors thank Scott Virgil (Caltech) for instrumentation assistance and Dr. Douglas C. Behenna (Caltech) for initial experimental results.", revision_no = "31", abstract = "The palladium-catalyzed decarboxylative allylic alkylation of enol carbonates derived from lactams and ketones is described. Employing these substrates with an electronically tuned Pd catalyst system trisubstituted chiral centers are produced. These stereocenters have been previously challenging to achieve using Pd complex/chiral P–N ligand systems.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/59302, title ="Palladium(II)-Catalyzed Allylic C-H Oxidation of Hindered Substrates Featuring Tunable Selectivity Over Extent of Oxidation", author = "Xing, Xiangyou and O'Connor, Nicholas R.", journal = "Angewandte Chemie International Edition", volume = "54", number = "38", pages = "11186-11190", month = "September", year = "2015", doi = "10.1002/anie.201504007", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150807-090520766", note = "© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nReceived: May 5, 2015; Revised: June 23, 2015; Article first published online: 31 Jul 2015. \n\nThis work was supported by the NSF under the CCI Center for Selective C-H Functionalization, CHE-1205646. Additional support was provided by Caltech and Amgen. Dr. Scott C. Virgil is thanked for helpful discussions. Dr. David VanderVelde (NMR), Dr. Michael K. Takase (X-ray crystallography), and Dr. Mona Shahgholi (HRMS) are acknowledged for assistance with structural determination and characterization. Guillermo A. Guerrero-Vásquez, Lukas J.\nHilpert, and Dr. Wen-Bo Liu are acknowledged for experimental assistance.", revision_no = "28", abstract = "The use of Oxone and a palladium(II) catalyst enables the efficient allylic C-H oxidation of sterically hindered α-quaternary lactams which are unreactive under known conditions for similar transformations. This simple, safe, and effective system for C-H activation allows for unusual tunable selectivity between a two-electron oxidation to the allylic acetates and a four-electron oxidation to the corresponding enals, with the dominant product depending on the presence or absence of water. The versatile synthetic utility of both the allylic acetate and enal products accessible through this methodology is also demonstrated.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/52456, title ="Synthesis of Diverse β-Quaternary Ketones via Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Cyclic Enones", author = "Holder, Jeffrey C. and Goodman, Emmett D.", journal = "Tetrahedron", volume = "71", number = "35", pages = "5781-5792", month = "September", year = "2015", doi = "10.1016/j.tet.2014.11.048", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141208-091240402", note = "© 2014 Elsevier B.V. \n\nReceived 5 October 2014, Revised 15 November 2014, Accepted 17 November 2014, Available online 28 November 2014. \n\nDedicated to Professor Barry M. Trost upon receipt of the 2014 Tetrahedron Prize. \n\nWe are thankful to the NIH-NIGMS (R01GM080269), Caltech, Amgen, the American Chemical Society Division of Organic Chemistry (predoctoral fellowship to J.C.H.), the Swiss National Science Foundation (postdoctoral fellowship to M.G.), the Japan Society for the Promotion of Science (postdoctoral fellowship to K.K.), and the German National Academy of Sciences Leopoldine (LPDS 2011-12 postdoctoral fellowship to A.N.M.) for financial support. Prof. Theodor Agapie, Prof. Sarah E. Reisman, and Mr. Robert A. Craig, II (Caltech) are thanked for helpful discussions. Dr. David VanderVelde (Caltech) is thanked for invaluable assistance with NMR experiments and helpful discussions. The Varian 400 MHz NMR spectrometer at Caltech was purchased via an NIH grant (RR027690).", revision_no = "31", abstract = "The development and optimization of a palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enone conjugate acceptors is described. These reactions employ air-stable and readily-available reagents in an operationally simple and robust transformation that yields β-quaternary ketones in high yields and enantioselectivities. Notably, the reaction itself is highly tolerant of atmospheric oxygen and moisture and therefore does not require the use of dry or deoxygenated solvents, specially purified reagents, or an inert atmosphere. The ring size and β-substituent of the enone are highly variable, and a wide variety of β-quaternary ketones can be synthesized. More recently, the use of NH_4PF_6 has further expanded the substrate scope to include heteroatom-containing arylboronic acids and β-acyl enone substrates.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/59024, title ="Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Cyclic Electrophiles", author = "Shockley, Samantha E. and Holder, Jeffrey C.", journal = "Organic Process Research & Development", volume = "19", number = "8", pages = "974-981", month = "August", year = "2015", doi = "10.1021/acs.oprd.5b00169", issn = "1083-6160", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150728-085152188", note = "© 2015 American Chemical Society. \n\nReceived: May 28, 2015. Publication Date (Web): July 2, 2015. \n\nThe authors thank the many past and present co-workers whose efforts have made our contributions in asymmetric conjugate addition possible: Michele Gatti, Emmett D. Goodman, Kotaro Kikushima, Bin Mao, Alexander N. Marziale, and Hideki Shimizu. Support for our program has been made available from the NIH-NIGMS (R01 GM080269), Amgen, and Caltech.", revision_no = "24", abstract = "This account describes our laboratory’s efforts in the development of a palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic conjugate acceptors. Specifically, we highlight the study of this transformation in the following areas: (a) construction of all-carbon quaternary stereocenters, (b) elucidation of the reaction mechanism, (c) addition to heterocyclic acceptors to generate tertiary stereocenters, and (d) application in the synthesis of natural products.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/59860, title ="Preparation of (S)-tert-ButylPyOx and Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids", author = "Holder, Jeffrey C. and Shockley, Samantha E.", journal = "Organic Syntheses", volume = "92", pages = "247-266", month = "August", year = "2015", doi = "10.15227/orgsyn.092.0247", issn = "2333-3553", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150824-143923597", note = "© 2015 Organic Syntheses, Inc. \n\nPublished on the Web 8/7/2015.", revision_no = "18", abstract = "A. (S)-N-(1-Hydroxy-3,3-dimethylbutan-2-yl)picolinamide (2). A 1 L one-necked round-bottomed flask equipped with a 3.0 cm x 1.4 cm, egg-shaped, Teflon-coated magnetic stirring bar is sealed with a septum and connected via needle adapter to a two-tap Schlenk adapter attached to an oil bubbler and a nitrogen/vacuum manifold (Note 1). The flask is dried with a heat gun under vacuum and cooled under a stream of nitrogen. The flask is charged with 2-picolinic acid (1) (6.15 g, 50.0 mmol, 1.00 equiv) (Note 2), evacuated and back-filled with nitrogen three times, then charged with dichloromethane (300 mL, 0.17 M) (Note 3) and N-methylmorpholine (7.59 g, 8.25 mL, 75.0 mmol, 1.50 equiv). The flask is cooled in an ice/water bath and iso-butylchloroformate (6.86 mL, 7.17 g, 52.5 mmol, 1.05 equiv) is added dropwise over 30 min by syringe pump. The reaction mixture is stirred for an additional 30 min while remaining submerged in the ice/water bath. A separate 100 mL one-necked round-bottomed flask is sealed with a septum and connected via needle adapter to the two-tap Schlenk adapter and manifold, dried with a heat gun under vacuum, and allowed to cool under a stream of nitrogen. This flask is charged with (S)-tert-leucinol (6.45 g, 55.0 mmol, 1.10 equiv), dichloromethane (40 mL), and N-methylmorpholine (6.07 mL, 5.56 g, 55.0 mmol, 1.10 equiv). The resulting clear solution is taken up in a syringe and transferred dropwise using a syringe pump over the course of 1 h to the stirring reaction mixture in the ice/water bath. The cooling bath is removed, and the pale gold colored reaction mixture is stirred for an additional 6 h at 23 °C. Upon consumption of starting material (Note 4), the mixture is quenched at ambient temperature with a single addition of an aqueous solution of saturated NH_4Cl (50 mL), diluted with additional H_2O (25 mL), and transferred into a 1 L separatory funnel. The phases are separated, and the aqueous phase is extracted with CH_2Cl_2 (3 x 100 mL). The combined organic phases are washed with an aqueous solution of saturated NaHCO_3 (1 x 50 mL) and brine (1 x 50 mL). The combined organic phases are dried over Na_2SO_4 (10 g, 15 min while agitating), filtered through a M pore glass frit, and concentrated by rotary evaporation (28 °C, 15 mmHg). Excess N-methylmorpholine is further removed by placing the crude residue under high vacuum (< 12 mmHg, 12 h) to provide a pale red solid (Note 5). The crude residue is dissolved in 10 mL of acetone and purified via silica gel flash chromatography (Note 6). The combined product-containing fractions are concentrated by rotary evaporation (40 °C, 15 mmHg) to yield a solid, which is dried under high vacuum (< 12 mmHg, 12 h) to afford (S)-N-(1-hydroxy-3,3-dimethylbutan-2-yl)picolinamide (2) as a white amorphous solid (9.88-9.95 g, 44.4-44.8 mmol, 89-90% yield) (Note 7).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/58771, title ="Synthesis and exploration of electronically modified\n(R)-5,5-dimethyl-(p-CF_3)_3-i-PrPHOX in palladium-catalyzed\nenantio- and diastereoselective allylic alkylation: a practical alternative to (R)-(p-CF_3)_3-t-BuPHOX", author = "Craig, Robert A., II and Stoltz, Brian M.", journal = "Tetrahedron Letters", volume = "56", number = "32", pages = "4670-4673", month = "August", year = "2015", doi = "10.1016/j.tetlet.2015.06.039", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150706-103427588", note = "© 2015 Elsevier Ltd. Received 27 May 2015, Accepted 10 June 2015, Available online 17 June 2015.\n\nThe authors wish to thank the NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for\nfinancial support. R.A.C. gratefully acknowledges the support of this work provided by a fellowship from the National Cancer Institute of the National Institutes of Health under Award Number F31A17435.", revision_no = "24", abstract = "The synthesis of the novel electronically modified phosphinooxazoline (PHOX) ligand, (R)-5,5-dimethyl-(p-CF_3)_3-i-PrPHOX, is described. The utility of this PHOX ligand is explored in both enantio- and diastereoselective palladium-catalyzed allylic alkylations. These investigations prove (R)-5,5-dimethyl-(p-CF_3)_3-i-PrPHOX to be an effective and cost-efficient alternative to electronically modified PHOX ligands derived from the prohibitively expensive (R)-t-leucine.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/58951, title ="An Efficient Protocol for the Palladium-Catalyzed Asymmetric Decarboxylative Allylic Alkylation Using Low Palladium Concentrations and a Palladium(II) Precatalyst", author = "Marziale, Alexander N. and Duquette, Douglas C.", journal = "Advanced Synthesis and Catalysis", volume = "357", number = "10", pages = "2238-2245", month = "July", year = "2015", doi = "10.1002/adsc.201500253", issn = "1615-4150", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150720-144300390", note = "© 2015 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.\n\nReceived: March 13, 2015; Revised: May 21, 2015; Published online: July 14, 2015.\n\nWe wish to thank the NIH-NIGMS (R01M080269), Amgen, AbbVie, Boehringer Ingelheim, and Caltech for financial support. This material is based upon work supported by the German National Academy of Sciences Leopoldina under Grant No. LPDS 2011-12 (fellowship to A.N.M.). D.C.D. is grateful for financial support from the National Science Foundation (Predoctoral Research Fellowship, No. DGE-1144469). We also wish to thank the National Cancer Institute of the National Institutes of Health under Award Number F31A174359 (fellowship to R.A.C.), and the Swiss National Science Foundation (SNSF, fellowship for M.L.). Y.N. thanks Toray Industries, Inc. for a postdoctoral fellowship. Dr. Scott Virgil is acknowledged for assistance with instrumentation. Dr. John A. Enquist and Dr. Nathaniel H. Sherden are acknowledged for preliminary experimental work related to these results. Dr. Douglas C. Behenna is acknowledged for insightful discussions.", revision_no = "20", abstract = "Enantioselective catalytic allylic alkylation for the synthesis of 2-alkyl-2-allylcycloalkanones and 3,3-disubstituted pyrrolidinones, piperidinones and piperazinones has been previously reported by our laboratory. The efficient construction of chiral all-carbon quaternary centers by allylic alkylation was previously achieved with a catalyst derived in situ from zero-valent palladium sources and chiral phosphinooxazoline (PHOX) ligands. We now report an improved reaction protocol with broad applicability among different substrate classes in industry-compatible reaction media using loadings of palladium(II) acetate as low as 0.075\u2005mol% and the readily available chiral PHOX ligands. The novel and highly efficient procedure enables facile scale-up of the reaction in an economical and sustainable fashion.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/58230, title ="Exceedingly Efficient Synthesis of (±)-Grandifloracin and Acylated Analogues", author = "Bergner, Magnus and Duquette, Douglas C.", journal = "Organic Letters", volume = "17", number = "12", pages = "3008-3010", month = "June", year = "2015", doi = "10.1021/acs.orglett.5b01292", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150615-081527494", note = "© 2015 American Chemical Society.\n\nReceived: May 1, 2015. Publication Date (Web): June 10, 2015.\n\nThe authors wish to thank NSF (1265591), Amgen, and Caltech for financial support. M.B. thanks the Drug Research Academy and the Danish Cancer Society for financial support. D.C.D. (Caltech) thanks the National Science Foundation for financial support (Predoctoral Research Fellowship, No. DGE-1144469). L.C. (Caltech) is grateful to the Arthur R. Adams SURF Endowment. The Caltech Center for Catalysis and Chemical Synthesis (C3S) and especially Dr. Scott Virgil (Caltech) are acknowledged for help with chiral separation. Dr. Michael K. Takase (Caltech) is acknowledged for X-ray crystallographic structural determination.", revision_no = "19", abstract = "A highly efficient regio- and stereoselective total synthesis of (±)-grandifloracin via a tandem dearomative epoxidation/spontaneous Diels–Alder cyclodimerization from salicylic acid in only four steps is reported. The synthetic route allows for late-stage diversification of the core structure to give ready access to analogues of this promising agent against pancreatic cancer.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/50125, title ="Highly functionalized donor–acceptor cyclopropanes applied toward the synthesis of the Melodinus alkaloids", author = "Goldberg, Alexander F. G. and Craig, Robert A., II", journal = "Tetrahedron Letters", volume = "56", number = "23", pages = "2983-2990", month = "June", year = "2015", doi = "10.1016/j.tetlet.2014.09.016", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140930-130037903", note = "© 2014 Elsevier Ltd. \n\nReceived Date: 14 August 2014; Revised Date: 28 August 2014; Accepted Date: 3 September 2014; Available online 16 September 2014. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269-01),\nAmgen, and Caltech for financial support. A.F.G.G. thanks the\nNatural Sciences and Engineering Research Council (NSERC) of\nCanada for a PGS D scholarship. R.A.C. gratefully acknowledges the support of this work provided by a fellowship from the National Cancer Institute of the National Institutes of Health under Award Number F31CA174359.", revision_no = "17", abstract = "A series of highly substituted vinylcyclopropanes were prepared and examined as reaction partners in a palladium-catalyzed (3 + 2) cycloaddition with nitrostyrenes. Described herein are our efforts to synthesize an elusive 1,1-divinylcyclopropane by several distinct approaches, and to apply surrogates of this fragment toward the synthesis of the Melodinus alkaloids.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/51486, title ="Stereochemical evaluation of bis(phosphine) copper catalysts for the asymmetric alkylation of 3-bromooxindoles with α-arylated malonate esters", author = "Lee, Chung Whan and Han, Seo-Jung", journal = "Tetrahedron", volume = "71", number = "22", pages = "3666-3670", month = "June", year = "2015", doi = "10.1016/j.tet.2014.10.065", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141110-091731285", note = " © 2014 Elsevier B.V. \n\nReceived 30 September 2014; Received in revised form 24 October 2014; accepted 27 October 2014. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269-01), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. S.-J.H thanks Fulbright Commission (Foreign Student Program, No. 15111120) and the Ilju Foundation of Education & Culture (Pre-doctoral Research Fellowship) for financial support. Catalyst center (Caltech) is acknowledged for assistance with reaction screenings. Drs. Florian Vogt, Sandy Ma, Xiaoquing Han, and Shyam Krishnan are acknowledged for preliminary research.", revision_no = "29", abstract = "An improved method for the asymmetric alkylation of 3-bromooxindoles with α-arylated malonate esters is described. The asymmetric alkylation demonstrated was achieved up to 70% ee utilizing a copper(II) bis(phosphine) complex.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/55422, title ="Enantioselective Synthesis of Dialkylated N-Heterocycles by Palladium-Catalyzed Allylic Alkylation", author = "Numajiri, Yoshitaka and Jiménez-Osés, Gonzalo", journal = "Organic Letters", volume = "17", number = "5", pages = "1082-1085", month = "March", year = "2015", doi = "10.1021/ol503425t", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150302-135348269", note = "© 2015 American Chemical Society. \n\nReceived: November 25, 2014; revised: February 11, 2015. \n\nPublication Date (Web): February 25, 2015. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269 to B.M.S. and R01GM075962 to K.N.H), Amgen, the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support. Y.N. thanks Toray Industries, Inc. for a postdoctoral fellowship. G.J.-O. and K.N.H. used the Extreme Science and Engineering Discovery Environment (XSEDE) supported by a grant (OCI-1053575) along with the UCLA Institute of Digital Research and Education (IDRE). The authors are grateful to Dr. Rina Dukor (BioTools) for helpful discussions. The authors thank Scott Virgil (Caltech) for instrumentation assistance and Dr. Douglas C. Behenna (Caltech) and Mr. Beau Pritchett (Caltech) for initial experimental results.", revision_no = "35", abstract = "The enantioselective synthesis of α-disubstituted N-heterocyclic carbonyl compounds has been accomplished using palladium-catalyzed allylic alkylation. These catalytic conditions enable access to various heterocycles, such as morpholinone, thiomorpholinone, oxazolidin-4-one, 1,2-oxazepan-3-one, 1,3-oxazinan-4-one, and structurally related lactams, all bearing fully substituted α-positions. Broad functional group tolerance was explored at the α-position in the morpholinone series. We demonstrate the utility of this method by performing various transformations on our useful products to readily access a number of enantioenriched compounds.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/55758, title ="Mechanistic analysis of an asymmetric palladium-catalyzed conjugate addition of arylboronic acids to β-substituted cyclic enones", author = "Boeser, Cornelia L. and Holder, Jeffrey C.", journal = "Chemical Science", volume = "6", number = "3", pages = "1917-1922", month = "March", year = "2015", doi = "10.1039/c4sc03337j ", issn = "2041-6520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150313-143109436", note = "© 2015 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. \n\nReceived 30 Oct 2014, Accepted 13 Dec 2014, First published online 17 Dec 2014. \n\nWe gratefully acknowledge funding from the National Science Foundation under the CCI Center for Selective C–H Functionalization (CHE-1205646). C.L.B. thanks The Center for Molecular Analysis and Design (CMAD) at Stanford University for a postdoctoral fellowship. The Zare lab gratefully acknowledges financial support from a subcontract with the University of Utah (Agreement # 10029173-S2) for which the Air Force Office of Scientific Research (Grant FA9550-12-1-0481) is the prime sponsor. The Stoltz lab is thankful to the Caltech, Amgen, and the American Chemical Society Division of Organic Chemistry (predoctoral fellowship to J.C.H.) for funding. B.L.H.T. gratefully acknowledges the National Institutes of Health for a postdoctoral fellowship (F32GM106596). Computational resources were provided by the UCLA Institute for Digital Research and Education (IDRE) and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF.", revision_no = "17", abstract = "An asymmetric palladium-catalyzed conjugate addition reaction of arylboronic acids to enone substrates was investigated mechanistically. Desorption electrospray ionization coupled to mass spectrometry was used to identify intermediates of the catalytic cycle and delineate differences in substrate reactivity. Our findings provide evidence for the catalytic cycle proceeding through formation of an arylpalladium(II) cation, subsequent formation of an arylpalladium–enone complex, and, ultimately, formation of the new C–C bond. Reaction monitoring in both positive and negative ion modes revealed that 4-iodophenylboronic acid formed a relatively stable trimeric species under the reaction conditions.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/55447, title ="Selective syntheses of leuconolam, leuconoxine, and mersicarpine alkaloids from a common intermediate through regiocontrolled cyclizations by Staudinger reactions", author = "Li, Zining and Geng, Qian", journal = "Organic Chemistry Frontiers", volume = "2", number = "3", pages = "236-240", month = "March", year = "2015", doi = "10.1039/C4QO00312H", issn = "2052-4110", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150303-082954224", note = "© 2015 the Partner Organisations. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. \n\nReceived 26 Nov 2014, Accepted 20 Jan 2015, First published online 20 Jan 2015. \n\nThe NKU authors thank the National Natural Science Foundation of China, Tianjin Natural Science Foundation (grant no. 12JCZDJC26400), the ‘111’ project (B06005) of the Ministry of Education of China, and Program for New Century Excellent Talents in University for financial support. The Caltech authors wish to thank NIH-NIGMS (R01GM080269) for financial support. BPP is grateful to the National Science Foundation for a Graduate Research Fellowship. Toray is thanked for providing YN a postdoctoral opportunity\nat Caltech.", revision_no = "16", abstract = "Selective syntheses of leuconolam, leuconoxine, and mersicarpine alkaloids bearing distinctive core structures were achieved through Staudinger reactions using a common intermediate. In the key cyclization step, water functioned like a switch to control which core structure to produce. The chemistry allowed for selective syntheses of the group of alkaloids from a simple intermediate through straightforward chemical operations.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/55406, title ="Catalytic Enantioselective Construction of Quaternary Stereocenters: Assembly of Key Building Blocks for the Synthesis of Biologically Active Molecules", author = "Liu, Yiyang and Han, Seo-Jung", journal = "Accounts of Chemical Research", volume = "48", number = "3", pages = "740-751", month = "March", year = "2015", doi = "10.1021/ar5004658", issn = "0001-4842", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150302-110204535", note = "© 2015 American Chemical Society. \n\nReceived: December 29, 2014; Published: February 25, 2015. \n\nThe authors are indebted to the efforts of many members of the Stoltz Research Group whose dedicated efforts produced the chemistry described within this Account. For financial support, we thank NIH-NIGMS (Grant R01GM080269), Amgen, the Gordon and Betty Moore Foundation, Caltech, and the Resnick Sustainability Institute at Caltech (graduate fellowship to Y.L.). S.-J.H. thanks Fulbright (Foreign Student Program, No. 15111120) and the Ilju Foundation of Education & Culture (Predoctoral Research Fellowship) for financial support. Shanghai Institute of Organic Chemistry (SIOC) is thanked for a postdoctoral fellowship to W.-B.L.", revision_no = "30", abstract = "The ever-present demand for drugs with better efficacy and fewer side effects continually motivates scientists to explore the vast chemical space. Traditionally, medicinal chemists have focused much attention on achiral or so-called “flat” molecules. More recently, attention has shifted toward molecules with stereogenic centers since their three-dimensional structures represent a much larger fraction of the chemical space and have a number of superior properties compared with flat aromatic compounds. Quaternary stereocenters, in particular, add greatly to the three-dimensionality and novelty of the molecule. Nevertheless, synthetic challenges in building quaternary stereocenters have largely prevented their implementation in drug discovery. The lack of effective and broadly general methods for enantioselective formation of quaternary stereocenters in simple molecular scaffolds has prompted us to investigate new chemistry and develop innovative tools and solutions.\n\nIn this Account, we describe three approaches to constructing quaternary stereocenters: nucleophilic substitution of 3-halooxindoles, conjugate addition of boronic acids to cyclic enones, and allylic alkylation of enolates. In the first approach, malonic ester nucleophiles attack electrophilic 3-halooxindoles, mediated by a copper(II)-bisoxazoline catalyst. A variety of oxindoles containing a benzylic quaternary stereocenter can be accessed through this method. However, it is only applicable to the specialized 3,3-disubstituted oxindole system. To access benzylic quaternary stereocenters in a more general context, we turned our attention to the enantioselective conjugate addition of carbon nucleophiles to α,β-unsaturated carbonyl acceptors. We discovered that in the presence of catalytic palladium-pyridinooxazoline complex, arylboronic acids add smoothly to β-substituted cyclic enones to furnish ketones with a β-benzylic quaternary stereocenter in high yields and enantioselectivities. The reaction is compatible with a wide range of arylboronic acids, β-substituents, and ring sizes.\n\nAside from benzylic quaternary stereocenters, a more challenging motif is a quaternary stereocenter not adjacent to an aromatic group. Such centers represent more general structures in chemical space but are more difficult to form by asymmetric catalysis. To address this greater challenge, and motivated by the greater reward, we entered the field of palladium-catalyzed asymmetric allylic alkylation of prochiral enolate nucleophiles about a decade ago. On the basis of Tsuji’s work, which solved the issue of positional selectivity for unsymmetrical ketones, we discovered that the phosphinooxazoline ligand effectively rendered this reaction enantioselective. Extensive investigations since then have revealed that the reaction exhibits broad scope and accepts a range of substrate classes, each with its unique advantage in synthetic applications. A diverse array of carbonyl compounds bearing α-quaternary stereocenters are obtained in excellent yields and enantioselectivities, and more possibilities have yet to be explored. As an alternative to palladium catalysis, we also studied iridium-catalyzed asymmetric allylic alkylations that generate vicinal quaternary and tertiary stereocenters in a single transformation. Overall, these methods provide access to small molecule building blocks with a single quaternary stereocenter, can be applied to various molecular scaffolds, and tolerate a wide range of functional groups. We envision that the chemistry reported in this Account will be increasingly useful in drug discovery and design.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/51898, title ="Silylation of C–H bonds in aromatic heterocycles by an Earth-abundant metal catalyst", author = "Toutov, Anton A. and Liu, Wen-Bo", journal = "Nature", volume = "518", number = "7537", pages = "80-84", month = "February", year = "2015", doi = "10.1038/nature14126", issn = "0028-0836", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141118-102135823", note = "© 2015 Macmillan Publishers.\n\nThese authors contributed equally to this work.\n\nReceived 15 August; accepted 27 November 2014.\n\nThis work was supported by the NSF under the CCI Center for\nSelective C–H Functionalization(CHE-1205646) and under CHE-1212767, and by BP under the XC^2 initiative. We thank the Novartis Institutes for Biomedical Research\nIncorporated for the donation of samples to the CCHF. D. Morton is thanked for a donation of thenalidine. A.A.T. is grateful to the Resnick Sustainability Institute at\nCaltech and to Dow Chemical for a predoctoral fellowship, and to NSERC for a PGS D fellowship. The Shanghai Institute of Organic Chemistry (SIOC) and S.-L. You are\nthanked for a postdoctoral fellowship to W.-B.L. We thank S. Virgil and the Caltech Center for Catalysis and Chemical Synthesis for access to analytical equipment. D.Vandervelde is acknowledged for assistance with NMR interpretation. N. Dalleska is thanked for assistance with ICP-MS trace metal analysis. M. Shahgoli and N. Torian are\nacknowledged for assistance with high-resolution mass spectrometry.\n\nA.A.T., W.-B.L. and K.N.B. developed the reactions, performed the experiments and analysed data. A.F. analysed data. A.A.T and R.H.G. had the idea for and directed the investigations with W.-B.L. and B.M.S. A.A.T. and W.-B.L. prepared the manuscript with contributions from all authors. All authors contributed to discussions.", revision_no = "39", abstract = "Heteroaromatic compounds containing carbon–silicon (C–Si) bonds are of great interest in the fields of organic electronics and photonics1, drug discovery, nuclear medicine and complex molecule synthesis, because these compounds have very useful physicochemical properties. Many of the methods now used to construct heteroaromatic C–Si bonds involve stoichiometric reactions between heteroaryl organometallic species and silicon electrophiles or direct, transition-metal-catalysed intermolecular carbon–hydrogen (C–H) silylation using rhodium or iridium complexes in the presence of excess hydrogen acceptors. Both approaches are useful, but their limitations include functional group incompatibility, narrow scope of application, high cost and low availability of the catalysts, and unproven scalability. For this reason, a new and general catalytic approach to heteroaromatic C–Si bond construction that avoids such limitations is highly desirable. Here we report an example of cross-dehydrogenative heteroaromatic C–H functionalization catalysed by an Earth-abundant alkali metal species. We found that readily available and inexpensive potassium tert-butoxide catalyses the direct silylation of aromatic heterocycles with hydrosilanes, furnishing heteroarylsilanes in a single step. The silylation proceeds under mild conditions, in the absence of hydrogen acceptors, ligands or additives, and is scalable to greater than 100 grams under optionally solvent-free conditions. Substrate classes that are difficult to activate with precious metal catalysts are silylated in good yield and with excellent regioselectivity. The derived heteroarylsilane products readily engage in versatile transformations enabling new synthetic strategies for heteroaromatic elaboration, and are useful in their own right in pharmaceutical and materials science applications.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/54071, title ="Enantioselective Synthesis of α‑Quaternary Mannich Adducts by Palladium-Catalyzed Allylic Alkylation: Total Synthesis of (+)-Sibirinine", author = "Numajiri, Yoshitaka and Pritchett, Beau P.", journal = "Journal of the American Chemical Society", volume = "137", number = "3", pages = "1040-1043", month = "January", year = "2015", doi = "10.1021/ja512124c", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150126-101327424", note = "© 2015 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: November 26, 2014. Publication Date (Web): January 11, 2015. \n\nThis manuscript is dedicated to Professor Teruaki Mukaiyama\nin celebration of the 40th anniversary of the Mukaiyama Aldol reaction. The authors wish to thank NIH-NIGMS\n(R01GM080269), Amgen, the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical\nSynthesis, and Caltech for financial support. Y.N. thanks Toray Industries Inc. for a postdoctoral fellowship. B.P.P. thanks the NSF for a predoctoral fellowship. K.C. acknowledges the Japan Society for the Promotion of Science for a postdoctoral fellowship. The authors thank Mona Shahgholi and Naseem Torian for mass spectrometry assistance and Dr. Scott Virgil (Caltech) for instrumentation assistance.", revision_no = "30", abstract = "A catalytic enantioselective method for the synthesis of α-quaternary Mannich-type products is reported. The two-step sequence of (1) Mannich reaction followed by (2) decarboxylative enantioselective allylic alkylation serves as a novel strategy to in effect access asymmetric Mannich-type products of “thermodynamic” enolates of substrates possessing additional enolizable positions and acidic protons. Palladium-catalyzed decarboxylative allylic alkylation enables the enantioselective synthesis of five-, six-, and seven-membered ketone, lactam, and other heterocyclic systems. The mild reaction conditions are notable given the acidic free N–H groups and high functional group tolerance in each of the substrates. The utility of this method is highlighted in the first total synthesis of (+)-sibirinine.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/51824, title ="Enantioselective Synthesis of α-Secondary and α-Tertiary Piperazin-2-ones and Piperazines by Catalytic Asymmetric Allylic Alkylation", author = "Korch, Katerina M. and Eidamshaus, Christian", journal = "Angewandte Chemie International Edition", volume = "54", number = "1", pages = "179-183", month = "January", year = "2015", doi = "10.1002/anie.201408609", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141117-092808886", note = "© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.\n\nReceived: August 27, 2014,\nArticle first published online: 7 NOV 2014.\n\nWe wish to thank the NIH-NIGMS (R01GM080269) for financial support. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1144469 (fellowship to K.M.K.). We also wish to thank the Deutsche Forschungsgemeinschaft (DFG postdoctoral fellowship to C.E.), Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. Corey Reeves is acknowledged for providing allyl cyanoformate and for insightful discussions. Douglas Duquette is acknowledged for providing allyl 1H-imidazole-1-carboxylate reagents and for insightful discussions. Scott Virgil is acknowledged for assistance with instrumentation and insightful discussions.", revision_no = "35", abstract = "The asymmetric palladium-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2-ones allows the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogues. The introduction of these chiral tertiary piperazines resulted in imatinib analogues which exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/52292, title ="Evolution of a Unified, Stereodivergent Approach to the Synthesis of Communesin F and Perophoramidine", author = "Han, Seo-Jung and Vogt, Florian", journal = "Journal of Organic Chemistry", volume = "80", number = "1", pages = "528-547", month = "January", year = "2015", doi = "10.1021/jo502534g", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141202-144818205", note = "© 2014 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: November 5, 2014. Publication Date (Web): November 17, 2014. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. S.-J.H. thanks Fulbright (Foreign Student\nProgram, No. 15111120) and the Ilju Foundation of Education\n& Culture (Predoctoral Research Fellowship) for financial\nsupport. F.V. thanks the German Academic Exchange Service\n(DAAD) for a postdoctoral fellowship. J.A.M. is grateful for a fellowship by Bristol-Myers Squibb and Amgen. S.K. thanks California TRDRP for financial support (postdoctoral fellowship 14FT-0002). M.G. is grateful to the Swiss National Science Foundation for financial support (postdoctoral fellowship). Dr. David VanderVelde (Caltech) is gratefully acknowledged for assistance with the characterization of compounds by NMR spectroscopy. Lawrence Henling (Caltech) is acknowledged for X-ray crystallographic structural determination. The authors are\nthankful to Dr. Ryan Zeidan, Dr. Sandy Ma, and Mr. Chung\nWhan Lee for experimental assistance.", revision_no = "42", abstract = "Expedient synthetic approaches to the highly functionalized polycyclic alkaloids communesin F and perophoramidine are described using a unified approach featuring a key decarboxylative allylic alkylation to access a crucial and highly congested 3,3-disubstituted oxindole. Described are two distinct, stereoselective alkylations that produce structures in divergent diastereomeric series possessing the critical vicinal all-carbon quaternary centers needed for each synthesis. Synthetic studies toward these challenging core structures have revealed a number of unanticipated modes of reactivity inherent to these complex alkaloid scaffolds. Additionally, several novel and interesting intermediates en route to the target natural products, such as an intriguing propellane hexacyclic oxindole encountered in the communesin F sequence, are disclosed. Indeed, such unanticipated structures may prove to be convenient strategic intermediates in future syntheses.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/52799, title ="A Catalytic, Enantioselective Formal Synthesis of (+)-Dichroanone and (+)-Taiwaniaquinone H", author = "Shockley, Samantha E. and Holder, Jeffrey C.", journal = "Organic Letters", volume = "16", number = "24", pages = "6362-6365", month = "December", year = "2014", doi = "10.1021/ol5031537", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141215-090404543", note = "© 2014 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: October 28, 2014. Publication Date (Web): December 9, 2014. \n\nThe authors thank NIH-NIGMS (B.M.S., R01 GM080269), Caltech, and the American Chemical Society Division of Organic\nChemistry (predoctoral fellowship J.C.H) for financial support.\nDr. Scott Virgil is thanked for helpful discussions and assistance\nwith chiral chromatography. Dr. David VanderVelde of the\nCaltech NMR facility is thanked for invaluable assistance with\nNMR experiments and helpful discussions. Lawrence Henling\nand Dr. Michael K. Takase (Caltech) are gratefully acknowledged\nfor X-ray crystallographic structural determination. Dr. Mona\nShahgholi is thanked for mass spectroscopy determination.\nNiklas B. Thompson is thanked for his assistance with\ncrystallographic and Hammett plot analysis. The Bruker\nKAPPA APEXII X-ray diffractometer was purchased via an\nNSF CRIF:MU award to Caltech. The Varian 400 MHz NMR\nspectrometer at Caltech was purchased via an NIH grant\n(RR027690).", revision_no = "21", abstract = "A catalytic, enantioselective formal synthesis of (+)-dichroanone and (+)-taiwaniaquinone H is reported. The all-carbon quaternary stereocenter was constructed by asymmetric conjugate addition catalyzed by a palladium(II) (S)-tert-butylpyridinooxazoline complex. The unexpected formation of a [3.2.1] bicyclic intermediate required the identification of a new route. Analysis of the Hammett constants for para-substituted arenes enabled the rational design of a highly enantioselective conjugate addition substrate that led to the completion of the formal synthesis.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/50577, title ="A new method for the cleavage of nitrobenzyl amides and ethers", author = "Han, Seo-Jung and de Melo, Gabriel Fernando", journal = "Tetrahedron Letters", volume = "55", number = "47", pages = "6467-6469", month = "November", year = "2014", doi = "10.1016/j.tetlet.2014.10.006", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141020-152334369", note = "© 2014 Elsevier Ltd. \n\nReceived 12 September 2014. Revised 30 September 2014. Accepted 1 October 2014. Available online 6 October 2014. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269-01), Amgen, and Caltech for financial support. S.-J.H. thanks Fulbright\n(Foreign Student Program, No. 15111120) and the Ilju Foundation of Education & Culture (Pre-doctoral Research Fellowship) for financial support.", revision_no = "31", abstract = "A mild and efficient o- and p-nitrobenzyl cleavage protocol was developed. o- and p-nitrobenzyl groups were easily removed from a variety of substrates using 20% aqueous NaOH in methanol at 75 °C, presumably via oxidation at the benzylic position by oxygen dissolved in the solution. These easily introducible and removable nitrobenzyl groups can serve as valuable protecting groups for the synthesis of multifunctional, complex molecules.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/52797, title ="Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation", author = "Liu, Yiyang and Liniger, Marc", journal = "Beilstein Journal of Organic Chemistry", volume = "10", pages = "2501-2512", month = "October", year = "2014", doi = "10.3762/bjoc.10.261", issn = "1860-5397", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141215-084337170", note = "© 2014, Liu et al; licensee Beilstein-Institut. This is an Open Access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (http://www.beilstein-journals.org/bjoc).\n\nReceived: 11 August 2014. Accepted: 09 October 2014. Published: 28 October 2014. Associate Editor: S. Bräse. \n\nWe are grateful to NIH (R01GM080269), Amgen, the Gordon\nand Betty Moore Foundation, and Caltech for funding. We also\nthank the Caltech Minorities Undergraduate Research Fellowship program, PREM program, Eli Lilly, the Resnick Sustainability Institute at Caltech (fellowship for Y. L.), and the Swiss National Science Foundation (SNSF, fellowship for M. L.). Dr. Michael L. Krout and Dr. David E. White are acknowledged for preliminary experimental work related to their results. Dr. Michael Takase (Caltech) and Larry Henling (Caltech) are gratefully acknowledged for X-ray crystallographic structural determination.", revision_no = "13", abstract = "Pd-catalyzed enantioselective alkylation in conjunction with further synthetic elaboration enables the formal total syntheses of a number of “classic” natural product target molecules. This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods will impact both academic and industrial settings, where the synthesis of stereogenic quaternary carbons is a continuing challenge.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/50396, title ="The Total Syntheses of Basiliolide C, epi-Basiliolide C, and Protecting-Group-Free Total Syntheses of Transtaganolides C and D", author = "Gordon, Jonny R. and Nelson, Hosea M.", journal = "Journal of Organic Chemistry", volume = "79", number = "20", pages = "9740-9747", month = "October", year = "2014", doi = "10.1021/jo501924u", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141015-093052860", note = "© 2014 American Chemical Society.\n\nReceived: August 19, 2014.\nPublication Date (Web): September 22, 2014.\n\nThe authors wish to thank the NSF (Award 1265591), Amgen,\nthe Gordon and Betty Moore Foundation, and Caltech for\nfinancial support. J.R.G. thanks the Rose Hill Foundation for a predoctoral fellowship. H.M.N. thanks the NSF and Ford\nFoundation for predoctoral fellowships. Prof. Giovanni\nAppendino and Prof. Eduardo Muñoz are acknowledged for\nthe biological testing of synthetically derived transtaganolide C. Dr. Kei Murakami is acknowledged for his contribution to the preparation of racemic transtaganolides C and D. Dr. Alexander F. G. Goldberg and Mr. Robert A. Craig II are acknowledged for useful discussions regarding synthetic strategies. Ms. Katerina M. Korch and Mr. Corey M. Reeves are acknowledged for assistance in manuscript preparation. Dr. David Vander-Velde is acknowledged for NMR assistance.", revision_no = "20", abstract = "The total syntheses of basiliolide C and previously unreported epi-basiliolide C are achieved by an Ireland–Claisen/Diels–Alder cascade. The development of a palladium catalyzed cross-coupling of methoxy alkynyl zinc reagents allows for the protecting-group-free syntheses of transtaganolides C and D. Syntheses of transtaganolides C and D are accomplished in a single operation to generate three rings, two all-carbon quaternary centers, and four tertiary stereocenters from a monocyclic, achiral precursor.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/48342, title ="Asymmetric synthesis of QUINAP via dynamic kinetic resolution", author = "Bhat, Vikram and Virgil, Scott C.", pages = "ORGN 44", month = "August", year = "2014", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140811-150157474", note = "© 2014 American Chemical Society.", revision_no = "8", abstract = "A Pd-catalyzed, atroposelective C-P coupling process has been developed for the asym. synthesis of QUINAP and its derivs. in high enantiomeric excess. Bromide, triflate (OTf) and 4-methanesulfonylbenzenesulfonate (OSs) precursors were studied, leading in the case of the triflate to a novel dynamic kinetic resoln. involving isomerization of an arylpalladium intermediate. The operationally simple methods described in this communication afford these important ligands in good to high yields and selectivity using low catalyst loading (≤3 mol % Pd).", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/48343, title ="Development and application of a palladium-\u200bcatalyzed enantioselective conjugate addition", author = "Holder, Jeffrey C. and Shockley, Samantha E.", pages = "ORGN 42", month = "August", year = "2014", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140811-150326033", note = "© 2014 American Chemical Society.", revision_no = "12", abstract = "The first enantioselective palladium-catalyzed, asym. construction of all-carbon quaternary stereocenters via 1, 4-addn. of arylboronic acids to cyclic, β-substituted enones is reported. A wide range of arylboronic acids and cyclic enones are reacted utilizing a catalyst prepd. from palladium(II) trifluoroacetate and a chiral pyridinooxazoline ligand to yield enantioenriched products bearing benzylic stereocenters. Recently, this methodol. has been expanded to support the reaction of heterocyclic chromone and 4-quinolone conjugate acceptors. Notably, this transformation is insensitive to air or moisture, providing a practical and operationally simple method of synthesizing enantioenriched stereocenters. The application of this reaction toward the total syntheses of members of the taiwaniaquinone sesquiterpenoid family of natural products is discussed.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/45060, title ="Palladium-catalyzed decarboxylative allylic alkylation of diastereomeric β-ketoesters", author = "Ma, Sandy and Reeves, Corey M.", journal = "Tetrahedron", volume = "70", number = "27-28", pages = "4208-4212", month = "July", year = "2014", doi = "10.1016/j.tet.2014.03.042", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140421-084129624", note = "© 2014 Elsevier Ltd. \n\nReceived 21 February 2014; Received in revised form 10 March 2014; Accepted 12 March 2014; Available online 18 March 2014. \n\nDedicated to Professor Sarah Reisman on receipt of the Tetrahedron Young Investigator Award. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Abbott Laboratories (_100001316), Amgen (_100002429),Merck, Bristol-Myers Squibb (_100002491), Boehringer Ingelheim (_100001003), the Gordon and Betty Moore Foundation (_100000936) and Caltech for financial support. C.M.R. gratefully acknowledges the Rose Hill Foundation for pre-doctoral funding. R.A.C. gratefully acknowledges the support of this work provided by a fellowship from the National Cancer Institute of the National Institutes of Health (_100000002) under Award Number F31CA174359. Mr. Lawrence Henling and Dr. Michael Day are gratefully acknowledged for Xray crystallographic structural determination. The Bruker KAPPA APEXII X-ray diffractometer was purchased via an NSF CRIF:MU award to the California Institute of Technology, CHE-0639094.", revision_no = "33", abstract = "The palladium-catalyzed decarboxylative allylic alkylation of diastereomeric β-ketoesters derived from 4-tert-butylcyclohexanone is described. These experiments were performed to elucidate our understanding of stereoablative enantioconvergent catalysis. A detailed analysis of the product distribution, including stereochemical outcome of the products, is included. These studies also reveal an interesting example of selectivity that is governed by competing modes of substrate and catalyst control.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/46275, title ="A Diastereodivergent Synthetic Strategy for the Syntheses of Communesin F and Perophoramidine", author = "Han, Seo-Jung and Vogt, Florian", journal = "Organic Letters", volume = "16", number = "12", pages = "3316-3319", month = "June", year = "2014", doi = "10.1021/ol5013263", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140616-094313057", note = "© 2014 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: May 8, 2014. Publication Date (Web): June 9, 2014. \nThe authors wish to thank NIH-NIGMS (R01GM080269),\nAmgen, the Gordon and Betty Moore Foundation, and Caltech\nfor financial support. S.-J.H. thanks Fulbright (Foreign Student\nProgram, No. 15111120) and the Ilju Foundation of Education\n& Culture (Predoctoral Research Fellowship) for financial\nsupport. F.V. thanks the German Academic Exchange Service\n(DAAD) (postdoctoral fellowship). S.K. thanks California\nTRDRP for financial support (postdoctoral fellowship 14FT-\n0002). J.A.M. is grateful for a fellowship by Bristol-Myers Squibb and Amgen. M.G. is grateful to the Swiss National Science Foundation for financial support (postdoctoral fellowship). Dr. David VanderVelde (Caltech) is gratefully acknowledged for assistance with the characterization of compounds by NMR spectroscopy. Lawrence Henling (Caltech) is acknowledged for X-ray crystallographic structural determination.", revision_no = "25", abstract = "An efficient, unified, and stereodivergent approach toward communesin F and perophoramidine was examined. The C(3) all-carbon quaternary center of an oxindole was smoothly constructed by base-promoted indolone-malonate alkylation chemistry. The complementary relative stereochemistry of the crucial vicinal quaternary centers found in communesin F and perophoramidine was selectively installed by substrate-controlled decarboxylative allylic alkylations.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/45479, title ="Biosynthesis and Chemical Synthesis of Presilphiperfolanol Natural Products", author = "Hong, Allen Y. and Stoltz, Brian M.", journal = "Angewandte Chemie International Edition", volume = "53", number = "21", pages = "5248-5260", month = "May", year = "2014", doi = "10.1002/anie.201309494", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140505-091759313", note = "© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nArticle first published online: 25 April 2014; Manuscript Received: 31 October 2013.\n\nWe thank Dr. Scott Virgil, Prof. Sarah Reisman, Dr. Douglas\nBehenna, Dr. Mike Krout, Dr. Thomas Jensen, Dr. Phil Kun-\nLiang Wu, Dr. Alex Marziale, Dr. Jimin Kim, Douglas\nDuquette, Nick O'Connor, Jeffrey Holder, Nathan Bennett,\nand the reviewers for helpful discussions and suggestions. We thank NIH-NIGMS (R01GM080269), Roche, Abbott Laboratories, Amgen, Boehringer Ingelheim, the Gordon and Betty Moore Foundation, and Caltech for awards and financial\nsupport\n\n", revision_no = "19", abstract = "Presilphiperfolanols constitute a family of biosynthetically important sesquiterpenes which can rearrange to diverse sesquiterpenoid skeletons. While the origin of these natural products can be traced to simple linear terpene precursors, the details of the enzymatic cyclization mechanism that forms the stereochemically dense tricyclic skeleton has required extensive biochemical, computational, and synthetic investigation. Parallel efforts to prepare the unique and intriguing structures of these compounds by total synthesis have also inspired novel strategies, thus resulting in four synthetic approaches and two completed syntheses. While the biosynthesis and chemical synthesis studies performed to date have provided much insight into the role and properties of these molecules, emerging questions regarding the biosynthesis of newer members of the family and subtle details of rearrangement mechanisms have yet to be explored.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/45195, title ="Development of (Trimethylsilyl)ethyl Ester Protected Enolates and Applications in Palladium-Catalyzed Enantioselective Allylic Alkylation: Intermolecular Cross-Coupling of Functionalized Electrophiles", author = "Reeves, Corey M. and Behenna, Douglas C.", journal = "Organic Letters", volume = "16", number = "9", pages = "2314-2317", month = "May", year = "2014", doi = "10.1021/ol500355z", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140424-145313873", note = "© 2014 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: February 3, 2014; Publication Date (Web): April 11, 2014. \n\nThe authors declare no competing financial interest. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support. C.M.R. thanks the Rose Hills Foundation for a predoctoral fellowship. The authors thank Scott Virgil (Caltech) for helpful discussions and instrumentation assistance. Rob Craig (Caltech) and Dr. Allen Hong (Caltech) are thanked for helpful discussion.", revision_no = "25", abstract = "The development of (trimethylsilyl)ethyl ester protected enolates is reported. The application of this class of compounds in palladium-catalyzed asymmetric allylic alkylation is explored, yielding a variety of α-quaternary six- and seven-membered ketones and lactams. Independent coupling partner synthesis engenders enhanced allyl substrate scope relative to traditional β-ketoester substrates; highly functionalized α-quaternary ketones generated by the union of (trimethylsilyl)ethyl β-ketoesters and sensitive allylic alkylation coupling partners serve to demonstrate the utility of this method for complex fragment coupling.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/44216, title ="Stereoselective Lewis Acid Mediated (3+2) Cycloadditions of N-H- and N-Sulfonylaziridines with Heterocumulenes", author = "Craig, Robert A., II and O'Connor, Nicholas R.", journal = "Chemistry: a European Journal", volume = "20", number = "16", pages = "4806-4813", month = "April", year = "2014", doi = "10.1002/chem.201303699", issn = "0947-6539", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140310-100420677", note = "© 2013 Wiley-VCH Verlag GmbH & Co. \n\nReceived: September 21, 2013. Article first published online: 6 Mar. 2014. \n\nThe authors wish to thank NIH-NIGMS (R01M080269-01), Amgen, and Caltech for financial support. R.A.C. gratefully acknowledges the support of this work provided by a fellowship from the National Cancer Institute of the National Institutes of\nHealth under Award Number F31A174359. A.F.G.G. thanks the\nNatural Sciences and Engineering Research Council (NSERC) of Canada for a PGS D scholarship. L. Henling (Caltech) and Dr. M. Takase (Caltech) are gratefully acknowledged for X-ray crystallographic structural determination. The Bruker KAPPA APEXII X-ray diffractometer was purchased via an NSF CRIF:MU award to the California Institute of Technology, CHE-0639094.", revision_no = "36", abstract = "Alkyl and aryl isothiocyanates and carbodiimides are effective substrates in (3+2) cycloadditions with N-sulfonyl-2-substituted aziridines and 2-phenylaziridine for the synthesis of iminothiazolidines and iminoimidazolidines. Additionally, the stereoselective (3+2) cycloaddition of N-H- and N-sulfonylaziridines with isothiocyanates can be accomplished, allowing for the synthesis of highly enantioenriched iminothiazolidines. Evidence for an intimate ion-pair mechanism is presented herein in the context of these chemo-, regio-, and diastereoselective transformations. The demonstrated ability to remove the sulfonyl group from the heterocyclic products displays the utility of these compounds for further derivatization and application.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/45393, title ="Toward a Symphony of Reactivity: Cascades Involving Catalysis and Sigmatropic Rearrangements", author = "Jones, Amanda C. and May, Jeremy A.", journal = "Angewandte Chemie International Edition", volume = "53", number = "10", pages = "2556-2591", month = "March", year = "2014", doi = "10.1002/anie.201302572 ", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140501-092433445", note = "© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nReceived: March 27, 2013; Published online: February 12, 2014. \n\nWe thank Dr. Wen-Bo Liu and Nathan Bennett for helpful comments and editing. We also thank NIH-NIGMS (R01GM080269), Amgen, Abbott, Boehringer Ingelheim, ACS Organic Division (fellowship for J.A.M), Bristol-Meyers Squibb (fellowship for J.A.M), Pfizer-UNCF (fellowship for R.S.), and Caltech for financial support. A.C.J. thanks Wake Forest University for start-up support and NIH-NRSA (F32GM082000) for support of a postdoctoral fellowship.", revision_no = "19", abstract = "Catalysis and synthesis are intimately linked in modern organic chemistry. The synthesis of complex molecules is an ever evolving area of science. In many regards, the inherent beauty associated with a synthetic sequence can be linked to a certain combination of the creativity with which a sequence is designed and the overall efficiency with which the ultimate process is performed. In synthesis, as in other endeavors, beauty is very much in the eyes of the beholder.† It is with this in mind that we will attempt to review an area of synthesis that has fascinated us and that we find extraordinarily beautiful, namely the combination of catalysis and sigmatropic rearrangements in consecutive and cascade sequences.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/43756, title ="Gas Phase Production and Loss of Isoprene Epoxydiols", author = "Bates, Kelvin H. and Crounse, John D.", journal = "Journal of Physical Chemistry A", volume = "118", number = "7", pages = "1237-1246", month = "February", year = "2014", doi = "10.1021/jp4107958", issn = "1089-5639", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140210-145231305", note = "© 2014 American Chemical Society. \n \nReceived: November 1, 2013; Revised: January 28, 2014; Published: January 29, 2014. \n\nThe authors would like to thank Prof. Jason D. Surratt for correspondence regarding the synthesis of IEPOX and the National Science Foundation (AGS 1240604) for their support of this research.", revision_no = "31", abstract = "Isoprene epoxydiols (IEPOX) form in high yields from the OH-initiated oxidation of isoprene under low-NO conditions. These compounds contribute significantly to secondary organic aerosol formation. Their gas-phase chemistry has, however, remained largely unexplored. In this study, we characterize the formation of IEPOX isomers from the oxidation of isoprene by OH. We find that cis-β- and trans-β-IEPOX are the dominant isomers produced, and that they are created in an approximate ratio of 1:2 from the low-NO oxidation of isoprene. Three isomers of IEPOX, including cis-β- and trans-β, were synthesized and oxidized by OH in environmental chambers under high- and low-NO conditions. We find that IEPOX reacts with OH at 299 K with rate coefficients of (0.84 ± 0.07) × 10^(–11), (1.52 ± 0.07) × 10^(–11), and (0.98 ± 0.05) × 10^(–11) cm^3 molecule^(–1) s^(–1) for the δ1, cis-β, and trans-β isomers. Finally, yields of the first-generation products of IEPOX + OH oxidation were measured, and a new mechanism of IEPOX oxidation is proposed here to account for the observed products. The substantial yield of glyoxal and methylglyoxal from IEPOX oxidation may help explain elevated levels of those compounds observed in low-NO environments with high isoprene emissions.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/43829, title ="Angiotensin II Receptor Type 1—A Novel Target for Preventing Neonatal Meningitis in Mice by Escherichia coli K1", author = "Krishnan, Subramanian and Shanmuganathan, Muthusamy V.", journal = "Journal of Infectious Diseases", volume = "209", number = "3", pages = "409-419", month = "February", year = "2014", doi = "10.1093/infdis/jit499", issn = "0022-1899", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140214-093051277", note = "© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. \n\nReceived 30 May 2013; accepted 13 August 2013; electronically published 16 September 2013. \n\nThis work was supported by the National Institutes of Health (grants AI40567 and NS73115 to N. V. P.).", revision_no = "20", abstract = "The increasing incidence of Escherichia coli K1 meningitis due to escalating antibiotic resistance warrants alternate treatment options to prevent this deadly disease. We screened a library of small molecules from the National Institutes of Health clinical collection and identified telmisartan, an angiotensin II receptor type 1 (AT1R) blocker, as a potent inhibitor of E. coli invasion into human brain microvascular endothelial cells (HBMECs). Immunoprecipitation studies revealed that AT1R associates with endothelial cell gp96, the receptor in HBMECs for E. coli outer membrane protein A. HBMECs pretreated with telmisartan or transfected with AT1R small interfering RNA were resistant to E. coli invasion because of downregulation of protein kinase C-α phosphorylation. Administration of a soluble derivative of telmisartan to newborn mice before infection with E. coli prevented the onset of meningitis and suppressed neutrophil infiltration and glial cell migration in the brain. Therefore, telmisartan has potential as an alternate treatment option for preventing E. coli meningitis.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/43475, title ="Palladium-Catalyzed Decarbonylative Dehydration of Fatty Acids for the Production of Linear Alpha Olefins", author = "Liu, Yiyang and Kim, Kelly E.", journal = "Advanced Synthesis and Catalysis", volume = "356", number = "1", pages = "130-136", month = "January", year = "2014", issn = "1615-4150", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140122-135551444", note = "© 2014 Wiley-VCH Verlag GmbH & Co. \n\nReceived: December 9, 2013; Published online: January 13, 2014. \n\nThe authors wish to thank the Resnick Sustainability Institute at Caltech (graduate fellowship to Y.L.), BP (postdoctoral fellowship to A.F. under the XC2 program), NIH-NIGMS (R01GM080269, B.M.S.), NIH (NIH 5R01GM031332-27, R.H.G.), the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support. Materia, Inc. is thanked for the generous donation of ruthenium catalysts. Dr. David Vander-Velde is acknowledged for NMR spectroscopy assistance. Dr. Mona Shahgholi and Naseem Torian are acknowledged for high-resolution mass spectrometry assistance. Dr. Scott Virgil is acknowledged for helpful discussions.", revision_no = "33", abstract = "A highly efficient palladium-catalyzed decarbonylative dehydration reaction of carboxylic acids is reported. This method transforms abundant and renewable even-numbered natural fatty acids into valuable and expensive odd-numbered alpha olefins. Additionally, the chemistry displays a high functional group tolerance. The process employs a low loading of palladium catalyst and proceeds under solvent-free and relatively mild conditions.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/54062, title ="Alkylations of Enols and Enolates", author = "Stoltz, B. M. and Bennett, N. B.", volume = "3", pages = "1-55", month = "January", year = "2014", doi = "10.1016/B978-0-08-097742-3.00301-3", isbn = "978-0-08-097743-0", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150126-091231023", note = "© 2014 Elsevier Ltd.", revision_no = "12", abstract = "Enolate alkylation, the nucleophilic substitution of electrophilic alkylating reagents by carbon nucleophiles generated from the adeprotonation\nof carbonyl compounds, is one among the most fundamental and important methods for the construction of\ncarbon–carbon bonds adjacent to a carbonyl group. Over the past fifty years, this methodology has evolved into a highly selective,\nefficient, and essential technique integral to the practitioners of pharmaceutical industry, chemical biology, and academic organic\nsynthesis.\nSince the previous publication of Comprehensive Organic Synthesis in 1991, a field-wide explosion of interest in catalysis has\nsparked the development of numerous metal and metal-free catalytic alkylation methods. These advances have introduced new\nmethods for enolate formation, expanded substrate scope, and enabled highly stereoselective α-alkylations. New techniques allow\nelaboration of a diverse array of small molecules and have made enolate alkylation one of the most important methods for\nasymmetric carbon–carbon bond formation.\nOwing to the overwhelming wealth of literature on carbonyl chemistry, attempt has been made to narrowly define ‘enolate\nalkylation’ to encompass only the reactions of enolates with sp^3-hybridized carbon electrophiles. Aldol reactions, conjugate\nadditions, arylations, and functionalizations of enamines and metalloenamines will be addressed in other chapters of this\ncompendium.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/42896, title ="A Unified Approach to the Daucane and Sphenolobane Bicyclo[5.3.0]decane Core: Enantioselective Total Syntheses of Daucene, Daucenal, Epoxydaucenal\u2005B, and 14-para-Anisoyloxydauc-4,8-diene", author = "Bennett, Nathan B. and Stoltz, Brian M.", journal = "Chemistry: a European Journal", volume = "19", number = "52", pages = "17745-17750", month = "December", year = "2013", doi = "10.1002/chem.201302353", issn = "0947-6539", url = "https://resolver.caltech.edu/CaltechAUTHORS:20131209-101849386", note = "© 2013 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim. \n\nReceived: June 19, 2013. Article first published online: 2 Dec. 2013. \n\nThe authors wish to thank the NIH-NIGMS (R01 M080269), Amgen, the Gordon and Betty Moore Foundation, the ARCS foundation, and Caltech for awards and financial support. Dr. Allen Hong, Dr. Thomas Jensen, and Prof. Sarah Reisman are acknowledged for helpful discussions and suggestions. Dr. David VanderVelde and Dr. Scott Ross are acknowledged\nfor NMR spectroscopic assistance. Dr. Mona Shahgoli and\nNaseem Torian are acknowledged for high-resolution mass spectrometry assistance.", revision_no = "25", abstract = "Access to the bicyclo[5.3.0]decane core found in the daucane and sphenolobane terpenoids via a key enone intermediate enables the enantioselective total syntheses of daucene, daucenal, epoxydaucenal\u2005B, and 14-para-anisoyloxydauc-4,8-diene. Central aspects include a catalytic asymmetric alkylation followed by a ring contraction and ring-closing metathesis to generate the five- and seven-membered rings, respectively.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/43225, title ="Enantio-, Diastereo-, and Regioselective Iridium-Catalyzed Asymmetric Allylic Alkylation of Acyclic β-Ketoesters", author = "Liu, Wen-Bo and Reeves, Corey M.", journal = "Journal of the American Chemical Society", volume = "135", number = "46", pages = "17298-17301", month = "November", year = "2013", doi = "10.1021/ja4097829 ", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20140106-104251997", note = "© 2013 American Chemical Society.\n\nReceived: September 20, 2013; Published: October 28, 2013.\n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, the Caltech\nCenter for Catalysis and Chemical Synthesis, and Caltech for financial support. Shanghai Institute of Organic Chemistry\n(SIOC) is thanked for a postdoctoral fellowship to W.-B.L. Lawrence Henling is acknowledged for X-ray crystallographic\nstructural determination. We thank the reviewers for the valuable suggestions about the Hammett correlation and Brown\nσ+ constants.", revision_no = "24", abstract = "The first regio-, diastereo-, and enantioselective allylic alkylation of acyclic β-ketoesters to form vicinal tertiary and all-carbon quaternary stereocenters is reported. Critical to the successful development of this method was the employment of iridium catalysis in concert with N-aryl-phosphoramidite ligands. Broad functional group tolerance is observed at the keto-, ester-, and α-positions of the nucleophile. Various transformations demonstrating the utility of this method for rapidly accessing complex enantioenriched compounds are reported.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/42328, title ="Asymmetric Synthesis of QUINAP via Dynamic Kinetic Resolution", author = "Bhat, Vikram and Wang, Su", journal = "Journal of the American Chemical Society", volume = "135", number = "45", pages = "16829-16832", month = "November", year = "2013", doi = "10.1021/ja409383f", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20131108-073355250", note = "© 2013 American Chemical Society. \nPublished In Issue\nNovember 13, 2013.\nArticle ASAP\nNovember 04, 2013.\nJust Accepted Manuscript\nOctober 23, 2013.\nReceived: September 12, 2013.\nWe thank the Gordon and Betty Moore Foundation and Caltech\nfor financial support and Prof. Robert H. Grubbs, Prof. Sarah E.\nReisman, and Prof. Gregory C. Fu for helpful discussions. Dr.\nJacob Y. Cha, Mr. Andrew D. Lim, and Mr. Boram D. Hong are\nacknowledged for contributing samples of 2a and 2b.", revision_no = "29", abstract = "A palladium-catalyzed, atroposelective C−P coupling process has been developed for the asymmetric synthesis of QUINAP and its derivatives in high enantiomeric excess. Bromide, triflate (OTf) and 4-methanesulfonylbenzenesulfonate (OSs) precursors were studied, leading in the case of the triflate to a novel\ndynamic kinetic resolution involving isomerization of an arylpalladium intermediate. The operationally simple\nmethods described in this communication afford these important ligands in good to high yields and selectivity\nusing low catalyst loading (≤3 mol % Pd).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/42253, title ="Mechanism and Enantioselectivity in Palladium-Catalyzed Conjugate Addition of Arylboronic Acids to β‑Substituted Cyclic Enones: Insights from Computation and Experiment", author = "Holder, Jeffrey C. and Zou, Lufeng", journal = "Journal of the American Chemical Society", volume = "135", number = "40", pages = "14996-15007", month = "October", year = "2013", doi = "10.1021/ja401713g", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20131105-114622242", note = "© 2013 American Chemical Society. \n\nReceived: February 20, 2013. Publication Date (Web): September 12, 2013. \n\nThe authors thank NIH-NIGMS (B.M.S., R01 GM080269-01;\nK.N.H. GM36700), NSF (K.N.H., CHE-0548209), Caltech,\nAmgen, the American Chemical Society Division of Organic\nChemistry (predoctoral fellowship J.C.H.), the Swiss National\nScience Foundation (postdoctoral fellowship M.G.), and the\nJapan Society for the Promotion of Science (postdoctoral\nfellowship K.K.) for financial support. A.N.M. is grateful for a\nresearch fellowship by the German National Academy of\nSciences Leopoldina (LPDS 2011-12). Prof. Theodor Agapie\n(Caltech) is thanked for helpful discussions. Dr. David\nVanderVelde of the Caltech NMR facility is thanked for\ninvaluable assistance with NMR experiments and helpful\ndiscussions. Lawrence Henling and Dr. Michael K. Takase\n(Caltech) are gratefully acknowledged for X-ray crystallographic\nstructural determination. The Bruker KAPPA APEXII\nX-ray diffractometer was purchased via an NSF CRIF:MU\naward to the California Institute of Technology, CHE-0639094.\nThe Varian 400 MHz NMR spectrometer at Caltech was\npurchased via an NIH grant (RR027690). Calculations were\nperformed on the Hoffman2 cluster at UCLA and the Extreme\nScience and Engineering Discovery Environment (XSEDE),\nwhich is supported by the NSF. The authors declare no competing financial interest.", revision_no = "27", abstract = "Enantioselective conjugate additions of arylboronic acids to β-substituted cyclic enones have been previously reported from our laboratories. Air- and moisture-tolerant conditions were achieved with a catalyst derived in situ from palladium(II) trifluoroacetate and the chiral ligand (S)-t-BuPyOx. We now report a combined experimental and computational investigation on the mechanism, the nature of the active catalyst, the origins of the enantioselectivity, and the stereoelectronic effects of the ligand and the substrates of this transformation. Enantioselectivity is controlled primarily by steric repulsions between the t-Bu group of the chiral ligand and the α-methylene hydrogens of the enone substrate in the enantiodetermining carbopalladation step. Computations indicate that the reaction occurs via formation of a cationic arylpalladium(II) species, and subsequent carbopalladation of the enone olefin forms the key carbon–carbon bond. Studies of nonlinear effects and stoichiometric and catalytic reactions of isolated (PyOx)Pd(Ph)I complexes show that a monomeric arylpalladium–ligand complex is the active species in the selectivity-determining step. The addition of water and ammonium hexafluorophosphate synergistically increases the rate of the reaction, corroborating the hypothesis that a cationic palladium species is involved in the reaction pathway. These additives also allow the reaction to be performed at 40 °C and facilitate an expanded substrate scope.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/41655, title ="Use of a palladium(II)-catalyzed oxidative kinetic resolution in synthetic efforts toward bielschowskysin", author = "Meyer, Michael E. and Phillips, John H.", journal = "Tetrahedron", volume = "69", number = "36", pages = "7627-7635", month = "September", year = "2013", doi = "10.1016/j.tet.2013.02.034 ", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20131003-103642590", note = "© 2013 Elsevier Ltd. \n\nReceived 18 December 2012; Received in revised form 8 February 2013; Accepted 8 February 2013; Available online 19 February 2013. \n\nThe authors are grateful to the NIH-NIGMS (R01GM080269), the\nBristol-Myers Squibb Company (predoctoral fellowship to E.M.F.), California Institute of Technology, A. P. Sloan Foundation, the Dreyfus Foundation, Research Corporation, Abbott (d), Amgen, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Johnson and Johnson, Eli Lilly, Merck, Novartis, Pfizer, and Roche for generous funding.", revision_no = "17", abstract = "Progress toward the cyclobutane core of bielshowskysin is reported. The core was thought to arise from a cyclopropane intermediate via a furan-mediated cyclopropane fragmentation, followed by a 1,4-Michael addition. The synthesis of the cyclopropane intermediate utilizes a Suzuki coupling reaction, an esterification with 2-diazoacetoacetic acid, and a copper catalyzed cyclopropanation. An alcohol intermediate within the synthetic route was obtained in high enantiopurity via a highly selective palladium(II)-catalyzed oxidative kinetic resolution (OKR).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/41156, title ="A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx) ligand", author = "Shimizu, Hideki and Holder, Jeffrey C.", journal = "Beilstein Journal of Organic Chemistry", volume = "9", pages = "1637-1642", month = "August", year = "2013", doi = "10.3762/bjoc.9.187 ", issn = "1860-5397", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130906-155635457", note = "© 2013 Shimizu et al; licensee Beilstein-Institut.\n\nThis is an Open Access article under the terms of the\nCreative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which\npermits unrestricted use, distribution, and reproduction in\nany medium, provided the original work is properly cited.\n\nReceived: 06 June 2013;\nAccepted: 15 July 2013;\nPublished: 12 August 2013.\n\nThis publication is based on work supported by NIH-NIGMS\n(R01GM080269-01), and the authors additionally thank\nAmgen, Abbott, Boehringer Ingelheim, and Caltech for financial\nsupport. J.C.H. thanks the American Chemical Society\nDivision of Organic Chemistry for a graduate research fellowship.\nWe also thank Shionogi & Co., Ltd. for a research grant\nand fellowship to H.S.", revision_no = "16", abstract = "An efficient method for the synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx) ligand has been\ndeveloped. Inconsistent yields and tedious purification in known routes to (S)-t-BuPyOx suggested the need for an efficient,\ndependable, and scalable synthetic route. Furthermore, a route suitable for the synthesis of PyOx derivatives is desirable. Herein,\nwe describe the development of a three-step route from inexpensive and commercially available picolinic acid. This short procedure\nis amenable to multi-gram scale synthesis and provides the target ligand in 64% overall yield.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/41606, title ="Construction of Vicinal Tertiary and All-Carbon Quaternary Stereocenters via Ir-Catalyzed Regio-, Diastereo-, and Enantioselective Allylic Alkylation and Applications in Sequential Pd Catalysis", author = "Liu, Wen-Bo and Reeves, Corey M.", journal = "Journal of the American Chemical Society", volume = "135", number = "29", pages = "10626-10629", month = "July", year = "2013", doi = "10.1021/ja4052075 ", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20131002-102340513", note = "© 2013 American Chemical Society. \n\nReceived: May 23, 2013; Published: July 7, 2013. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. Shanghai Institute of Organic Chemistry (SIOC) is thanked for a postdoctoral fellowship to W.-B.L. Dr.\nMona Shahgholi and Naseem Torian are acknowledged for\nmass spectrometry assistance. Lawrence Henling is acknowledged for X-ray crystallographic structural determination. The authors thank Mr. Jeff Holder for the preparation of [Ir(cod)Cl]2. The authors are thankful to Professor Shu-Li You and Mr. Robert Craig for L3 and (R)-L8, respectively, and for helpful discussions.", revision_no = "22", abstract = "Highly congested vicinal stereocenters comprised of tertiary and all-carbon quaternary centers were generated via Ir-catalyzed asymmetric allylic alkylation of β-ketoesters. These catalytic reactions proceed in excellent yields with a broad scope on either reaction partner and with outstanding regio-, diastereo-, and enantiocontrol. Implementation of a subsequent Pd-catalyzed alkylation affords dialkylated products with pinpoint stereochemical control of both chiral centers.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/39741, title ="Development of a palladium-catalyzed decarboxylative cross-coupling of (2-azaaryl)carboxylates with aryl halides", author = "Haley, Christopher K. and Gilmore, Christopher D.", journal = "Tetrahedron", volume = "69", number = "27-28", pages = "5732-5736", month = "July", year = "2013", doi = "10.1016/j.tet.2013.03.085", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130802-141019170", note = "© 2013 Elsevier Ltd. \n\nReceived 6 February 2013. Received in revised form 15 March 2013. Accepted 19 March 2013. Available online 27 March 2013. \n\nDedicated to Professor Melanie Sanford on receipt of the Tetrahedron Young Investigator Award. The authors wish to thank NIH-NIGMS (R01 GM080269) for financial support.", revision_no = "18", abstract = "A catalytic method for the decarboxylative coupling of 2-(azaaryl)carboxylates with aryl halides is described. The decarboxylative cross-coupling presented is mediated by a system catalytic in both palladium and copper without requiring stoichiometric amounts of organometallic reagents or organoboronic acids. This method circumvents additional synthetic steps required to prepare 2-azaaryl organometallics and organoborates as nucleophilic coupling partners, which are prone to protodemetallation and protodeborylation and produce potentially toxic byproducts.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/39890, title ="Enantioselective Synthesis of the 5–6–7 Carbocyclic Core of the Gagunin Diterpenoids", author = "Shibuya, Grant M. and Enquist, John A., Jr.", journal = "Organic Letters", volume = "15", number = "13", pages = "3480-3483", month = "July", year = "2013", doi = "10.1021/ol401514s ", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130813-101335730", note = "© 2013 American Chemical Society. \n\nReceived May 29, 2013. Published on Web 06/26/2013. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269-01), Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. Mr. Austin Moehle (Caltech) is thanked for the preparation of early compounds. Dr. David Vander Velde (Caltech) is gratefully acknowledged for assistance with the characterization of compounds by NMR spectroscopy. Mr. Lawrence Henling (Caltech) is gratefully acknowledged for X-ray crystallographic structural determination and Dr. Alexander Goldberg (Caltech) is acknowledged for assisting in the preparation of crystallographic images for publication.\nMs. Kelly Kim (Caltech) is acknowledged for assistance\nwith the IR data of a late-stage compound. Materia, Inc.\nand Dr. Keith Keitz (Caltech) are thanked for the generous\ndonation of ruthenium catalysts. The Bruker KAPPA\nAPEXII X-ray diffractometer was purchased via an NSF\nCRIF:MU award to the California Institute of Technology,\nCHE-0639094. We also wish to acknowledge helpful\ndiscussions with Christina White (UIUC), Huw Davies\n(Emory), and other members of the CCI Center for Selective\nC-H Functionalization supported by NSF (CHE-1205646).", revision_no = "22", abstract = "A catalytic enantioselective double allylic alkylation reaction has been employed in the synthesis of the core of the gagunin diterpenoids. Enantioenriched material was advanced in 11 steps to afford the core of the highly oxygenated target, which includes two all-carbon quaternary stereocenters.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/41132, title ="Selective Nucleic Acid Capture with Shielded Covalent Probes", author = "Vieregg, Jeffrey R. and Nelson, Hosea M.", journal = "Journal of the American Chemical Society", volume = "135", number = "26", pages = "9691-9699", month = "July", year = "2013", doi = "10.1021/ja4009216 ", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130905-155148025", note = "© 2013 American Chemical Society. ACS AuthorChoice.\n\nReceived: January 27, 2013; Published: June 7, 2013. \n\nWe thank Dr. Peng Yin for discussions, Victoria Hsiao for\nperforming additional characterizations of photoreversal\nconditions, Dr. Joshua Day for synthesis of alternative\nphotocross-linkers, Dr. Le Trinh for providing plasmid\npCS2+mCherry:H2B and Maayan Schwarzkopf for providing\nplasmid pTNT-DsRed2. This work was funded by NIH\n5R01CA140759, NIH P50 HG004071, the Caltech Innovation\nInitiative, the Caltech Programmable Molecular Technology\nInitiative via Grant GBMF2809 from the Gordon and Betty\nMoore Foundation, an NSF Graduate Research Fellowship\n(H.M.N.), and a Ford Foundation Predoctoral Fellowship\n(H.M.N.).", revision_no = "14", abstract = "Nucleic acid probes are used for diverse applications in vitro, in situ, and in vivo. In any setting, their power is limited by imperfect selectivity (binding of undesired targets) and incomplete affinity (binding is reversible, and not all desired targets bound). These difficulties are fundamental, stemming from reliance on base pairing to provide both selectivity and affinity. Shielded covalent (SC) probes eliminate the longstanding trade-off between selectivity and durable target capture, achieving selectivity via programmable base pairing and molecular conformation change, and durable target capture via activatable covalent cross-linking. In pure and mixed samples, SC probes covalently capture complementary DNA or RNA oligo targets and reject two-nucleotide mismatched targets with near-quantitative yields at room temperature, achieving discrimination ratios of 2–3 orders of magnitude. Semiquantitative studies with full-length mRNA targets demonstrate selective covalent capture comparable to that for RNA oligo targets. Single-nucleotide DNA or RNA mismatches, including nearly isoenergetic RNA wobble pairs, can be efficiently rejected with discrimination ratios of 1–2 orders of magnitude. Covalent capture yields appear consistent with the thermodynamics of probe/target hybridization, facilitating rational probe design. If desired, cross-links can be reversed to release the target after capture. In contrast to existing probe chemistries, SC probes achieve the high sequence selectivity of a structured probe, yet durably retain their targets even under denaturing conditions. This previously incompatible combination of properties suggests diverse applications based on selective and stable binding of nucleic acid targets under conditions where base-pairing is disrupted (e.g., by stringent washes in vitro or in situ, or by enzymes in vivo).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/39845, title ="Enantioselective Construction of α-Quaternary Cyclobutanones by Catalytic Asymmetric Allylic Alkylation", author = "Reeves, Corey M. and Eidamshaus, Christian", journal = "Angewandte Chemie International Edition", volume = "52", number = "26", pages = "6718-6721", month = "June", year = "2013", doi = "10.1002/anie.201301815 ", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130809-133957166", note = "© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.\n\nReceived: March 4, 2013; Revised: April 17, 2013; Published online: May 17, 2013.\n\nThe authors wish to thank NIH-NIGMS (R01GM080269-01),\nDeutsche Forschungsgemeinschaft (DFG postdoctoral fellowship\nto C.E.), Amgen, Abbott, Boehringer Ingelheim, and Caltech for\nfinancial support. Materia, Inc. is gratefully acknowledged for the\ndonation of catalysts. Dr. Mona Shahgholi and Naseem Torian are\nacknowledged for high-resolution mass spectrometry assistance.\nJonny Gordon is acknowledged for insightful discussions. Robert\nCraig is gratefully acknowledged for providing compound L3 and for\ninsightful discussion.", revision_no = "27", abstract = "No strain, no gain! The first transition metal-catalyzed enantioselective α-alkylation of cyclobutanones is reported. This method employs palladium catalysis and an electron-deficient PHOX-type ligand to afford all-carbon α-quaternary cyclobutanones in good to excellent yields and enantioselectivities (see scheme).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/39844, title ="Total Syntheses of (-)-Transtaganolide A, (+)-Transtaganolide B, (+)-Transtaganolide C, and (-)-Transtaganolide D and Biosynthetic Implications", author = "Nelson, Hosea M. and Gordon, Jonny R.", journal = "Angewandte Chemie International Edition", volume = "52", number = "26", pages = "6699-6703", month = "June", year = "2013", doi = "10.1002/anie.201301212 ", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130809-132636851", note = "© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.\n\nReceived: February 11, 2013;\nPublished online: May 16, 2013.\n\nThe authors wish to thank the NSF and Ford Foundation\n(predoctoral fellowships to H.M.N.), Amgen, Abbott, Boehringer\nIngelheim, the Gordon and Betty Moore Foundation, and Caltech\nfor financial support. Prof. Giovanni Appendino is acknowledged for\nproviding authentic samples of basiliolide B. Dr. Kei Murakami is\nacknowledged for his contribution to the preparation of racemic\ntranstaganolides C and D. Kelly Kim and Alexander Goldberg are\ngratefully acknowledged for assistance in manuscript preparation.\nDr. Nolan McDougal is acknowledged for useful discussions\nregarding biosynthesis. Larry Henling is acknowledged for X-ray\nanalysis of 33. Dr. David VanderVelde is acknowledged for NMR\nassistance. The authors wish to thank NIH-NIGMS\n(R01GM080269) for financial support. The Bruker KAPPA APEXII Xray\ndiffractometer used in this study was purchased through an NSF\nCRIF:MU award to Caltech (CHE-0639094).", revision_no = "28", abstract = "‘Dibal'lin’ on a budget: The enantioselective total syntheses of transtaganolides\u2005A–D are rapidly achieved by a highly diastereoselective Ireland–Claisen/Diels–Alder cascade reaction of an enantioenriched geraniol derivative (see scheme). Based on X-ray diffraction data, the absolute configuration of these metabolites is established and discussed within the context of existing biosynthetic hypotheses.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/39005, title ="The Construction of All-Carbon Quaternary Stereocenters by Use of Pd-Catalyzed Asymmetric Allylic Alkylation Reactions in Total Synthesis", author = "Hong, Allen Y. and Stoltz, Brian M.", journal = "European Journal of Organic Chemistry", volume = "2013", number = "14", pages = "2745-2759", month = "May", year = "2013", doi = "10.1002/ejoc.201201761 ", issn = "1434-193X", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130620-142930731", note = "© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nReceived: December 30, 2012; Published Online: March 27, 2013. \n\nThe authors thank National Institutes of Health – National Institute\nof General Medical Sciences (grant number R01GM080269-\n01), Roche, Abbott Laboratories, Amgen, Boehringer Ingelheim,\nthe Gordon and Betty Moore Foundation, and Caltech for awards\nand financial support. Nick O’Connor, Kelly Kim, and Christopher\nHaley are acknowledged for editorial assistance.\n", revision_no = "17", abstract = "All-carbon quaternary stereocenters have posed significant challenges in the synthesis of complex natural products. These important structural motifs have inspired the development of broadly applicable palladium-catalyzed asymmetric allylic alkylation reactions of unstabilized non-biased enolates for the synthesis of enantioenriched α-quaternary products. This microreview outlines key considerations in the application of palladium-catalyzed asymmetric allylic alkylation reactions and presents recent total syntheses of complex natural products that have employed these powerful transformations for the direct, catalytic, enantioselective construction of all-carbon quaternary stereocenters.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/37870, title ="Development of a palladium-catalyzed enantioselective conjugate addition of arylboronic acids to cyclic conjugate acceptors", author = "Holder, Jeffrey C. and Kikushima, Kotaro", pages = "ORGN 786", month = "April", year = "2013", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130410-144615697", note = "© 2013 American Chemical Society.", revision_no = "13", abstract = "The first enantioselective Pd-catalyzed construction of all-carbon quaternary stereocenters\nvia 1,4-addn. of arylboronic acids to β-substituted cyclic enones is reported. Reaction of a\nwide range of arylboronic acids and cyclic enones using a catalyst prepd. from Pd(OCOCF_3)_2 and a chiral pyridinooxazoline ligand yields enantioenriched products bearing benzylic\nstereocenters. Notably, this transformation is tolerant to air and moisture, providing a\npractical and operationally simple method of synthesizing enantioenriched all-carbon\nquaternary stereocenters.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/38193, title ="Expanding Insight into Asymmetric Palladium-Catalyzed Allylic Alkylation of N-Heterocyclic Molecules and Cyclic Ketones", author = "Bennett, Nathan B. and Duquette, Douglas C.", journal = "Chemistry: a European Journal", volume = "19", number = "14", pages = "4414-4418", month = "April", year = "2013", doi = "10.1002/chem.201300030", issn = "0947-6539", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130501-072844784", note = "© 2013 Wiley-VCH Verlag GmbH & Co. Issue published online: 20 Mar 2013. Article first published online: 27 Feb 2013. Manuscript Received: 12 Nov 2012. The authors thank NIH-NIGMS (R01 M080269-01), Roche, Abbott Laboratories,\nAmgen, Boehringer Ingelheim, the Gordon and Betty Moore\nFoundation, and Caltech for awards and financial support. D.C.D. thanks the National Science Foundation for financial support (Predoctoral Research Fellowship, No. DGE-1144469). W.-B.L. thanks the Shanghai Institute of Organic Chemistry for financial support (SIOC Postdoctoral Fellowship). A.N.M. is grateful for a fellowship by the Deutsche Akademie\nder Naturforscher Leopoldina. Profs. Sarah Reisman and Theodor Agapie are acknowledged for helpful discussions and suggestions. Dr. David VanderVelde and Dr. Scott Ross are acknowledged for NMR assistance. Dr. Mona Shahgoli and Naseem Torian are acknowledged for High-Resolution Mass Spectrometry assistance.", revision_no = "30", abstract = "Eeny, meeny, miny … enaminones! Lactams and imides have been shown to consistently provide enantioselectivities substantially higher than other substrate classes previously investigated in the palladium-catalyzed asymmetric decarboxylative allylic alkylation. Several new substrates have been designed to probe the contributions of electronic, steric, and stereoelectronic factors that distinguish the lactam/imide series as superior alkylation substrates (see scheme). These studies culminated in marked improvements on carbocyclic allylic alkylation substrates.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/38195, title ="Frequency Locked Microtoroid Optical Resonators as a Non-Invasive Tumor Biopsy Alternative", author = "Su, Judith and Goldberg, Alex", journal = "Biophysical Journal", volume = "104", number = "2", pages = "528A", month = "January", year = "2013", doi = "10.1016/j.bpj.2012.11.2924", issn = "0006-3495", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130501-082658216", note = "© 2013 Biophysical Society. Published by Elsevier Inc. ", revision_no = "12", abstract = "Whispering gallery mode optical resonators offer an unusual coupling of rapid response time and ultra-sensitive biological and chemical detection. We have improved the signal to noise ratio of microtoroid optical resonators ∼1000-fold over standard techniques by using laser frequency locking and have applied this to assay tumor progression in mice by sensing the low concentrations of exosomes, shed by tumor cells, in serum samples collected from the animals. Serum samples from normal or experimental mice cause no shift in the resonance wavelength of the microtoroids; however, after using antibodies toward specific tumor markers to sensitize the toroid surface, we detected changes in the resonance frequency of the microtoroid when exposed to the serum of tumor-implanted mice. Serum from control (tumor-free) mice caused no shift. The wavelength shifts observed were 600 times the noise and drift of the sensor, even for a million fold dilution of the serum sample. Analysis of the shifts showed unitary steps of ∼ 0.5 fm, suggesting that the assay may be sensitive enough to detect individual binding events, offering a means to analyze the size of the biomolecules that are binding to the resonator. If validated, this approach offers a non-invasive tumor “biopsy,” exploiting the circulation of blood to collect a sample of tumor surfaces without the need to find or access the tumors.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/36880, title ="Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Heterocyclic Acceptors", author = "Holder, Jeffrey C. and Marziale, Alexander N.", journal = "Chemistry: a European Journal", volume = "19", number = "1", pages = "74-77", month = "January", year = "2013", doi = "10.1002/chem.201203643", issn = "0947-6539", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130212-115138312", note = "© 2013 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim. \n\nReceived: September 19, 2012; Published online: December 3, 2012. \n\nThe authors thank NIH-NIGMS (R01M080269–01), Caltech, Amgen, and the Deutsche Akademie der Naturforscher Leopoldina (postdoctoral fellowship A.N.M.) for financial support. J. C. H. thanks the American Chemical Society Division of Organic Chemistry for a predoctoral fellowship. M.G. is grateful to the Swiss National Science Foundation for financial support through a postdoctoral fellowship. B. M. thanks the China Scholarship Council (No.2008618001) and the University of Groningen for financial support. Anton A. Toutov is acknowledged for experimental assistance. Jinglan Zhou and Mike DeNinno (Vertex Pharmaceuticals) are acknowledged for helpful discussions and suggestions.", revision_no = "21", abstract = "Flava Flavanone: Asymmetric conjugate additions to chromones and 4-quinolones are reported utilizing a single catalyst system formed in situ from Pd(OCOCF_3)_2 and (S)-tBuPyOX. Notably, these reactions are performed in wet solvent under ambient atmosphere, and employ readily available arylboronic acids as the nucleophile, thus providing ready access to these asymmetric heterocycles.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/37404, title ="Rapid and Convergent Synthesis of a 2,4’-Linked Tri-oxazole in an Approach to Poly-oxazoles", author = "Caspi, Daniel D. and Zhang, Haiming", journal = "Heterocycles", volume = "86", number = "2", pages = "1003-1008", month = "December", year = "2012", doi = "10.3987/COM-12-S(N)118", issn = "0385-5414", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130308-082047917", note = "© 2012 The Japan Institute of Heterocyclic Chemistry.\n\nReceived, 3rd September, 2012; Accepted, 22nd October, 2012; Published online, 12th November, 2012.\n\nDedicated to Professor Ei-ichi Negishi on the occasion of his 77th birthday.\n\nThe authors gratefully acknowledge the NIH-NIGMS (R01 GM65961-01), Eli Lilly (predoctoral\nfellowship to D.D.C.), AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Pfizer, Merck, Amgen,\nResearch Corporation, Roche, and GlaxoSmithKline for generous funding. We also thank Tim Dong and\nJ. T. Mohr for experimental assistance.", revision_no = "14", abstract = "A rapid and convergent synthesis of a 2,4’-linked tri-oxazole using a Negishi coupling is described.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/36359, title ="The Reaction Mechanism of the Enantioselective Tsuji Allylation: Inner-Sphere and Outer-Sphere Pathways, Internal Rearrangements, and Asymmetric C–C Bond Formation", author = "Keith, John A. and Behenna, Douglas C.", journal = "Journal of the American Chemical Society", volume = "134", number = "46", pages = "19050-19060", month = "November", year = "2012", doi = "10.1021/ja306860n", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130114-141639858", note = "© 2012 American Chemical Society.\n\nReceived: July 19, 2012; published: October 28, 2012.\n\nWe thank K. Tani, A. Harned, and J. Enquist for experimental\ncollaboration and discussion, and M. Day and L. Henling for\ncrystallography assistance. J.A.K. thanks A. Tkatchenko for\ndiscussions and calculations with dispersion-corrected DFT.\nThis research was partly funded by Chevron-Texaco, and the\nfacilities used were funded by grants from ARO−DURIP,\nONR-DURIP, IBM-SUR, Fannie and John Hertz Foundation\n(D.C.B.), and Eli Lilly (J.T.M.) with additional support from NSF (CTS-0608889 and CHE-1214158, W.A.G.) and NIHNIGMS\n(R01GM080269-01, B.M.S.).", revision_no = "25", abstract = "We use first principles quantum mechanics (density functional theory) to report a detailed reaction mechanism of the asymmetric Tsuji allylation involving prochiral nucleophiles and nonprochiral allyl fragments, which is consistent with experimental findings. The observed enantioselectivity is best explained with an inner-sphere mechanism involving the formation of a 5-coordinate Pd species that undergoes a ligand rearrangement, which is selective with regard to the prochiral faces of the intermediate enolate. Subsequent reductive elimination generates the product and a Pd^0 complex. The reductive elimination occurs via an unconventional seven-centered transition state that contrasts dramatically with the standard three-centered C–C reductive elimination mechanism. Although limitations in the present theory prevent the conclusive identification of the enantioselective step, we note that three different computational schemes using different levels of theory all find that inner-sphere pathways are lower in energy than outer-sphere pathways. This result qualitatively contrasts with established allylation reaction mechanisms involving prochiral nucleophiles and prochiral allyl fragments. Energetic profiles of all reaction pathways are presented in detail.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/36201, title ="Enantioselective Synthesis of a Hydroxymethyl-cis-1,3-cyclopentenediol Building Block", author = "Craig, Robert A., II and Roizen, Jennifer L.", journal = "Organic Letters", volume = "14", number = "22", pages = "5716-5719", month = "November", year = "2012", doi = "10.1021/ol3027297", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130107-104400691", note = "© 2012 American Chemical Society. \n\nReceived October 2, 2012. Publication Date (Web): October 26, 2012. \nThe authors wish to thank NIH-NIGMS (R01GM080269-01), NIH Grant F32GM082000 (postdoctoral fellowship to A.C.J.), the California Tobacco-Related Disease Research Program of the University of California, Grant Number 14DT-0004 (predoctoral fellowship to J.L.R.), Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. Dr. Nathaniel Sherden, Dr. Masaki Seto, Dr. Pamela Tadross, Dr. Scott Virgil, Mr. Jeffery Holder, Mr. Corey Reeves, and Ms. Amanda Silberstein (Caltech) are thanked for helpful discussions and experimental support.", revision_no = "24", abstract = "A brief, enantioselective synthesis of a hydroxymethyl-cis-1,3-cyclopentenediol building block is presented. This scaffold allows access to the cis-1,3-cyclopentanediol fragments found in a variety of biologically active natural and non-natural products. This rapid and efficient synthesis is highlighted by the utilization of the palladium-catalyzed enantioselective allylic alkylation of dioxanone substrates to prepare tertiary alcohols.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/37952, title ="Catalytic Enantioselective Alkylation of Prochiral Ketone Enolates", author = "Reeves, Corey M. and Stoltz, Brian M.", pages = "1-10", month = "November", year = "2012", doi = "10.1002/9783527652235.ch1", isbn = "9783527329212", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130415-152954275", note = "© 2012 Wiley-VCH Verlag GmbH & Co. KGaA.\nPublished 2012 by Wiley-VCH Verlag GmbH & Co. KGaA.\n\nPublished Online: 14 Jan 2013; Published Print: 14 Nov 2012", revision_no = "17", abstract = "The synthesis of stereogenic all-carbon quaternary centers remains a formidable\nchallenge, notwithstanding the strides made by modem organic chemistry in this\nregard. Contemporary advances in enolate alkylation have made it a fundamental\nstrategy for the construction of C-C bonds. Although methods for the reaction\nof a number of enolate types (e.g., ester, ketone, and propionimide) with a variety of\nalkylating agents exist, catalytic enantioselective variants of these transformations\nare relatively rare. Of the catalytic asymmetric methods available, there have been\nfew examples of general techniques for the asymmetric alkylation of carbocyclic\nsystems and still fewer examples that have the capacity to deliver all-carbon\nquaternary stereocenters. While the Merck phase transfer methylation and Koga\nalkylation of 2-alkyltetralone-derived silyl enol ethers represent notable exceptions, the breadth of application and utility of these reactions bas been limited. In fact,\nat the outset of our investigations in this area, there were no examples of catalytic\nenantioselective alkylations of monocyclic 2-substituted cycloalkanone enolates in\nthe absence of either α'-blocking groups or α-enolate-stabilizing groups (e.g., R =\naryl, ester, etc.; Figure 1). Concurrent to our work in this area, Trost and coworkers have published a series of papers that complement our studies. Jacobsen and\ncoworkers, as well, have revealed a unique enantioselective method involving the\nchromium-catalyzed reaction of tin enolates with a variety of unactivated alkyl\nhalides . Herein, we relate our development of Pd-catalyzed enantioselective\nfunctionalization reactions of prochiral enolates, specifically tetrasubstituted cyclic\nketone enolates that give rise to quaternary stereogenicity. The synthetic utility\nof the building blocks derived from these reactions is demonstrated by application\nin a number of total syntheses.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/35762, title ="Lewis Acid Mediated (3 + 2) Cycloadditions of Donor–Acceptor Cyclopropanes with Heterocumulenes", author = "Goldberg, Alexander F. G. and O’Connor, Nicholas R.", journal = "Organic Letters", volume = "14", number = "20", pages = "5314-5317", month = "October", year = "2012", doi = "10.1021/ol302494n ", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20121203-103554504", note = "© 2012 American Chemical Society. \n\nPublication Date (Web): October 9, 2012. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269-01), Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. A.G. gratefully acknowledges the Natural Sciences and Engineering Research Council (NSERC) of Canada for a PGS D scholarship. Dr. Michael R. Krout (Bucknell University) and Jonathan R. Gordon (Caltech) are thanked for helpful discussions. Lawrence Henling (Caltech) is gratefully acknowledged for X-ray crystallographic structural determination. The Bruker KAPPA APEXII X-ray diffractometer\nwas purchased via an NSF CRIF:MU award to the California\nInstitute of Technology, CHE-0639094. The Varian\n400 MHz NMR spectrometer was purchased via an NIH\ngrant (RR027690).", revision_no = "40", abstract = "Isocyanates, isothiocyanates, and carbodiimides are effective substrates in (3 + 2) cycloadditions with donor–acceptor cyclopropanes for the synthesis of five-membered heterocycles. These reactions exhibit a broad substrate scope, high yields, and well-defined chemoselectivity. Discussed herein are the implications of Lewis acid choice on the stereochemical outcome and the reaction mechanism.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/52975, title ="Enantioselective Total Synthesis of the Reported Structures of (−)-9-epi-Presilphiperfolan-1-ol and (−)-Presilphiperfolan-1-ol: Structural Confirmation and Reassignment and Biosynthetic Insights", author = "Hong, Allen Y. and Stoltz, Brian M.", journal = "Angewandte Chemie International Edition", volume = "51", number = "38", pages = "9674-9678", month = "September", year = "2012", doi = "10.1002/anie.201205276", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141217-142148376", note = "Copyright © 2012 WILEY-VCH. \n\nReceived: July 4, 2012. Published online: August 22, 2012. \n\nIn memory of Michael W. Day. \n\nThe authors thank NIH-NIGMS (R01GM080269-01), Roche, Abbott Laboratories, Amgen, Boehringer Ingelheim, the Gordon and Betty Moore Foundation, and Caltech for awards and financial support. Prof. Suzana\u2005G. Leitão (Universidade Federale do Rio de Janeiro) generously provided NMR spectra for natural 2. Dr. Lawrence Henling is gratefully acknowledged for X-ray crystallographic structure determination. The Bruker KAPPA APEXII X-ray diffractometer used in this study was purchased through an NSF CRIF:MU award to Caltech (CHE-0639094). Prof. Sarah Reisman, Dr. Scott Virgil, Dr. Douglas\u2005C. Behenna, Robert J. Ely and Fang Gao (Boston College), and Jessica Y. Wu (Harvard University) are acknowledged for helpful discussions and suggestions. Dr. David VanderVelde and Dr. Scott Ross are acknowledged for NMR assistance.", revision_no = "25", abstract = "The first total synthesis of the reported structures of 9-epi-presilphiperfolan-1-ol and presilphiperfolan-1-ol has been achieved. Key steps are a catalytic asymmetric alkylation of a novel diene-containing electrophile followed by a two-carbon ring contraction and an intramolecular Diels–Alder cycloaddition to form the stereochemically dense tricyclic core. The synthetic work has resulted in the structural revision of presilphiperfolan-1-ol (see scheme).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/35160, title ="A C–N insertion of β-lactam to benzyne: unusual formation of acridone", author = "Kim, Jimin and Stoltz, Brian M.", journal = "Tetrahedron Letters", volume = "53", number = "37", pages = "4994-4996", month = "September", year = "2012", doi = "10.1016/j.tetlet.2012.07.026 ", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20121029-133109161", note = "© 2012 Elsevier Ltd. \n\nReceived 29 June 2012. Revised 4 July 2012. Accepted 6 July 2012. Available online 16 July 2012. \n\nThe authors acknowledge Abbott, Amgen, Boehringer Ingelheim,\nthe Teva USA Scholars Program, and Caltech for financial\nsupport. We also thank Dr. Pamela Tadross and Mr. Christopher\nHaley for helpful discussions and materials.", revision_no = "12", abstract = "Intermolecular insertion of benzyne into the C–N bond of a β-lactam is described. This σ-insertion is followed by ring expansion that produces dihydroquinolinone, which rapidly reacts with an additional benzyne unit to afford an acridone through intramolecular C–C bond formation to the carbonyl group and rapid elimination of ethylene.", } @book_section {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/38547, title ="Natural Products as Inspiration for Reaction Development: Catalytic Enantioselective Decarboxylative Reactions of Prochiral Enolate Equivalents", author = "Behenna, Douglas C. and Stoltz, Brian M.", number = "44", pages = "281-314", month = "August", year = "2012", doi = "10.1007/3418_2012_49", isbn = "978-3-642-34285-1", url = "https://resolver.caltech.edu/CaltechAUTHORS:20130516-140126410", note = "© 2013 Springer-Verlag Berlin Heidelberg.\n\nPublished online: 18 August 2012.\n", revision_no = "19", abstract = "This account describes the circumstances leading to our group's\ninnovations in the area of decarboxylative asymmetric allylic alkylation reactions\nand the initial discovery of palladium phosphinooxazoline complexes as efficient\nenantioselective catalysts. This chapter also chronicles the growth of the methodology\nto include several substrate classes, the expansion of the project into several other\nreaction manifolds, and the use of these reactions in natural product synthesis. Finally,\nimportant contributions from other research groups involving related methods or\nproducts similar to the α-quaternary products that are the focus of our studies, as\nwell as future directions for asymmetric alkylation reactions, are discussed.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/33438, title ="Novel approach to antitumor antibiotics: Using the power of benzyne in synthesis", author = "Stoltz, Brian M.", pages = "G+A-1", month = "August", year = "2012", url = "https://resolver.caltech.edu/CaltechAUTHORS:20120822-092222870", revision_no = "12", abstract = "We have initiated a research program directed toward the tetrahydroisoquinoline (THIQ) antitumor antibiotics, a class of bioactive alkaloids with existing clin. applications. Central to our approach is the development of new aryne annulation methods for the synthesis of isoquinolines. Our initial application of this method in a THIQ synthesis was to a concise asym. total synthesis of (-)-quinocarcin. Our current work in the area will be discussed.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/33463, title ="Sensitive and selective nucleic acid capture with shielded covalent probes", author = "Vieregg, Jeffrey R. and Nelson, Hosea", pages = "BIOL-218", month = "August", year = "2012", url = "https://resolver.caltech.edu/CaltechAUTHORS:20120822-154455462", revision_no = "12", abstract = "Nucleic acid probes are used for diverse applications in vitro, in situ, and in vivo. In any setting, their power is limited by imperfect selectivity (binding of undesired targets) and incomplete affinity (binding is reversible and not all desired targets are bound). These limitations stem from reliance on base pairing to both reject off-targets and retain desired targets. To address this selectivity/affinity tradeoff, shielded covalent probes achieve selectivity via conformation change and durable capture via covalent crosslinking of a photoactive nucleoside analog. In vitro assays show that mismatches are efficiently rejected and desired targets are durably captured. For probes designed to reject two-nucleotide mismatches, desired targets are captured nearly quant. Single-nucleotide mismatches are discriminated near the thermodn. limit. The probes operate isothermally and crosslinking activation is rapid with low-cost light sources. If desired, crosslinks can be reversed to release the target after capture. We envision a wide array of applications.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/32375, title ="A Comprehensive History of Arynes in Natural Product Total\nSynthesis", author = "Tadross, Pamela M. and Stoltz, Brian M.", journal = "Chemical Reviews", volume = "112", number = "6", pages = "3550-3577", month = "June", year = "2012", doi = "10.1021/cr200478h", issn = "0009-2665", url = "https://resolver.caltech.edu/CaltechAUTHORS:20120712-093347151", note = "© 2012 American Chemical Society. \n\nReceived: December 22, 2011; Published: March 23, 2012. \n\nThe authors thank Abbott, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Sigma−Aldrich, Teva, and Caltech for financial support and Dr. Kevin Allan, Dr. Kun-Liang (Phil) Wu, and Mr. Christopher Haley for editorial assistance.", revision_no = "25", abstract = "Within 14 years of the seminal experiments of J. D. Roberts\nleading to the first proposal of the structure of benzyne (1), synthetic organic chemists recognized the potential to exploit this highly reactive intermediate (and its substituted variants) in the total synthesis of natural products. More specifically, it was recognized that arynes offered the strategic advantage of rapidly functionalizing an aromatic ring by forming multiple carbon− carbon or carbon−heteroatom bonds in a single operation, often in a regioselective manner. Initially, the scope of synthetic\napplications was somewhat limited by the harsh conditions\nrequired to produce the aryne species. Many of these methods required strong bases, such as n-BuLi, or high temperatures (Scheme 1). However, with the development of milder methods for the generation of arynes came increased interest in employing them in the synthesis of more complex polycyclic systems. Most recently, the use of o-silyl aryl triflates as aryne precursors has allowed generation of the reactive intermediate under almost neutral conditions.\nTo date, over 75 individual natural products have been\nprepared using arynes to generate key synthetic intermediates. Herein are recounted the reports of total syntheses that utilize arynes in ways that build complexity or introduce motifs essential to the completion of their targets. The methods by which the authors featured in this review accomplish this task reflect the versatility of arynes as reactive intermediates for synthesis (Scheme 2). For the purposes of organization, the syntheses are divided into subgroups on the basis of the type of aryne transformation: (i) nucleophilic additions or multicomponent reactions, (ii) σ-bond insertion reactions, (iii) [4 + 2]- and [2 + 2]-cycloaddition strategies, and (iv) metal-catalyzed aryne reactions.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/28980, title ="Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams", author = "Behenna, Douglas C. and Liu, Yiyang", journal = "Nature Chemistry", volume = "4", number = "2", pages = "130-133", month = "February", year = "2012", doi = "10.1038/nchem.1222", issn = "1755-4330", url = "https://resolver.caltech.edu/CaltechAUTHORS:20120126-101327960", note = "© 2012 Macmillan Publishers Limited. \n\nReceived 13 October 2011; Accepted 07 November 2011; Published online 18 December 2011. \n\nThis publication is based on work supported by award from the King Abdullah University of Science and Technology (KAUST; no. KUS-11-006-02). The authors thank NIH-NIGMS (R01GM080269-01 and a postdoctoral fellowship to D.E.W.), the Gordon and Betty Moore Foundation, Amgen, Abbott, Boehringer Ingelheim and Caltech for financial support. T.Y. acknowledges the Japan Society for the Promotion of Science for a predoctoral fellowship. \n\nAuthor contributions: D.C.B., Y.L., T.Y. and J.K. planned and carried out the experimental work. D.C.B., T.Y., D.E.W. and S.C.V. took part in the initial reaction development and screening experiments. B.M.S. conceived, initiated and directed the project and wrote the manuscript. All authors commented on the manuscript.", revision_no = "26", abstract = "The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/27359, title ="Synthesis of enantioenriched γ-quaternary cycloheptenones using a combined allylic alkylation/Stork–Danheiser approach: preparation of mono-, bi-, and tricyclic systems", author = "Bennett, Nathan B. and Hong, Allen Y.", journal = "Organic and Biomolecular Chemistry", volume = "10", number = "1", pages = "56-59", month = "January", year = "2012", doi = "10.1039/C1OB06189E", issn = "1477-0520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20111021-144400118", note = "© 2011 The Royal Society of Chemistry. Received 17 Jul 2011, Accepted 27 Aug 2011. First published on the web 01 Sep 2011. This publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). The authors wish to thank NIH-NIGMS (R01GM080269-01), Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. AMH thanks the NIH for a postdoctoral fellowship. Materia, Inc. is gratefully acknowledged for the donation of catalysts. Michael Krout, Thomas Jensen, Christopher Henry, Scott Virgil, and Sarah Reisman are acknowledged for helpful discussions. David VanderVelde is acknowledged for critical NMR support.", revision_no = "24", abstract = "A general method for the synthesis of β-substituted and unsubstituted cycloheptenones bearing enantioenriched all-carbon γ-quaternary stereocenters is reported. Hydride or organometallic addition to a seven-membered ring vinylogous ester followed by finely tuned quenching parameters achieves elimination to the corresponding cycloheptenone. The resulting enones are elaborated to bi- and tricyclic compounds with potential for the preparation of non-natural analogs and whose structures are embedded in a number of cycloheptanoid natural products.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/28938, title ="Palladium-catalyzed asymmetric alkylation in the synthesis of cyclopentanoid and cycloheptanoid core structures bearing all-carbon quaternary stereocenters", author = "Hong, Allen Y. and Bennett, Nathan B.", journal = "Tetrahedron", volume = "67", number = "52", pages = "10234-10248", month = "December", year = "2011", doi = "10.1016/j.tet.2011.10.031", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20120124-111234894", note = "© 2011 Elsevier Ltd. Received 7 September 2011. Received in revised form 7 October 2011. Accepted 10 October 2011. Available online 19 October 2011. This publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). The authors wish to thank NIH-NIGMS (R01M080269-01), Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. A.Y.H. thanks Roche for an Excellence in Chemistry Award and Abbott for an Abbott Scholars Symposium Award. M.R.K. acknowledges Eli Lilly for a predoctoral fellowship.\nT.J. thanks the Danish Council for Independent Research/Natural Sciences for a postdoctoral fellowship. Materia, Inc. is gratefully acknowledged for the donation of metathesis catalysts. Lawrence Henling and Dr. Michael Day are acknowledged for X-ray crystallographic structure determination. The Bruker KAPPA APEXII X-ray diffractometer used in this study was purchased via an NSF CRIF:MU award to Caltech (CHE-0639094). Prof. Sarah Reisman, Dr. Scott Virgil, Dr. Christopher Henry, and Dr. Nathaniel Sherden\ncontributed with helpful discussions. Dr. David VanderVelde and Dr. Scott Ross are acknowledged for NMR assistance. The Varian 400 MR instrument used in this study was purchased via an NIH award to Caltech (NIH RR027690). Dr. Mona Shahgholi and Naseem Torian are acknowledged for high-resolution mass spectrometry assistance.", revision_no = "41", abstract = "General catalytic asymmetric routes toward cyclopentanoid and cycloheptanoid core structures embedded in numerous natural products have been developed. The central stereoselective transformation in our divergent strategies is the enantioselective decarboxylative alkylation of seven-membered β-ketoesters to form α-quaternary vinylogous esters. Recognition of the unusual reactivity of β-hydroxyketones resulting from the addition of hydride or organometallic reagents enabled divergent access to\ny-quaternary acylcyclopentenes through a ring contraction pathway or y-quaternary cycloheptenones through a carbonyl transposition pathway. Synthetic applications of these compounds were explored through the preparation of mono-, bi-, and tricyclic derivatives that can serve as valuable intermediates for the total synthesis of complex natural products. This work complements our previous work with\ncyclohexanoid systems.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/29280, title ="Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies", author = "Behenna, Douglas C. and Mohr, Justin T.", journal = "Chemistry: a European Journal", volume = "17", number = "50", pages = "14199-14223", month = "December", year = "2011", doi = "10.1002/chem.201003383", issn = "0947-6539", url = "https://resolver.caltech.edu/CaltechAUTHORS:20120214-111558996", note = "© 2011 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.\n\nReceived: November 24, 2010; Revised: July 29, 2011; Published online: November 14, 2011.\n\nThis publication is based on work supported by award number KUS-11–006–02, made by the King Abdullah University of Science and Technology (KAUST). We thank the NIH-NIGMS (R01 GM080269–01 and postdoctoral fellowships to AMH and DEW), The Fannie and John Hertz Foundation (predoctoral fellowship to DCB), Eli Lilly (predoctoral fellowships to JTM, RMM, and MRK), Ono Pharmaceutical Co., Ltd.\n(postdoctoral fellowship to KT), The Hungarian–American Enterprise Scholarship Fund (postdoctoral fellowship to ZN), Takeda Pharmaceutical Co., Ltd. (postdoctoral fellowship to MS), The California Tobacco-Related Disease Research Program of the University of California (predoctoral fellowship to JLR, grant number 14DT-0004), Marcella R. Bonsall and the Dalton Fund (undergraduate fellowships to SRL), the Caltech Amgen Scholars Program (undergraduate fellowship to KVP), The 21st Century COE Program for Frontiers in Fundamental Chemistry from the Ministry of Education, Culture, Sports, Science and Technology, Japan (financial support to AI), the A. P. Sloan Foundation, Research Corporation, the Dreyfus Foundation, Bristol–Myers Squibb, Glaxo-SmithKline, Johnson and Johnson, Amgen, Merck Research Laboratories, Pfizer, Novartis, Roche, Abbott Laboratories, Boehringer–Ingelheim,\nAstraZeneca, and Caltech for financial support. We acknowledge Dr. Mike Day and Larry Henling for assistance with X-ray crystallography. Ruthenium olefin metathesis catalysts were generously donated by Materia.", revision_no = "39", abstract = "α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/27654, title ="Total Syntheses of Cyanthiwigins B, F, and G", author = "Enquist, John A., Jr. and Virgil, Scot C.", journal = "Chemistry: a European Journal", volume = "17", number = "36", pages = "9957-9969", month = "August", year = "2011", doi = "10.1002/chem.201100425", issn = "0947-6539", url = "https://resolver.caltech.edu/CaltechAUTHORS:20111107-115520974", note = "© 2011 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.\n\nReceived: February 8, 2011; Published online: July 18, 2011.\n\nThis publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). The authors wish to thank NIH-NIGMS (R01M080269-01), Amgen, Abbott, Boehringer Ingelheim, Merck, and Bristol-Myers Squibbs, GlaxoSmithKline, Johnson and Johnson, Amgen, Merck Research Laboratories, Pfizer, Novartis, Roche, Abbott Laboratories, Boehringer-Ingelheim, AstraZeneca, and Caltech for financial support. We also wish to thank Dr. M. W. Day and Mr. L. M. Henling for X-ray crystallographic expertise, Dr. Andrew Harned, Dr. David White, Daniel Caspi, and J. T. Mohr for helpful discussions, and Professor Mark T. Hamann for authentic samples and spectra of cyanthiwigins B, F, and G. Ruthenium olefin metathesis catalysts were generously donated by Materia.", revision_no = "29", abstract = "A concise and versatile approach toward the preparation of the cyanthiwigin family of cyathane natural products is described. By leveraging a unique double asymmetric catalytic alkylation procedure it is possible to quickly establish two of the most critical stereocenters of the cyanthiwigin framework with high levels of selectivity and expediency. The synthetic route additionally employs both a tandem ring-closing cross-metathesis reaction, and an aldehyde-olefin radical cyclization process, in order to rapidly arrive at the tricyclic cyathane core of the cyanthiwigin molecules. From this unifying intermediate, the preparations of cyanthiwigins B, F, and G are attained swiftly and without the need for protecting groups.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/25300, title ="A Palladium-Catalyzed Vinylcyclopropane (3 + 2) Cycloaddition Approach to the Melodinus Alkaloids", author = "Goldberg, Alexander F. G. and Stoltz, Brian M.", journal = "Organic Letters", volume = "13", number = "16", pages = "4474-4476", month = "August", year = "2011", doi = "10.1021/ol2017615", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110912-114011217", note = "© 2011 American Chemical Society.\n\nPublished In Issue August 19, 2011; Article ASAP July 25, 2011; Received: June 30, 2011.\n\nThis publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). The authors wish to thank NIH-NIGMS(R01GM080269-01), Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. A.G. gratefully acknowledges the Natural Sciences and Engineering Research Council (NSERC) of Canada for a PGS D scholarship. Christopher Henry, Hosea Nelson, Kristy Tran, Florian Vogt, and Scott Virgil (Caltech) are thanked for helpful guidance. Lawrence Henling and Dr. Michael Day (Caltech) are gratefully acknowledged for X-ray crystallographic structural determination. The Bruker KAPPA APEXII X-ray diffractometer was purchased via an NSF CRIF:MU award to the California Institute of Technology, CHE-0639094. The Varian 400 MHz NMR spectrometer was purchased via an NIH grant (RR027690).", revision_no = "39", abstract = "A palladium-catalyzed (3 + 2) cycloaddition of a vinylcyclopropane and a β-nitrostyrene is employed to rapidly assemble the cyclopentane core of the Melodinus alkaloids. The ABCD ring system of the natural product family is prepared in six steps from commercially available materials.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/24731, title ="A rapid and convergent synthesis of the integrastatin core", author = "Tadross, Pamela M. and Bugga, Pradeep", journal = "Organic and Biomolecular Chemistry", volume = "9", number = "15", pages = "5354-5357", month = "August", year = "2011", doi = "10.1039/c1ob05725a", issn = "1477-0520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110808-112210599", note = "© 2011 The Royal Society of Chemistry.\nReceived 8th May 2011, Accepted 26th May 2011.\nFirst published on the web 26 May 2011.\n\nThis publication is based on work supported by Award No.\nKUS-11-006-02, made by King Abdullah University of Science\nand Technology (KAUST). Financial support from Caltech, the\nRose Hills Foundation (undergraduate fellowship to P.B.), and the\nCalifornia HIV/AIDS Research Program (graduate fellowship to\nP.M.T.) is also gratefully acknowledged.", revision_no = "16", abstract = "The tetracyclic core of the integrastatin natural products has\nbeen prepared in a convergent and rapidmanner. Our strategy\nrelies upon a palladium(II)-catalyzed oxidative cyclization to\nform the central [3.3.1]-dioxabicycle of the natural product\ncore. Overall, the core has been completed in only 4 linear\nsteps from known compounds.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/24168, title ="The Catalytic Enantioselective Total Synthesis of (+)-Liphagal", author = "Day, Joshua J. and McFadden, Ryan M.", journal = "Angewandte Chemie International Edition", volume = "50", number = "30", pages = "6814-6818", month = "July", year = "2011", doi = "10.1002/anie.201101842", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110622-115436125", note = "© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.\n\nReceived: March 15, 2011; Article first published online: 10 June 2011. \n\nThis publication is based on work supported by Award No. KUS-11-006-02, made by the King Abdullah University of Science and Technology (KAUST). We wish to thank the NIH-NIGMS (R01M080269-01), the Gordon and Betty Moore Foundation, Abbott, Amgen, Boehringer Ingelheim, and Caltech for generous funding. R.M.M. thanks Eli Lilly for a graduate fellowship. H.K. acknowledges the travelling scholarship of the Danish Technical University, the Jorcks foundation, and the Otto Mønsteds foundation for financial support. J.L.A. gratefully acknowledges the Amgen\nFoundation for funding through the Amgen Scholars program. We thank Prof. E. N. Jacobsen and Dr. S. J. Zuend for a kind donation of both (R)-t-leucine and their optimal Strecker catalyst.", revision_no = "33", abstract = "Ring a ding: The meroterpenoid natural product (+)-liphagal has been synthesized enantioselectively in 19 steps from commercially available materials. The trans-homodecalin system was achieved by ring expansion followed by stereoselective hydrogenation.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/24322, title ="Palladium-catalyzed, asymmetric Baeyer–Villiger oxidation of prochiral cyclobutanones with PHOX ligands", author = "Petersen, Kimberly S. and Stoltz, Brian M.", journal = "Tetrahedron", volume = "67", number = "24", pages = "4352-4357", month = "June", year = "2011", doi = "10.1016/j.tet.2011.04.046", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110706-135043254", note = "© 2011 Elsevier Ltd.\nReceived 28 February 2011; revised 11 April 2011; accepted 13 April 2011. Available online 23 April 2011. \n\nDedicated to Professor F. Dean Toste on the receipt of the 2011 Tetrahedron Young Investigator Award.\nThis publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and\nTechnology (KAUST).\n\n", revision_no = "15", abstract = "Described in this report is a general method for the conversion of prochiral 3-substituted cyclobutanones to enantioenriched γ-lactones through a palladium-catalyzed Baeyer–Villiger oxidation using phosphinooxazoline ligands in up to 99% yield and 81% ee. Lactones of enantiopurity ≥ 93% could be obtained through a single recrystallization step. Importantly, 3,3-disubtituted cyclobutanones produced enantioenriched lactones containing a β-quaternary center.\n\n", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/23941, title ="Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to Five-, Six-, and Seven-Membered β-Substituted Cyclic Enones: Enantioselective Construction of All-Carbon Quaternary Stereocenters\n", author = "Kikushima, Kotaro and Holder, Jeffrey C.", journal = "Journal of the American Chemical Society", volume = "133", number = "18", pages = "6902-6905", month = "May", year = "2011", doi = "10.1021/ja200664x", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110608-104503600", note = "© 2011 American Chemical Society. \n\nReceived: January 23, 2011. Published: April 15, 2011.\n\nThis publication is based on work supported by Award No.\nKUS-11-006-02, made by King Abdullah University of Science and\nTechnology (KAUST). The authors wish to thank NIH-NIGMS\n(R01GM080269-01), Amgen, Abbott, Boehringer Ingelheim, and\nCaltech for financial support. K.K. acknowledges the Japan Society\nfor the Promotion of Science for a postdoctoral fellowship. M.G. is\ngrateful to the Swiss National Science Foundation for financial\nsupport through a postdoctoral fellowship.", revision_no = "34", abstract = "The first enantioselective Pd-catalyzed construction of all-carbon quaternary stereocenters via 1,4-addition of arylboronic acids to β-substituted cyclic enones is reported. Reaction of a wide range of arylboronic acids and cyclic enones using a catalyst prepared from Pd(OCOCF_3)_2 and a chiral pyridinooxazoline ligand yields enantioenriched products bearing benzylic stereocenters. Notably, this transformation is tolerant to air and moisture, providing a practical and operationally simple method of synthesizing enantioenriched all-carbon quaternary stereocenters.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/23907, title ="Benzannulated Bicycles by Three-Component Aryne Reactions", author = "Allan, Kevin M. and Gilmore, Christopher D.", journal = "Angewandte Chemie International Edition", volume = "50", number = "19", pages = "4488-4491", month = "May", year = "2011", doi = "10.1002/anie.201100911", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110606-080601724", note = "© 2011 Wiley-VCH Verlag. Received: February 5, 2011. Article first published online: 11 Apr 2011. The authors thank Abbott, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Sigma–Aldrich, Teva, and Caltech for financial support. Lawrence Henling and Dr. Michael Day are gratefully acknowledged for X-ray crystallographic structural determination. The Bruker KAPPA APEX II X-ray diffractometer was purchased through an NSF CRIF:MU award to the California Institute of Technology, CHE-0639094. Dr. Scott C. Virgil is acknowledged for helpful discussions.", revision_no = "25", abstract = "Triple crown: A pair of three-component coupling reactions between arynes, isocyanides, and either activated alkynes or phenyl esters generates unusual iminoindenones or phenoxy iminoisobenzofurans (see scheme), the latter of which may be advanced to o-ketobenzamides by performing direct hydrolysis. The synthetic utility of these compounds is demonstrated in a rapid preparation of substituted dibenzoketocaprolactams.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/23803, title ="Confirmation of the absolute configuration of (-)-aurantioclavine", author = "Behenna, Douglas C. and Krishnan, Shyam", journal = "Tetrahedron Letters", volume = "52", number = "17", pages = "2152-2154", month = "April", year = "2011", doi = "10.1016/j.tetlet.2010.11.074 ", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110526-081657895", note = "© 2010 Elsevier Ltd. Available online 18 November 2010. Dedicated to Professor Harry H. Wasserman on behalf of his 90th birthday. This publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). Financial support from Caltech, Amgen, and the California TRDRP (postdoctoral fellowship to S.K.) is also gratefully\nacknowledged. The Bruker KAPPA APEXII X-ray diffractometer\nused in this study was purchased via an NSF CRIF:MU award to Caltech, CHE-0639094.", revision_no = "24", abstract = "We confirm our previous assignment of the absolute configuration of (−)-aurantioclavine as 7R by crystallographically characterizing an advanced 3-bromoindole intermediate reported in our previous synthesis. This analysis also provides additional support for our model of enantioinduction in the palladium(II)-catalyzed oxidative kinetic resolution of secondary alcohols.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/23240, title ="A General Approach to the Basiliolide/Transtaganolide Natural Products: Total Syntheses of Basiliolide B, epi-8-Basiliolide B, Transtaganolide C, and Transtaganolide D", author = "Nelson, Hosea M. and Murakami, Kei", journal = "Angewandte Chemie International Edition", volume = "50", number = "16", pages = "3688-3691", month = "April", year = "2011", doi = "10.1002/anie.201008003", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110404-113128218", note = "© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.\n\nReceived: December 18, 2010.\nArticle first published online: 25 Mar. 2011.\n\nThis publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). The authors wish to thank the NSF and Ford Foundation (predoctoral fellowship to H.M.N.), the Japan Society for the Promotion of Science (fellowship for K.M.), Amgen, Abbott, Boehringer Ingelheim, the Gordon and Betty Moore Foundation, and Caltech for financial support. Dr. J. T. Mohr is gratefully acknowledged for useful discussions. Larry Henling and Dr. Michael Day are acknowledged for X-ray analysis of 1\u2009a. The Bruker KAPPA APEXII X-ray diffractometer used in this study was purchased through an NSF CRIF:MU award to Caltech, CHE-0639094.", revision_no = "36", abstract = "In a flash: The total synthesis of transtaganolide and basiliolide natural products is achieved in three steps from achiral, monocyclic esters (see scheme). Featured in the syntheses are an Ireland-Claisen/Diels–Alder cascade and a novel methoxyacetylide coupling/cyclization sequence.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/23315, title ="Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways", author = "Chou, Tsui-Fen and Brown, Steve J.", journal = "Proceedings of the National Academy of Sciences of the United States of America", volume = "108", number = "12", pages = "4834-4839", month = "March", year = "2011", doi = "10.1073/pnas.1015312108", issn = "0027-8424", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110414-085357247", note = "© 2011 National Academy of Sciences. \n\nEdited by Randy King, Harvard University, Cambridge, MA, and accepted by the Editorial Board February 4, 2011 (received for review October 12, 2010). Published online before print March 7, 2011. \n\nWe thank A. Brunger for providing plasmids; G. Georg for a useful suggestion regarding high-throughput screen validation; C. Weihl for helpful discussions; P. Baillargeon and L. DeLuca for compound management; F. Parlati for critical reading of the manuscript; and H. Park, R. Oania, and D. Shimoda for technical assistance. National Institutes of Health (NIH) U54 Grant MH074404 funded Scripps personnel. The University of Kansas was supported by Award U54 HG005031-02 administered by the National Human Genome Research Institute on behalf of the NIH Roadmap Molecular Libraries Program. A.C.J. was supported by NIH Grant F32GM082000. T.-F.C. was supported by a 2008 Fellows Grant Program Award from the Multiple Myeloma Research Foundation, the Howard Hughes Medical Institute (HHMI), and the Weston Havens Foundation. R.J.D. is an HHMI Investigator, and this work was funded in part by HHMI and in part by NIH R03 Grant MH085687. \n\nAuthor contributions: T.-F.C., B.M.S., F.J.S., M.P.P., P.H., H.R., and R.J.D. designed research; T.-F.C., S.J.B., D.M., B.E.N., K.L., A.C.J., P.C., and P.R.P. performed research; T.-F.C. and R.J.D. analyzed data; and T.-F.C. and R.J.D. wrote the paper.", revision_no = "34", abstract = "A specific small-molecule inhibitor of p97 would provide an important tool to investigate diverse functions of this essential ATPase associated with diverse cellular activities (AAA) ATPase and to evaluate its potential to be a therapeutic target in human disease. We carried out a high-throughput screen to identify inhibitors of p97 ATPase activity. Dual-reporter cell lines that simultaneously express p97-dependent and p97-independent proteasome substrates were used to stratify inhibitors that emerged from the screen. N^2,N^4-dibenzylquinazoline-2,4-diamine (DBeQ) was identified as a selective, potent, reversible, and ATP-competitive p97 inhibitor. DBeQ blocks multiple processes that have been shown by RNAi to depend on p97, including degradation of ubiquitin fusion degradation and endoplasmic reticulum-associated degradation pathway reporters, as well as autophagosome maturation. DBeQ also potently inhibits cancer cell growth and is more rapid than a proteasome inhibitor at mobilizing the executioner caspases-3 and -7. Our results provide a rationale for targeting p97 in cancer therapy.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/23159, title ="Ring-Contraction Strategy for the Practical, Scalable, Catalytic Asymmetric Synthesis of Versatile γ-Quaternary Acylcyclopentenes", author = "Hong, Allen Y. and Krout, Michael R.", journal = "Angewandte Chemie International Edition", volume = "50", number = "12", pages = "2756-2760", month = "March", year = "2011", doi = "10.1002/anie.201007814", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110329-133407762", note = "© 2011 Wiley. Received: December 12, 2010. Article first published online: 24 Feb 2011. This publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). The authors wish to thank NIH-NIGMS (R01M080269-01), Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. M.R.K. acknowledges Eli Lilly for a predoctoral fellowship. T.J. acknowledges the Danish Council for\nIndependent Research/Natural Sciences for a postdoctoral fellowship. Materia, Inc. is gratefully acknowledged for the donation of catalysts. Lawrence Henling and Dr. Michael Day are gratefully acknowledged for X-ray crystallographic structure determination. The Bruker KAPPA APEXII X-ray diffractometer used in this study was purchased via an NSF CRIF:MU award to Caltech (CHE-0639094). Prof. Sarah Reisman, Dr. Scott Virgil, Dr. Christopher Henry, and Nathaniel Sherden are acknowledged for helpful discussions. Dr. David VanderVelde and Dr. Scott Ross are acknowledged for NMR assistance. The Varian 400 MR instrument used in this study was purchased via an NIH award to Caltech (NIH\nRR027690). Dr. Mona Shahgholi and Naseem Torian are acknowledged for high-resolution mass spectrometry assistance.", revision_no = "35", abstract = "Contraction action! A simple protocol for the catalytic asymmetric synthesis of highly functionalized γ-quaternary acylcyclopentenes (see schematic) in up to 91\u2009% overall yield and 92\u2009% ee has been developed. The reaction sequence employs a palladium-catalyzed enantioselective alkylation reaction and exploits the unusual stability of β-hydroxy cycloheptanones to achieve a general and robust method for performing two-carbon ring contractions.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/21943, title ="A Catalytic, Asymmetric Formal Synthesis of (+)-Hamigeran B", author = "Mukherjee, Herschel and McDougal, Nolan T.", journal = "Organic Letters", volume = "13", number = "5", pages = "825-827", month = "March", year = "2011", doi = "10.1021/ol102669z", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20110201-085102866", note = "© 2011 American Chemical Society.\n\nReceived December 8, 2010. Publication Date (Web): January 27, 2011. \n\nThis publication is based on work\nsupported by Award No. KUS-11-006-02, made by King\nAbdullah University of Science and Technology\n(KAUST). Additionally, the authors wish to thank NIHNIGMS\n(R01 GM 080269-01), Abbott Laboratories,\nAmgen, the Gordon and Betty Moore Foundation, and\nCaltech for financial support and Materia, Inc. for the kind\ndonation of catalyst 8. Dr. Douglas C. Behenna is gratefully\nacknowledged for assistance in the preparation of the\nmanuscript.", revision_no = "32", abstract = "A concise asymmetric, formal synthesis of (+)-hamigeran B is reported. A Pd-catalyzed, decarboxylative allylic alkylation, employing a trifluoromethylated derivative of t-BuPHOX, is utilized as the enantioselective step to form the critical quaternary carbon center in excellent yield and enantioselectivity. The product is converted in three steps to a late-stage intermediate previously used in the synthesis of hamigeran B.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/33245, title ="Complex natural products as a driving force for discovery in organic chemistry", author = "Stoltz, B. M.", month = "December", year = "2010", url = "https://resolver.caltech.edu/CaltechAUTHORS:20120816-071730866", note = "© 2012 American Chemical Society.", revision_no = "13", abstract = "This lecture will focus on the development of new catalytic bond forming reactions developed in our lab and applications\nin complex mol. synthesis.", } @conference_item {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/33242, title ="Intertwined nature of chemical synthesis and the discovery process", author = "Stoltz, B. M.", month = "December", year = "2010", url = "https://resolver.caltech.edu/CaltechAUTHORS:20120815-153559315", note = "© 2012 American Chemical Society.", revision_no = "12", abstract = "This lecture will describe recent advances in our lab. in the area of asym. catalysis and applications in multi-step\nsynthesis.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/20648, title ="Rapid synthesis of an electron-deficient t-BuPHOX ligand: cross-coupling of aryl bromides with secondary phosphine oxides", author = "McDougal, Nolan T. and Streuff, Jan", journal = "Tetrahedron Letters", volume = "51", number = "42", pages = "5550-5554", month = "October", year = "2010", doi = "10.1016/j.tetlet.2010.08.039", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20101103-104745366", note = "© 2010 Elsevier Ltd. \n\nReceived 13 May 2010; revised 11 August 2010; accepted 12 August 2010. Available online 17 August 2010. \n\nThis publication is based on the work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). Additionally, the authors wish to thank NIH-NIGMS (R01 GM 080269-01), the German Academic Exchange Service (DAAD, postdoctoral fellowship to J.S.), Abbott Laboratories, Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support.", revision_no = "21", abstract = "Herein an efficient and direct copper-catalyzed coupling of oxazoline-containing aryl bromides with electron-deficient secondary phosphine oxides is reported. The resulting tertiary phosphine oxides can be reduced to prepare a range of PHOX ligands. The presented strategy is a useful alternative to known methods for constructing PHOX derivatives.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/52995, title ="Welwitindolinone C synthetic studies. Construction of the welwitindolinone carbon skeleton via a transannular nitrone cycloaddition", author = "Freeman, David B. and Holubec, Alexandra A.", journal = "Tetrahedron", volume = "66", number = "33", pages = "6647-6655", month = "August", year = "2010", doi = "10.1016/j.tet.2010.04.131", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141217-164835707", note = "Copyright © 2010 Elsevier. \n\nReceived 1 March 2010; Received in revised form 21 April 2010; Accepted 29 April 2010; Available online 6 May 2010. \n\n2009 Tetrahedron Prize for Creativity in Organic Chemistry. \n\nDedicated to Professor Steven Ley, a friend and inspirational leader in organic chemistry. \n\nFunding from the NIH (1 RO1 CA 93591), Astellas (formerly Yamanouchi), Daiichi, and Fujisawa are gratefully acknowledged. MI thanks the University of Tokyo School of Agricultural Sciences. JLW thanks Amgen, Merck, Bristol-Myers Squibb, GlaxoSmithKline and Pfizer for research support. RNT would like to acknowledge the Jack and June Richardson Honors Scholarship Fund and the CSU CNS Undergraduate Scholarship Fund for financial support. Dr. Chris Incarvito, Dr. Chris Rithner, Don Heyse and Don Dick are acknowledged for their assistance with X-ray crystallography and instrumentation.", revision_no = "15", abstract = "Described is the construction of the N-methylwelwitindolinone C core via an efficient strategy that employs a sequential rhodium carbenoid-mediated O–H insertion, Claisen rearrangement and transannular [3+2] nitrone cycloaddition.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/19033, title ="High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction of Enolate-Stabilized Enol Carbonates", author = "McDougal, Nolan T. and Virgil, Scott C.", journal = "Synlett", volume = "2010", number = "11", pages = "1712-1716", month = "July", year = "2010", doi = "10.1055/s-0030-1258094 ", issn = "0936-5214", url = "https://resolver.caltech.edu/CaltechAUTHORS:20100713-135750673", note = "© 2010 Thieme Stuttgart.\n\nReceived 7 April 2010. \n\nThis publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). Additionally, the authors wish to thank NIH-NIGMS (R01 GM 080269-01), Abbott Laboratories, Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support.", revision_no = "17", abstract = "The use of high-throughput screening allowed for the optimization of reaction conditions for the palladium-catalyzed asymmetric decarboxylative alkylation reaction of enolate-stabilized enol carbonates. Changing to a nonpolar reaction solvent and to an electron-deficient PHOX derivative as ligand from our standard \u00adreaction conditions improved the enantioselectivity for the alkylation of a ketal-protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar improvements in enantioselectivity were seen for a β-keto ester derived and an α-phenyl cyclohexanone-\u00adderived enol carbonate.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/18501, title ="Efforts toward rapid construction of the cortistatin A carbocyclic core via enyne-ene metathesis", author = "Baumgartner, Corinne and Ma, Sandy", journal = "Organic and Biomolecular Chemistry", volume = "8", number = "13", pages = "2915-2917", month = "June", year = "2010", doi = "10.1039/c004275g", issn = "1477-0520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20100601-110245242", note = "© The Royal Society of Chemistry 2010. Received 17th March 2010, Accepted 4th May 2010. \nFirst published on the web 24th May 2010. C. B. thanks the Schweizerischer Nationalfonds (SNF) for a fellowship. This publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). Additionally, the authors thank Abbott, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, Sigma-Aldrich and Caltech for generous funding. Mr Lawrence Henling and Dr Michael Day are gratefully acknowledged for X-ray crystallographic structural determination. The Bruker KAPPA APEXII X-ray diffractometer was purchased via an NSF CRIF:MU award to the California Institute of Technology, CHE-0639094. Dr David VanderVelde and Dr Scott Ross are acknowledged for NMR assistance. Dr Scott Virgil is acknowledged for helpful discussions.", revision_no = "25", abstract = "Our efforts toward the construction of the carbocylic core of cortistatin A via an enyne-ene metathesis are\ndisclosed. Interestingly, an attempted S_N2 inversion of a secondary mesylate in our five-membered D-ring piece\ngave a product with retention of stereochemistry.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/19000, title ="A general enantioselective route to the chamigrene natural product family", author = "White, David E. and Stewart, Ian C.", journal = "Tetrahedron", volume = "66", number = "26", pages = "4668-4686 ", month = "June", year = "2010", doi = "10.1016/j.tet.2010.04.128", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20100712-150605717", note = "© 2010 Elsevier.\nReceived 15 April 2010; \nrevised 28 April 2010; \naccepted 29 April 2010. \nAvailable online 4 May 2010.\n\nThis publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). Additionally, the authors wish to thank the NIH-NIGMS (R01 GM080269-01, postdoctoral fellowships to D.E.W. and I.C.S.), Abbott, Amgen, Bristol-Myers Squibb, Merck, and Caltech for generous funding; Materia, Inc. for their kind donation of catalyst 49 used in these studies; Professors Mercedes Cueto and Karen L. Erickson for their kind donation of natural samples of elatol (1); Professor Adusumilli Srikrishna for copies of 1H and 13C NMR spectra of synthetic (±)-laurencenone C ((±)-8) and (±)-α-chamigrene ((±)-5); and Professor Peter B. Dervan and David M. Chenoweth for use of their HPLC. Finally, B.M.S. thanks all of his current and former co-workers and colleagues who have made working at Caltech over the past 10 years such an enjoyable experience. As evidenced by the collaborative nature of this project, the spectacular environment at Caltech is one-of-a-kind and second-to-none.", revision_no = "24", abstract = "Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/18475, title ="NMR Chemical Shifts of Trace Impurities: Common\nLaboratory Solvents, Organics, and Gases in Deuterated\nSolvents Relevant to the Organometallic\nChemist", author = "Fulmer, Gregory R. and Miller, Alexander J. M.", journal = "Organometallics", volume = "29", number = "9", pages = "2176-2179", month = "May", year = "2010", doi = "10.1021/om100106e", issn = "0276-7333", url = "https://resolver.caltech.edu/CaltechAUTHORS:20100527-094834306", note = "© 2010 American Chemical Society. \n\nPublished In Issue May 10, 2010. Received February 11, 2010. Publication Date (Web): April 16, 2010. Article ASAP April 16, 2010. \n\nG.R.F. and K.I.G. thank the Department of Energy (Contract No. DE-FG02-06ER15765) for support. A.J.M.M. and J.E.B. thank the Moore Foundation for support. N.H.S. and B.M.S. thank Abbott Laboratories, Amgen, Merck, Bristol-Myers Squibb, Boehringer Ingelheim, the Gordon and Betty Moore Foundation, and Caltech for financial support.", revision_no = "24", abstract = "Tables of ^1H and ^(13)C NMR chemical shifts have been compiled for common organic compounds often used as reagents or found as products or contaminants in deuterated organic solvents. Building upon the work of Gottlieb, Kotlyar, and Nudelman in the Journal of Organic Chemistry, signals for common impurities are now reported in additional NMR solvents (tetrahydrofuran-d_8, toluene-d_8, dichloromethane-d_2, chlorobenzene-d_5, and 2,2,2-trifluoroethanol-d_3) which are frequently used in organometallic laboratories. Chemical shifts for other organics which are often used as reagents or internal standards or are found as products in organometallic chemistry are also reported for all the listed solvents.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/17954, title ="Aryne Acyl-Alkylation in the General and Convergent Synthesis of Benzannulated Macrolactone Natural Products: An Enantioselective Synthesis of (−)-Curvularin", author = "Tadross, Pamela M. and Virgil, Scott C.", journal = "Organic Letters", volume = "12", number = "7", pages = "1612-1614", month = "April", year = "2010", doi = "10.1021/ol100335y ", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20100413-105259618", note = "© 2010 American Chemical Society.\nPublished In Issue April 02, 2010; Article ASAP March 02, 2010; Received: February 9, 2010.\nPublication Date (Web): March 2, 2010.\nWe thank The Gordon and Betty\nMoore Foundation, Abbott, Amgen, Boehringer-Ingelheim,\nBristol-Myers Squibb, Merck, Sigma-Aldrich, The California\nHIV/AIDS Research Program (fellowship to P.M.T.), and\nCaltech for generous funding.", revision_no = "20", abstract = "A general approach for the synthesis of benzannulated macrolactone natural products utilizing an aryne acyl-alkylation reaction is described. Toward this end, the total syntheses of the natural products (−)-curvularin, curvulin, and (−)-diplodialide C are reported. Furthermore, the aryne insertion technology has enabled the rapid conversion of simple diplodialide natural products to curvularin, thereby connecting these two biosynthetically distinct classes of compounds via synthetic methods.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/17854, title ="Regioselective Reactions of Highly Substituted Arynes", author = "Tadross, Pamela M. and Gilmore, Christopher D.", journal = "Organic Letters", volume = "12", number = "6", pages = "1224-1227", month = "March", year = "2010", doi = "10.1021/ol1000796", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20100405-115154177", note = "© 2010 American Chemical Society.\n\nPublished In Issue: March 19, 2010; article ASAP: February 18, 2010; received: January 12, 2010.\n\nThe authors thank The Gordon and\nBetty Moore Foundation, Abbott, Amgen, Boehringer-\nIngelheim, Bristol-Myers Squibb, Merck, Sigma-Aldrich,\nTeva USA Scholars grant, The California HIV/AIDS Research\nProgram (fellowship to P.M.T.) and Caltech for\ngenerous funding.", revision_no = "19", abstract = "The fully regioselective reactivity of four new highly substituted silyl aryl triflate aryne precursors in aryne acyl-alkylation, acyl-alkylation/condensation, and heteroannulation reactions is reported. The application of these more complex arynes provides access to diverse natural product scaffolds and obviates late-stage functionalization of aromatic rings.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/17682, title ="A palladium-catalysed enolate alkylation cascade for the formation of adjacent quaternary and tertiary stereocentres", author = "Streuff, Jan and White, David E.", journal = "Nature Chemistry", volume = "2", number = "3", pages = "192-196", month = "March", year = "2010", doi = "10.1038/nchem.518", issn = "1755-4330", url = "https://resolver.caltech.edu/CaltechAUTHORS:20100305-152223080", note = "© 2010 Nature Publishing Group.\n\nReceived 7 September 2009; accepted 4 December 2009;\npublished online 31 January 2010.\n\nThe authors thank the National Institute of Health’s National Institute of General Medical\nSciences (R01 GM 080269-01 and a postdoctoral fellowship to D.E.W.), the German\nAcademic Exchange Service (DAAD, postdoctoral fellowship to J.S.), Abbott Laboratories,\nAmgen, Merck, Bristol-Myers Squibb, Boehringer Ingelheim, the Gordon and Betty Moore\nFoundation and Caltech for financial support. We thank S. Reisman for discussions.\nL. Henling and M. Day carried out the X-ray crystallographic analysis. The Bruker KAPPA\nAPEXII X-ray diffractometer was purchased with a National Science Foundation\nChemistry Research Instrumentation and Facilities: Departmental Multi-User\nInstrumentation award to the California Institute of Technology (CHE-0639094).\nJ.S. planned and carried out the experimental work and wrote the manuscript. D.E.W. and\nS.C.V. took part in the initial reaction development and screening experiments. B.M.S.\ninitiated and directed the project. All authors commented on the manuscript.\nThe authors declare no competing financial interests. Supplementary information and\nchemical compound information accompany this paper at www.nature.com/\nnaturechemistry. Reprints and permission information is available online at http://npg.nature.\ncom/reprintsandpermissions/. Correspondence and requests for materials should be\naddressed to B.M.S.", revision_no = "29", abstract = "The catalytic enantioselective synthesis of densely functionalized organic molecules that contain all-carbon quaternary stereocentres is a challenge to modern chemical methodology. The catalytically controlled, asymmetric α-alkylation of ketones represents another difficult task and is of major interest to our and other research groups. We report here a palladium-catalysed enantioselective process that addresses both problems simultaneously and allows the installation of vicinal all-carbon quaternary and tertiary stereocentres at the α-carbon of a ketone in a single step. This multiple bond-forming process is carried out on readily available β-ketoester starting materials and proceeds by conjugate addition of a palladium enolate, generated in situ, to activated Michael acceptors. As a result, the CO_2 moiety of the substrate is displaced by a C–C fragment in an asymmetric cut-and-paste reaction with high yield, diastereomeric ratio and enantiomeric excess.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/16970, title ="Expedient synthesis of 3-hydroxyisoquinolines and 2-hydroxy-1,4-naphthoquinones via one-pot aryne acyl-alkylation/condensation", author = "Allan, Kevin M. and Hong, Boram D.", journal = "Organic and Biomolecular Chemistry", volume = "7", number = "23", pages = "4960-4964", month = "December", year = "2009", doi = "10.1039/b913336d", issn = "1477-0520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20091214-081131773", note = "© Royal Society of Chemistry 2009. \nReceived 6th July 2009, Accepted 9th September 2009. First published on the web 6th October 2009. \n\nThe authors gratefully acknowledge Pamela M. Tadross and Scott C. Virgil for helpful discussions and experimental assistance. The authors thank Abbott, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, Sigma-Aldrich and Caltech for generous funding. \n\nElectronic supplementary information (ESI) available: General experimental procedures, characterization data, NMR, and IR spectra. See DOI:\n10.1039/b913336d", revision_no = "21", abstract = "A convenient method is disclosed for the synthesis of both 3-hydroxyisoquinolines and 2-hydroxy-1,4-naphthoquinones from b-ketoesters using a one-pot aryne acyl-alkylation/condensation procedure. When performed in conjunction with a one-step method for the synthesis of the b-ketoester substrates, this method provides a new route to these polyaromatic structures in only two steps from commercially available carboxylic acid starting materials. The utility of this approach is demonstrated\nin the synthesis of the atropisomeric P,N-ligand, QUINAP.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/17525, title ="The Palladium-Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications", author = "Ebner, David C. and Bagdanoff, Jeffrey T.", journal = "Chemistry: a European Journal", volume = "15", number = "47", pages = "12978-12992", month = "December", year = "2009", doi = "10.1002/chem.200902172 ", issn = "0947-6539", url = "https://resolver.caltech.edu/CaltechAUTHORS:20100218-140616247", note = "© 2009 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim. \n\nReceived: August 5, 2009. Published online: November 10, 2009. \n\nThe authors are grateful to the NDSEG (predoctoral fellowship to D.C.E.), the NSF (predoctoral fellowships to D.C.E. and E.M.F.), the University of California TRDRP (predoctoral fellowship to J.T.B.), Bristol-Myers Squibb Company (predoctoral fellowship to E.M.F.), the American Chemical Society Division of Organic Chemistry and Bristol-Myers Squibb Foundation (predoctoral fellowship to R.M.T.), Eli Lilly (predoctoral fellowships to D.D.C. and R.M.M.), the NIH-NIGMS (R01GM65961-01), King Abdullah University of Science and Technology (KAUST, Award No. KUS-I1-006–02), California Institute of Technology, A. P. Sloan Foundation, the Dreyfus Foundation, Research Corporation, Abbott, Amgen, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Johnson and Johnson, Eli Lilly, Merck, Novartis, Pfizer, and Roche for generous funding.", revision_no = "27", abstract = "The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (-)-sparteine as a chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of the base and hydrogen-bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions. The use of chloroform as solvent allows the use of ambient air as the terminal oxidant at 23 °C, resulting in enhanced catalyst selectivity. These improved reaction conditions have permitted the successful kinetic resolution of benzylic, allylic, and cyclopropyl secondary alcohols to high enantiomeric excess with good-to-excellent selectivity factors. This catalyst system has also been applied to the desymmetrization of meso-diols, providing high yields of enantioenriched hydroxyketones.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/16164, title ="Catalytic Enantioselective Stereoablative Alkylation of 3-Halooxindoles: Facile Access to Oxindoles with C3 All-Carbon Quaternary Stereocenters", author = "Ma, Sandy and Han, Xiaoqing", journal = "Angewandte Chemie International Edition", volume = "48", number = "1", pages = "1-6", month = "September", year = "2009", doi = "10.1002/anie.200902943 ", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20091002-090709845", note = "© 2009 WILEY. Received: 1 June 2009. We wish to thank the California TRDRP (postdoctoral fellowships to X.H. and S.K.), Abbott Laboratories, Amgen, Merck, Bristol-Myers Squibb, Boehringer Ingelheim, the Gordon and Betty Moore Foundation, and Caltech for financial support. Lawrence Henling and Dr. Michael Day are gratefully acknowledged for X-ray crystallographic structure determination. Prof. David Horne is thanked for helpful discussions. The Bruker KAPPA APEX II X-ray diffractometer was purchased through an NSF CRIF:MU award to the California Institute of Technology, CHE-0639094. Dr. David VanderVelde and Dr. Scott Ross are acknowledged for NMR assistance.", revision_no = "30", abstract = "From 2 to 1! Racemic tertiary halooxindoles proceed to enantioenriched oxindoles bearing all-carbon quaternary stereocenters as a result of a catalytic enantioselective stereoablative process (see scheme). The application of this procedure allows for the rapid asymmetric construction of biologically significant alkaloid core motifs.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/16245, title ="Unusual Allylpalladium Carboxylate Complexes: Identification of the Resting State of Catalytic Enantioselective Decarboxylative Allylic Alkylation Reactions of Ketones", author = "Sherden, Nathaniel H. and Behenna, Douglas C.", journal = "Angewandte Chemie International Edition", volume = "48", number = "37", pages = "6840-6843", month = "September", year = "2009", doi = "10.1002/anie.200902575", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20091012-124240065", note = "Copyright © 2009 WILEY-VCH. \n\nReceived: 14 May 2009; Revised: 5 July 2009. Published Online: 11 August 2009. \n\nWe thank NIH-NIGMS (R01 GM 080269-01), Abbott Laboratories, Amgen, Merck, Bristol-Myers Squibb, Boehringer Ingelheim, the Fannie and John Hertz Foundation (predoctoral fellowship to DCB), the Gordon and Betty Moore Foundation, and Caltech for financial support. Lawrence Henling and Dr. Michael Day are gratefully acknowledged for X-ray crystallographic structural determination. The Bruker KAPPA APEX II X-ray diffractometer was purchased through an NSF CRIF:MU award to the California Institute of Technology, CHE-0639094. Prof. J. E. Bercaw, Prof. R. H. Grubbs, Prof. S. E. Reisman, Prof. W. A. Goddard III, and Dr. J. A. Keith are acknowledged for helpful discussions. Dr. David Vander Velde and Dr. Scott Ross are thanked for helpful assistance related to NMR.", revision_no = "20", abstract = "Palladium pop rocks: Hold on to your CO2! Enantioselective palladium-catalyzed decarboxylative alkylation of ketone enolates proceeds via 1-σ-allyl palladium-carboxylate complexes, such as 1 (Pd yellow, O red, N blue, P purple), by slow loss of CO_2. Reminiscent of pop rock candy, impure samples of 1 expel a gas (presumably CO_2) in the solid state and effervesce in solution.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/15140, title ="An efficient synthesis of the carbocyclic core of zoanthenol", author = "Stockdill, Jennifer L. and Behenna, Douglas C.", journal = "Tetrahedron", volume = "65", number = "33", pages = "6571-6575", month = "August", year = "2009", doi = "10.1016/j.tet.2009.05.023", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20090817-150141765", note = "© 2009 Elsevier Ltd. \n\nReceived 18 March 2009; revised 1 May 2009; accepted 8 May 2009. Available online 18 May 2009. \n\nThe authors wish to thank Novartis (graduate fellowship to J.L.S.), the Philanthropic Education Organization (Scholar Award to J.L.S.), the Fannie and John Hertz Foundation (graduate fellowship to D.C.B.), Abbott, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, and Caltech for their generous financial support. Additionally, we acknowledge Prof. Li Deng of Brandeis University for the kind donation of O-(−)-(menthyl acetate)quinidine and for helpful discussions. \n\nDedicated to Professor Larry E. Overman on the occasion of his receipt of the Tetrahedron Prize.", revision_no = "18", abstract = "A concise strategy for the synthesis of the carbocyclic portion of zoanthenol is disclosed. The key step involves a 6-endo radical-mediated conjugate addition that constructs the quaternary stereocenter at C(12) and closes the B ring in a stereoselective manner. The synthesis of the C-ring fragment uses an enantioselective desymmetrization to simultaneously establish the absolute stereochemistry of two vicinal quaternary stereocenters. In only 17 steps from known compounds, the route affords an ABC ring system containing all three quaternary stereocenters and appropriate functionality to complete the synthesis of zoanthenol.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/15447, title ="Enantioselective protonation", author = "Mohr, Justin T. and Hong, Allen Y.", journal = "Nature Chemistry", volume = "1", number = "5", pages = "359-369", month = "August", year = "2009", doi = "10.1038/nchem.297", issn = "1755-4330", url = "https://resolver.caltech.edu/CaltechAUTHORS:20090828-231033230", note = "© 2009 Nature Publishing Group. \n\nPublished online: 24 July 2009. \n\nWe thank the National Institutes of Health, National Institute of General Medical Sciences (grant number R01GM080269-01), Eli Lilly (predoctoral fellowship to J.T.M.), Amgen, Abbott Laboratories, Boehringer Ingelheim, Merck, Bristol-Myers Squibb and the California Institute of Technology for financial support.", revision_no = "20", abstract = "Enantioselective protonation is a common process in biosynthetic sequences. The decarboxylase and esterase enzymes that effect this valuable transformation are able to control both the steric environment around the proton acceptor (typically an enolate) and the proton donor (typically a thiol). Recently, several chemical methods for achieving enantioselective protonation have been developed by exploiting various means of enantiocontrol in different mechanisms. These laboratory transformations have proved useful for the preparation of a number of valuable organic compounds. Here, we review recent reports of enantioselective protonations, classifying them according to mechanism, and discuss how a deeper understanding of the processes can lead to improved methods for effecting this most fundamental method of obtaining enantiopure compounds.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/15702, title ="Unexpected decarbonylation during an acid-mediated cyclization to access the carbocyclic core of zoanthenol\n", author = "Stockdill, Jennifer L. and Behenna, Douglas C.", journal = "Tetrahedron Letters", volume = "50", number = "26", pages = "3182-3184", month = "July", year = "2009", doi = "10.1016/j.tetlet.2009.01.121", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20090909-132757912", note = "© 2009 Elsevier. \n\nReceived 17 January 2009; accepted 21 January 2009. Available online 29 January 2009. \n\nThe authors wish to thank Novartis (predoctoral fellowship to JLS), the Philanthropic Education Organization (Scholar Award to JLS), the John and Fannie Hertz Foundation (predoctoral fellowship to DCB), and Abbott, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, and Caltech for their generous financial support. The authors acknowledge Dr. Andrew McClory for experimental assistance and helpful discussions. Special thanks to Professor Andrew S. Kende for a stimulating discussion regarding the mechanism in Scheme 5. \n\nSupplementary data associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2009.01.121.", revision_no = "21", abstract = "An unusual loss of CO was observed during a key cyclization event in efforts toward the total synthesis of zoanthenol. The synthesis of the cyclization precursor and a proposed mechanism for decarbonylation are detailed.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/14698, title ="Synthetic efforts toward cyathane diterpenoid natural products", author = "Enquist, John A. and Stoltz, Brian M.", journal = "Natural Product Reports", volume = "26", number = "5", pages = "661-680", month = "May", year = "2009", doi = "10.1039/b811227b", issn = "0265-0568", url = "https://resolver.caltech.edu/CaltechAUTHORS:20090728-105816044", note = "© 2009 The Royal Society of Chemistry. \n\nReceived 20th December 2008. First published as an Advance Article on the web 16th March 2009. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269-01), Amgen, Abbott, Boehringer Ingelheim, Merck, and Bristol-Myers Squibb for financial support. JAE extends his thanks to Roche for support in the form of the excellence in chemistry award.", revision_no = "21", abstract = "An overview of synthetic efforts toward cyathane diterpenoid natural products from the year 2000 to present is provided. The emphasis of this review is the various ring-constructing and stereoforming strategies employed in these synthetic routes.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/15833, title ="Progress toward the synthesis of the transtaganolide/basiliolide natural products: an Ireland–Claisen approach", author = "Nelson, Hosea M. and Stoltz, Brian M.", journal = "Tetrahedron Letters", volume = "50", number = "15", pages = "1699-1701", month = "April", year = "2009", doi = "10.1016/j.tetlet.2009.01.108", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20090914-100459696", note = "Copyright © 2009 Elsevier. \n\nReceived 16 January 2009; accepted 19 January 2009. Available online 23 January 2009. \n\nWe thank the Ford Foundation (predoctoral fellowship to H.M.N.), National Science Foundation (predoctoral fellowship to H.M.N.), Abbott, Amgen, Bristol-Myers Squibb, Merck, Boehringer Ingelheim, and Caltech for generous funding.", revision_no = "20", abstract = "Efforts toward the synthesis of the transtaganolide natural product family are described. A highly efficient Ireland–Claisen/Diels–Alder approach has been developed, which rapidly constructs the highly oxygenated and stereochemically rich core of these natural products.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/14471, title ="Side chain chemistry mediates backbone fragmentation in hydrogen deficient peptide radicals", author = "Sun, Qingyu and Nelson, Hosea", journal = "Journal of Proteome Research", volume = "8", number = "2", pages = "958-966", month = "February", year = "2009", doi = "10.1021/pr800592t", issn = "1535-3893", url = "https://resolver.caltech.edu/CaltechAUTHORS:20090630-151621799", note = "© 2008 American Chemical Society.\nReceived August 4, 2008.\nPublication Date (Web): December 29, 2008.\n\nThe authors thank the National\nScience Foundation for funding (CHE-0747481 for R.R.J.).\nH.N. thanks the Ford Foundation for a predoctoral scholarship.\nB.M.S. and H.N. thank Caltech for funding. \n\n Supporting Information: Additional mass spectra and the mechanism for c and z formation. This material is available free of charge via the Internet at http://pubs.acs.org.", revision_no = "27", abstract = "A crown ether based, photolabile radical precursor which forms noncovalent complexes with peptides has been prepared. The peptide/precursor complexes can be electrosprayed, isolated in an ion trap, and then subjected to laser photolysis and collision induced dissociation to generate hydrogen deficient peptide radicals. It is demonstrated that these peptide radicals behave very differently from the hydrogen rich peptide radicals generated by electron capture methods. In fact, it is shown that side chain chemistry dictates both the occurrence and relative abundance of backbone fragments that are observed. Fragmentation at aromatic residues occurs preferentially over most other amino acids. The origin of this selectivity relates to the mechanism by which backbone dissociation is initiated. The first step is abstraction of a β-hydrogen from the side chain, followed by beta-elimination to yield primarily a-type fragment ions. Calculations reveal that those side chains which can easily lose a β-hydrogen correlate well with experimentally favored sites for backbone fragmentation. In addition, radical mediated side chain losses from the parent peptide are frequently observed. Eleven amino acids exhibit unique mass losses from side chains which positively identify that particular amino acid as part of the parent peptide. Therefore, side chain losses allow one to unambiguously narrow the possible sequences for a parent peptide, which when combined with predictable backbone fragmentation should lead to greatly increased confidence in peptide identification.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/98394, title ="The direct acyl-alkylation of arynes. Preparation of methyl 2-(2-acetylphenyl)acetate", author = "Ebner, David C. and Tambar, Uttam K.", journal = "Organic Syntheses", volume = "86", pages = "161-171", month = "January", year = "2009", doi = "10.15227/orgsyn.086.0161", issn = "2333-3553", url = "https://resolver.caltech.edu/CaltechAUTHORS:20190903-130240760", note = "© 2009, Organic Syntheses, Inc.", revision_no = "10", abstract = "[no abstract]", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/13592, title ="Catalytic enantioselective approach to the eudesmane sesquiterpenoids: total synthesis of (+)-carissone", author = "Levine, Samantha R. and Krout, Michael R.", journal = "Organic Letters", volume = "11", number = "2", pages = "289-292", month = "January", year = "2009", doi = "10.1021/ol802409h", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:LEVol09", note = "© 2008 American Chemical Society. \n\nReceived October 19, 2008. \n\nWe thank Krastina V. Petrova and Justin T. Mohr (Caltech) for helpful discussions and experimental assistance. We gratefully acknowledge the NIH-NIGMS (RO1GM080269-01), Marcella R. Bonsall and the Dalton Fund (undergraduate fellowships to S.R.L.), Eli Lilly (predoctoral fellowship to M.R.K.), Amgen, Abbott Laboratories, Boehringer-Ingelheim, Materia, Merck, Bristol-Meyers Squibb, and the California Institute of Technology for financial support.", revision_no = "28", abstract = "A catalytic enantioselective approach to the eudesmane sesquiterpenoids is reported. The strategic use of a palladium-catalyzed enantioselective alkylation of vinylogous ester substrates forged the C(10) all-carbon quaternary center. This key transformation enabled a diastereoselective olefin hydrogenation to create the syn stereochemistry at C(7). The devised synthetic strategy allowed for the preparation of the antibacterial agent (+)-carissone and a formal synthesis of the P/Q-type calcium channel blocker (-)-α-eudesmol.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/13319, title ="Enantioselective Total Synthesis of (+)-Cassiol", author = "Petrova, Krastina V. and Mohr, Justin T.", journal = "Organic Letters", volume = "11", number = "2", pages = "293-295", month = "January", year = "2009", doi = "10.1021/ol802410t", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:PETol09", note = "© 2008 American Chemical Society. \n\nReceived October 19, 2008. \n\nWe thank Samantha R. Levine and Michael R. Krout (Caltech) for helpful discussions and experimental assistance. We thank the NIH-NIGMS (R01 GM080269-01), Caltech Amgen Scholars Program (undergraduate fellowship to K.V.P.), Eli Lilly (predoctoral fellowship to J.T.M.), Amgen, Bristol-Myers Squibb, Merck Research Laboratories, Abbott Laboratories, Boehringer-Ingelheim, and Caltech for financial support.", revision_no = "29", abstract = "An enantioselective total synthesis of (+)-cassiol is reported. The complex derived from Pd-2(pmdba)(3) and enantiopure t-BuPHOX ligand catalyzes enantioconvergent decarboxylative alkylation to generate the quaternary carbon stereocenter at an early stage. The overall synthetic strategy involves a convergent late-stage coupling of two fragments. The synthesis features a longest linear sequence of eight steps.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/53218, title ="Preparation of (S)-2-Allyl-2-methylcyclohexanone (Cyclohexanone, 2-methyl-2-(2-propen-1-yl)-, (2S)-)", author = "Mohr, Justin T. and Krout, Michael R.", journal = "Organic Syntheses", volume = "86", pages = "194-211", month = "January", year = "2009", doi = "10.15227/orgsyn.086.0194", issn = "0078-6209", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150106-134315572", note = "© 2009 Organic Syntheses, Inc.", revision_no = "15", abstract = "[No abstract]", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/53146, title ="Preparation of (S)-tert-ButylPHOX (Oxazole, 4-(1,1-dimethylethyl)-2-[2-(diphenylphosphino)phenyl]-4,5-dihydro- (4S)-)", author = "Stoltz, Brian M. and Krout, Michael R.", journal = "Organic Syntheses", volume = "86", pages = "181-193", month = "January", year = "2009", doi = "10.15227/orgsyn.086.0181", issn = "0078-6209", url = "https://resolver.caltech.edu/CaltechAUTHORS:20141223-105727889", note = "© 2009 Organic Syntheses, Inc.", revision_no = "20", abstract = "[No abstract]", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/14785, title ="A concise total synthesis of (−)-quinocarcin via aryne annulation", author = "Allan, Kevin M. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "130", number = "51", pages = "17270-17271", month = "November", year = "2008", doi = "10.1021/ja808112y", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20090804-102608108", note = "© 2008 American Chemical Society. Received October 14, 2008; E-mail: stoltz@caltech.edu. The authors thank Abbott, Amgen, Boehringer-\nIngelheim, Bristol-Myers Squibb, Merck, Sigma-Aldrich, and Caltech for\ngenerous funding. Special thanks to Dr. Scott C. Virgil of the Caltech\nCenter for Catalysis and Chemical Synthesis for helpful discussions.", revision_no = "27", abstract = "Described in this report is a rapid asymmetric total synthesis of the tetrahydroisoquinoline antitumor antibiotic (−)-quinocarcin. The sequence employs a mild fluoride-induced aryne annulation developed in our laboratories to build a key isoquinoline-containing intermediate comprising the entire carbon scaffold of the natural product. This intermediate is advanced through six additional steps to the target alkaloid, providing the shortest synthetic route to (−)-quinocarcin reported to date.\n", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/14705, title ="Structural features and reactivity of (sparteine)PdCl_2: a model for selectivity in the oxidative kinetic resolution of secondary alcohols", author = "Trend, Raissa M. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "130", number = "47", pages = "15957-15966", month = "November", year = "2008", doi = "10.1021/ja804955e", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20090728-134418790", note = "© 2009 American Chemical Society. \n\nReceived June 27, 2008. \n\nThis work is dedicated to the memory of Prof. Nelson J. Leonard. The authors thank the NIH-NIGMS (R01 GM65961-01), Bristol-Myers Squibb Co. and the American Chemical Society (graduate fellowship to R.M.T.), Merck Research Laboratories, Abbott Laboratories, Pfizer, Amgen, Boehringer Ingelheim, GlaxoSmithKline, Lilly, and Johnson and Johnson for generous financial support. Mr. Lawrence Henling and Dr. Michael\nDay are gratefully acknowledged for X-ray crystallographic structural determination.", revision_no = "56", abstract = "The chiral ligand (−)-sparteine and PdCl_2 catalyze the enantioselective oxidation of secondary alcohols to ketones and thus effect a kinetic resolution. The structural features of sparteine that led to the selectivity observed in the reaction were not clear. Substitution experiments with pyridine derivatives and structural studies of the complexes generated were carried out on (sparteine)PdCl2 and indicated that the C1 symmetry of (−)-sparteine is essential to the location of substitution at the metal center. Palladium alkoxides were synthesized from secondary alcohols that are relevant steric models for the kinetic resolution. The solid-state structures of the alkoxides also confirmed the results from the pyridine derivative substitution studies. A model for enantioinduction was developed with C1 symmetry and Cl− as key features. Further studies of the diastereomers of (−)-sparteine, (−)-α-iso- and (+)-β-isosparteine, in the kinetic resolution showed that these C_2-symmetric counterparts are inferior ligands in this stereoablative reaction ", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/13587, title ="Pd-catalyzed enantioselective aerobic oxidation of secondary alcohols: Applications to the total synthesis of alkaloids", author = "Krishnan, Shyam and Bagdanoff, Jeffrey T.", journal = "Journal of the American Chemical Society", volume = "130", number = "41", pages = "13745-13754", month = "October", year = "2008", doi = "10.1021/ja804738b", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:KRIjacs08", note = "© 2008 American Chemical Society.\nReceived June 20, 2008.\nThe authors thank the NIH-NIGMS (R01\nGM65961-01), California TRDRP (postdoctoral fellowships to\nY.K.R. and S.K., and predoctoral fellowship to J.T.B.), NDSEG\n(predoctoral fellowships to D.C.E. and U.K.T.), NSF (predoctoral\nfellowship to D.C.E.), Caltech, AstraZeneca, Boehringer Ingelheim,\nJohnson & Johnson, Pfizer, Merck, Amgen, Abbott, Research\nCorporation, Roche, and GlaxoSmithKline for generous funding", revision_no = "28", abstract = "Enantioselective syntheses of the alkaloids (-)-aurantioclavine, (+)-amurensinine, (-)-lobeline, and (-)- and (+)-sedamine are described. The syntheses demonstrate the effectiveness of the Pd-catalyzed asymmetric oxidation of secondary alcohols in diverse contexts and the ability of this methodology to set the absolute configuration of multiple stereocenters in a single operation. The utility of an aryne C-C insertion reaction in accessing complex polycyclic frameworks is also described.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/13392, title ="Natural products as inspiration for the development of asymmetric catalysis", author = "Mohr, Justin T. and Krout, Michael R.", journal = "Nature", volume = "455", number = "7211", pages = "323-332", month = "September", year = "2008", doi = "10.1038/nature07370", issn = "0028-0836", url = "https://resolver.caltech.edu/CaltechAUTHORS:MOHnat08", note = "© 2008 Nature Publishing Group. \n\nWe thank the National Institute of General Medical Sciences\n(grant number R01GM080269-01), Eli Lilly (which provided predoctoral\nfellowships to J.T.M. and M.R.K.), Amgen, Abbott Laboratories, Boehringer Ingelheim, Merck, Bristol–Myers Squibb and the California Institute of Technology\nfor financial support.", revision_no = "26", abstract = "Biologically active natural products often contain particularly challenging structural features and\nfunctionalities in terms of synthesis. Perhaps the greatest difficulties are those caused by issues of\nstereochemistry. A useful strategy for synthesizing such molecules is to devise methods of bond formation\nthat provide opportunities for using enantioselective catalysis. In using this tactic, the desire for a particular\ntarget structure ultimately drives the development of catalytic methods. New enantioselective catalytic\nmethods contribute to a greater fundamental understanding of how bonds can be constructed and lead to valuable synthetic technologies that are useful for a variety of applications.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74346, title ="Catalytic Enantioselective Alkylation of Substituted Dioxanone Enol Ethers: Ready Access to C(α)-Tetrasubstituted Hydroxyketones, Acids, and Esters", author = "Seto, Masaki and Roizen, Jennifer L.", journal = "Angewandte Chemie International Edition", volume = "47", number = "36", pages = "6873-6876", month = "August", year = "2008", doi = "10.1002/anie.200801424", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-154336630", note = "© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nReceived: March 25, 2008; Revised: May 1, 2008; Published online: July 24, 2008. \n\nThe authors thank the Takeda Pharmaceutical Company Limited of Japan (postdoctoral fellowship to M.S.), the California Tobacco-Related Disease Research Program of the University of California, Grant Number 14DT-0004 (predoctoral fellowship to J.L.R.), the NIH-NIGMS (R01 GM 080269-01), and Caltech for financial support, Materia, Inc. for their generous donation of catalyst 9 used in these studies, and Dr. S. Virgil, A. Silberstein, and Y. Segawa for experimental assistance.", revision_no = "15", abstract = "Adaptive Alkylation: Palladium-catalyzed asymmetric alkylation enables access to fully substituted enantioenriched oxygenated stereocenters, which can be transformed easily to α-hydroxyketones, esters, and acids, providing a catalytic, enantioselective synthesis for natural products.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74342, title ="Palladium-Catalyzed Enantioselective Oxidation of Chiral Secondary Alcohols: Access to Both Enantiomeric Series", author = "Ebner, David C. and Trend, Raissa M.", journal = "Angewandte Chemie International Edition", volume = "47", number = "34", pages = "6367-6370", month = "August", year = "2008", doi = "10.1002/anie.200801865", issn = "14337851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-152617371", note = "© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nReceived: April 22, 2008; Published online: July 14, 2008. \n\nWe are grateful to the NIH-NIGMS (R01 GM65961-01), NSF (predoctoral fellowship to D.C.E.), NDSEG (predoctoral fellowship to D.C.E.), Bristol-Myers Squibb and the American Chemical Society (predoctoral fellowship to R.M.T.), EPSRC, and EU.", revision_no = "21", abstract = "Rapid resolution: A new catalyst system for the oxidative kinetic resolution of secondary alcohols leads to dramatic rate increases. This system allows the use of a diamine to provide access to either enantiomer of a range of alcohols with good selectivity factors (see scheme). This method has been applied to the formal total synthesis of (−)-amurensinine.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74393, title ="The total synthesis of (-)-cyanthiwigin F by means of double catalytic enantioselective alkylation", author = "Enquist, John A., Jr. and Stoltz, Brian M.", journal = "Nature", volume = "453", number = "7199", pages = "1228-1231", month = "June", year = "2008", doi = "10.1038/nature07046", issn = "0028-0836", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170216-150759253", note = "© 2008 Macmillan Publishers Limited. \n\nReceived 26 November 2007; accepted 2 May 2008. \n\nThe authors wish to thank NIH-NIGMS (R01GM080269-01), Amgen, Abbott, Boehringer Ingelheim, Merck and Bristol-Myers Squibb for financial support. We also wish to thank M. W. Day and L. M. Henling for X-ray crystallographic expertise, S. Virgil, A. Harned, D. White, D. Caspi and J. T. Mohr for helpful discussions, and M. T. Hamann for an authentic sample and spectra of cyanthiwigin F. We thank E. J. Corey for guidance and mentorship, on the occasion of his 80th birthday. \n\nCrystallographic data have been deposited at the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK, and copies can be obtained on request, free of charge, by quoting the publication citation and the deposition number 664430.", revision_no = "18", abstract = "Double catalytic enantioselective transformations are powerful synthetic methods that can facilitate the construction of stereochemically complex molecules in a single operation. In addition to generating two or more stereocentres in a single reaction, multiple asymmetric reactions also impart increased enantiomeric excess to the final product in comparison with the analogous single transformation. Furthermore, multiple asymmetric operations have the potential to independently construct several stereocentres at remote points within the same molecular scaffold, rather than relying on pre-existing chiral centres that are proximal to the reactive site. Despite the inherent benefits of multiple catalytic enantioselective reactions, their application to natural product total synthesis remains largely underutilized. Here we report the use of a double stereoablative enantioselective alkylation reaction in a concise synthesis of the marine diterpenoid (-)-cyanthiwigin F (ref. 8). By employing a technique for independent, selective formation of two stereocentres in a single stereoconvergent operation, we demonstrate that a complicated mixture of racemic and meso diastereomers may be smoothly converted to a synthetically useful intermediate with exceptional enantiomeric excess. The stereochemical information generated by means of this catalytic transformation facilitates the easy and rapid completion of the total synthesis of this marine natural product.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/72290, title ="C–H bond functionalizations with palladium(II): intramolecular oxidative annulations of arenes", author = "Ferreira, Eric M. and Zhang, Haiming", journal = "Tetrahedron", volume = "64", number = "26", pages = "5987-6001", month = "June", year = "2008", doi = "10.1016/j.tet.2008.01.052", issn = "0040-4020", url = "https://resolver.caltech.edu/CaltechAUTHORS:20161128-075820774", note = "© 2008 Elsevier Ltd. \n\nReceived 24 August 2007, Revised 13 October 2007, Accepted 15 October 2008, Available online 16 January 2008. \n\nThe authors wish to thank the NIH-NIGMS (R01 GM65961-01), Bristol–Myers Squibb Company (graduate fellowship to E.M.F.), the NSF (graduate fellowship to E.M.F.), the Dreyfus Foundation, Merck Research Laboratories, Research Corporation, Abbott Laboratories, Pfizer, Amgen, GlaxoSmithKline, Lilly, Boehringer Ingelheim, and Johnson and Johnson for generous financial support.", revision_no = "14", abstract = "Oxidative annulations for the synthesis of carbocycles were developed using a catalytic palladium(II) system. Indoles with pendant olefin tethers were oxidatively cyclized to form annulated products. Electron-rich aromatic systems were also investigated, culminating in the synthesis of benzofurans and dihydrobenzofurans by a similar protocol. These reactions were demonstrated to proceed by an initial C–H bond functionalization event, followed by olefin insertion and β-hydride elimination.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74444, title ="Homogeneous Pd-Catalyzed Enantioselective Decarboxylative Protonation", author = "Marinescu, Smaranda C. and Nishimata, Toyoki", journal = "Organic Letters", volume = "10", number = "6", pages = "1039-1042", month = "March", year = "2008", doi = "10.1021/ol702821j", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170221-162726154", note = "© 2008 American Chemical Society. \n\nReceived November 21, 2007. Publication Date (Web): February 28, 2008. \n\nWe thank Sankyo Co., Ltd. (financial support of T.N.), Eli Lilly (predoctoral fellowship to J.T.M.), Amgen, and Bristol-Myers Squibb for generous funding.", revision_no = "18", abstract = "General homogeneous conditions for the palladium-catalyzed synthesis of carbonyl compounds with tertiary carbon stereocenters at the α-position are reported. The highly reactive catalyst tolerates a variety of substrate substitution and functionality, and generates enantioenriched cyclic ketones from racemic allyl β-ketoester starting materials.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74339, title ="The Biology and Chemistry of the Zoanthamine Alkaloids", author = "Behenna, Douglas C. and Stockdill, Jennifer L.", journal = "Angewandte Chemie International Edition", volume = "47", number = "13", pages = "2365-2386", month = "March", year = "2008", doi = "10.1002/anie.200703172", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-151808188", note = "© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nReceived: July 16, 2007; Published online: February 28, 2007. \n\nWe thank www.zoaid.com for the use of pictures of zoanthids throughout this Review, and Teresa Barth for assistance with the design of the graphics and frontispiece.", revision_no = "10", abstract = "Marine natural products have long played an important role in natural products chemistry and drug discovery. Mirroring the rich variety and complicated interactions of the marine environment, the substances isolated from sea creatures tend to be incredibly diverse in both molecular structure and biological activity. The natural products isolated from the polyps of marine zoanthids are no exception. The zoanthamine alkaloids, the first of which were isolated over 20 years ago, are of particular interest to the synthetic community because they feature a novel structural framework and exhibit a broad range of biological activities. In this Review, we summarize the major contributions to understanding the zoanthamine natural products with regard to their isolation and structure determination, as well as studies on their biological activity and total synthesis.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74512, title ="Orthogonal Synthesis of Indolines and Isoquinolines via Aryne Annulation", author = "Gilmore, Christopher D. and Allan, Kevin M.", journal = "Journal of the American Chemical Society", volume = "130", number = "5", pages = "1558-1559", month = "February", year = "2008", doi = "10.1021/ja0780582", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170223-153451419", note = "© 2008 American Chemical Society. \n\nReceived 21 October 2007. Published online 15 January 2008. Published in print 1 February 2008. \n\nThe authors thank Abbott, Amgen, Bristol-Myers Squibb, Merck, and Caltech for generous funding.", revision_no = "13", abstract = "Described in this report is the development of two unique methodologies exploiting the reactivity of arynes. Reaction of N-carbamoyl-functionalized enamine derivatives with benzyne affords substituted indolines. An orthogonal reactivity is uncovered when related enamine derivatives are modified as amides, such that isoquinolines are formed as the product of condensation with benzyne. This latter transformation is applied to a concise total synthesis of the opiate alkaloid papaverine.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74453, title ="The Catalytic Asymmetric Total Synthesis of Elatol", author = "White, David E. and Stewart, Ian C.", journal = "Journal of the American Chemical Society", volume = "130", number = "3", pages = "810-811", month = "January", year = "2008", doi = "10.1021/ja710294k", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-082042531", note = "© 2008 American Chemical Society. \n\nReceived 13 November 2007. Published online 29 December 2007. Published in print 1 January 2008. \n\nWe thank the NIH-NIGMS (R01 GM080269-01, R01 GM31332-05, postdoctoral fellowships to D.E.W. and I.C.S.), Abbott, Amgen, Bristol-Myers Squibb, Merck, and Caltech for generous funding; Materia, Inc. for their kind donation of catalyst 22 used in these studies; Professors Mercedes Cueto and Karen L. Erickson for their kind donation of natural samples of elatol (1); Brinton Seashore-Ludlow for experimental assistance; and Professor Peter B. Dervan and David M. Chenoweth for use of their HPLC.", revision_no = "18", abstract = "Described in this report is the first total synthesis of elatol, a halogenated sesquiterpene in the chamigrene natural product family. The key disconnections in our synthetic approach include an enantioselective decarboxylative allylation to form the all-carbon quaternary stereocenter and a ring-closing olefin metathesis to concomitantly form the spirocyclic core as well as the fully substituted chlorinated olefin. This strategy represents a general platform for accessing the chamigrene natural product family, as demonstrated by the synthesis of (+)-laurencenone B as an intermediate in our route.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74462, title ="Progress toward the Synthesis of the Basiliolides and Transtaganolides: An Intramolecular Pyrone Diels−Alder Entry into a Novel Class of Natural Products", author = "Nelson, Hosea M. and Stoltz, Brian M.", journal = "Organic Letters", volume = "10", number = "1", pages = "25-28", month = "January", year = "2008", doi = "10.1021/ol702501s", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-094911569", note = "© 2008 American Chemical Society. \n\nReceived 12 October 2007. Published online 7 December 2007. Published in print 1 January 2008. \n\nWe thank the Ford Foundation (predoctoral fellowship to H.M.N.), Abbott, Amgen, Bristol-Myers Squibb, Merck, Boehringer Ingelheim, and Caltech for generous funding.", revision_no = "13", abstract = "Efforts directed toward the synthesis of a basiliolide/transtaganolide model system are disclosed. A highly endo-selective intramolecular pyrone Diels−Alder (IMPDA) cycloaddition rapidly constructs the tricyclic core of the basiliolides and transtaganolides.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74327, title ="Enantioselective Tsuji Allylations", author = "Mohr, Justin T. and Stoltz, Brian M.", journal = "Chemistry – An Asian Journal", volume = "2", number = "12", pages = "1476-1491", month = "December", year = "2007", doi = "10.1002/asia.200700183", issn = "1861-4728", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-130857215", note = "© 2007 John Wiley & Sons, Inc. \n\nManuscript Received: 31 May 2007. Version of record online: 12 October 2007. Issue online: 27 November 2007. \n\nWe dedicate this focus review to Prof. Jiro Tsuji on the occasion of his 80th birthday. We thank Eli Lilly (predoctoral fellowship to JTM) and Caltech for financial support, Douglas C. Behenna for helpful conversations, and Masaki Seto for translating the abstract into Japanese. \n\nWe thank NIH-NIGMS (R01 GM 080269-01), Eli Lilly (predoctoral fellowship to J.T.M.), and Caltech for financial support, Douglas C. Behenna for helpful conversations, and Masaki Seto for translating the abstract into Japanese.", revision_no = "13", abstract = "The family of allylation reactions developed by Tsuji in the 1980s are capable of generating tertiary and quaternary carbon stereocenters from several synthetic precursors. Despite the utility of these transformations, they have seen little use in the synthesis of natural products. Recently, the power of these reactions was significantly enhanced by the development of enantioselective versions of these transformations. Applications of these methods to the enantioselective syntheses of natural products and pharmaceutical compounds highlight the importance of these developments.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74485, title ="Catalytic enantioselective stereoablative reactions: an unexploited approach to enantioselective catalysis", author = "Mohr, Justin T. and Ebner, David C.", journal = "Organic and Biomolecular Chemistry", volume = "5", number = "22", pages = "3571-3576", month = "November", year = "2007", doi = "10.1039/B711159M", issn = "1477-0520", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170223-071515692", note = "© 2007 The Royal Society of Chemistry. \n\nReceived 20 Jul 2007, Accepted 30 Aug 2007. First published online 01 Oct 2007. \n\nWe thank NIH-NIGMS (R01 GM 080269-01), Eli Lilly (predoctoral fellowship to JTM), NDSEG (predoctoral fellowship to DCE), and NSF (predoctoral fellowship to DCE) for funding.", revision_no = "13", abstract = "Approaches to the preparation of enantioenriched materials via catalytic methods that destroy stereogenic elements of a molecule are discussed. Although these processes often decrease overall molecular complexity, there are several notable advantages including material recycling, enantiodivergence and convergence, and increased substrate scope. Examples are accompanied by discussion of the critical design elements required for the success of these methods.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74449, title ="The Inner-Sphere Process in the Enantioselective Tsuji Allylation Reaction with (S)-t-Bu-phosphinooxazoline Ligands", author = "Keith, John A. and Behenna, Douglas C.", journal = "Journal of the American Chemical Society", volume = "129", number = "39", pages = "11876-11877", month = "October", year = "2007", doi = "10.1021/ja070516j", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-080249889", note = "© 2007 American Chemical Society. \n\nReceived 26 January 2007. Published online 8 September 2007. \nPublished in print 1 October 2007. \n\nWe thank K. Tani, A. Harned, J. Enquist, and N. Sherden for experimental collaboration and discussion, and M. Day and L. Henling for crystallography assistance. J.A.K. thanks R. (Smith) Nielsen for discussions. This research was partly funded by Chevron-Texaco, and the facilities used were funded by grants from ARO-DURIP, ONR-DURIP, IBM-SUR, Fannie and John Hertz Foundation (D.C.B.), and Eli Lilly (J.T.M.) with additional support from NSF (CTS-0608889, WAG) and NIH-NIGMS (R01GM080269-01, BMS).", revision_no = "14", abstract = "We propose an inner-sphere mechanism explaining the unique performance of the Tsuji asymmetrical allylation reaction using hard prochiral enolate nucleophiles and non-prochiral allyl groups. Using first principles quantum mechanics (B3LYP density functional theory), we find that the pathway for this reaction involves nucleophilic attack followed by interconversion from a five-coordinate Pd complex to a four-coordinate complex. This intermediate is trapped in a potential well and escapes via reductive elimination that proceeds through a seven-membered transition state to generate the product and a Pd^0 complex. This seven-membered transition state contrasts dramatically from the usual three-centered C−C reductive elimination paradigm generally associated with C−C coupling reactions. This inner-sphere asymmetric allylation pathway involving hard enolates is energetically more favorable than outer-sphere nucleophilic attack, a process understood to occur in asymmetric allylic alkylations with soft enolates.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74349, title ="Convergency and Divergency as Strategic Elements in Total Synthesis: The Total Synthesis of (−)-Drupacine and the Formal Total Synthesis of (±)-Cephalotaxine, (−)-Cephalotaxine, and (+)-Cephalotaxine", author = "Liu, Qi and Ferreira, Eric M.", journal = "Journal of Organic Chemistry", volume = "72", number = "19", pages = "7352-7358", month = "September", year = "2007", doi = "10.1021/jo0710883", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-155814896", note = "© 2007 American Chemical Society. \n\nReceived June 8, 2007; Publication Date (Web): August 18, 2007. \n\nWe thank the NIH-NIGMS (R01 GM65961-01), Bristol-Myers Squibb Co. (graduate fellowship to E.M.F.), the NSF (graduate fellowship to E.M.F.), the Dreyfus Foundation, Merck Research Laboratories, Research Corporation, Abbott Laboratories, Pfizer, Amgen, GlaxoSmithKline, Lilly, and Johnson and Johnson for generous financial support. We are grateful to Ernie Cruz, Sandy Ma, and John Enquist for experimental assistance.", revision_no = "16", abstract = "A concise route toward the syntheses of (−)-drupacine and (+)- and (−)-cephalotaxine has been developed. The syntheses rely on Pd(II)-catalyzed aerobic oxidative heterocyclization chemistry, which was employed to rapidly construct an important spirocyclic amine intermediate. A dynamic β-elimination/conjugate addition process was strategically applied to complete the first asymmetric total synthesis of (−)-drupacine. ", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74475, title ="A Facile and Modular Synthesis of Phosphinooxazoline Ligands", author = "Tani, Kousuke and Behenna, Douglas C.", journal = "Organic Letters", volume = "9", number = "13", pages = "2529-2531", month = "June", year = "2007", doi = "10.1021/ol070884s", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-151224179", note = "© 2007 American Chemical Society. \n\nReceived 16 April 2007. Published online 31 May 2007. Published in print 1 June 2007. \n\nThe authors gratefully acknowledge Ono Pharmaceutical Co., Ltd. (postdoctoral fellowship to K.T.), The Fannie and John Hertz Foundation (predoctoral fellowship to D.C.B.), Eli Lilly and Co. (predoctoral funding to R.M.M.), California Institute of Technology, and Abbott, Amgen, Bristol-Myers Squibb, and Merck for financial support.", revision_no = "13", abstract = "The copper(I) iodide catalyzed phosphine/aryl halide coupling procedure of Buchwald et al. provides modular, robust, and scaleable access to phosphinooxazoline (PHOX) ligands. The advantages of this method are highlighted by the convenient synthesis of PHOX ligands with varied steric and electronic properties, which would be challenging to synthesize by other protocols.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74341, title ="Synthesis of the Carbocyclic Core of Zoanthenol: Implementation of an Unusual Acid-Catalyzed Cyclization", author = "Behenna, Douglas C. and Stockdill, Jennifer L.", journal = "Angewandte Chemie International Edition", volume = "46", number = "22", pages = "4077-4080", month = "May", year = "2007", doi = "10.1002/anie.200700430", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-152142036", note = "© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nReceived: January 31, 2007; Published online: April 19, 2007. \n\nThe authors wish to thank the Fannie and John Hertz Foundation (predoctoral fellowship to D.C.B), Novartis (predoctoral fellowship to J.L.S.), Merck, Pfizer, and Lilly for financial support.", revision_no = "10", abstract = "A smokin' hot cyclization! When the racemic cyclization precursor is heated in neat trifluoroacetic acid, an unusual Friedel–Crafts-type cyclization forms the carbocyclic core of the marine alkaloid zoanthenol containing two all-carbon-substituted quaternary centers. Catalytic asymmetric alkylation allows entry into an enantioselective route.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74456, title ="Synthesis of 2-Quinuclidonium by Eliminating Water: Experimental Quantification of the High Basicity of Extremely Twisted Amides", author = "Ly, Tony and Krout, Michael", journal = "Journal of the American Chemical Society", volume = "129", number = "7", pages = "1864-1865", month = "February", year = "2007", doi = "10.1021/ja067703m", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-084852047", note = "© 2007 American Chemical Society. \n\nReceived 27 October 2006. Published online 27 January 2007. Published in print 1 February 2007. \n\nWe acknowledge funding from the University of California, Riverside, Ono Pharmaceutical Co. Ltd (for a postdoctoral fellowship to K.T.), and Bristol-Myers Squibb. D.K.P. thanks the Kenan Trust and the NSF REU Site in Bioanalytical Science supported by Grant CHE-0552493.", revision_no = "13", abstract = "The chemical properties of an extremely twisted amide are examined quantitatively for the first time. The predicted high basicity of 2-quinuclidonium is confirmed experimentally by measuring the gas-phase proton affinity using the extended kinetic method. Fragmentation of this molecule further reveals that the lack of resonance stabilization weakens the amide bond. Furthermore, a new route for synthesizing 2-quinuclidonium by eliminating water is demonstrated in the gas phase.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/72291, title ="The synthesis of C-3β functionalized indoles via a hydroboration/Suzuki–Miyaura coupling sequence", author = "Ferreira, Eric M. and Stoltz, Brian M.", journal = "Tetrahedron Letters", volume = "47", number = "48", pages = "8579-8582", month = "November", year = "2006", doi = "10.1016/j.tetlet.2006.09.112", issn = "0040-4039", url = "https://resolver.caltech.edu/CaltechAUTHORS:20161128-080903512", note = "© 2006 Elsevier Ltd. \n\nReceived 1 September 2006, Accepted 21 September 2006, Available online 13 October 2006. \n\nThe authors wish to thank the NIH-NIGMS (R01 GM65961-01), Bristol-Myers Squibb Company (graduate fellowship to E.M.F.), the NSF (graduate fellowship to E.M.F.), the Dreyfus Foundation, Merck Research Laboratories, Research Corporation, Abbott Laboratories, Pfizer, Amgen, GlaxoSmithKline, Lilly, and Johnson and Johnson for their generous financial support.", revision_no = "15", abstract = "A method for the functionalization of C-3β of vinyl indoles is described. The procedure involves a hydroboration, followed by a Suzuki–Miyaura cross-coupling with the intermediate alkyl borane. Triflates, bromides, and iodides are suitable coupling partners, allowing access to a variety of elaborated indole compounds.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74508, title ="Convergent and Diastereoselective Synthesis of the Polycyclic Pyran Core of Saudin", author = "Tambar, Uttam K. and Kano, Taichi", journal = "Journal of Organic Chemistry", volume = "71", number = "22", pages = "8357-8364", month = "October", year = "2006", doi = "10.1021/jo061236+", issn = "0022-3263", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170223-142410037", note = "© 2006 American Chemical Society. \n\nReceived 15 June 2006. Published online 4 October 2006. Published in print 1 October 2006. \n\nThe authors are grateful to the California Institute of Technology, NSF-PECASE, NDSEG (graduate fellowship to U.K.T.), the Japan Society for the Promotion of Science (postdoctoral fellowship to T.K.), Bristol-Myers Squibb, Merck, Abbott, Amgen, Lilly, Pfizer, and GlaxoSmithKline for generous financial support. Dr. John H. Phillips and Mr. Galen Loram are acknowledged for experimental assistance. We thank Mr. Larry M. Henling and Dr. Michael W. Day for X-ray crystallographic expertise.", revision_no = "22", abstract = "The natural product saudin was found to induce hypoglycemia in mice and, therefore, could be an appealing lead structure for the development of new agents to treat diabetes. A diastereoselective tandem Stille-oxa-electrocyclization reaction has been developed which provides access to the core structure of saudin in a rapid and convergent manner. This new reaction has been extended to the convergent preparation of a series of polycyclic pyran systems. Progress has been made on the advancement of these complex pyran systems toward the natural product. A complete account of these synthetic efforts is presented.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/4941, title ="A unified synthetic approach to the pyrazinone dragmacidins", author = "Garg, Neil K. and Stoltz, Brian M.", journal = "Chemical Communications", volume = "2006", number = "36", pages = "3769-3779", month = "September", year = "2006", doi = "10.1039/b605929e", issn = "1359-7345", url = "https://resolver.caltech.edu/CaltechAUTHORS:GARcc06", note = "© Royal Society of Chemistry 2006. \n\nReceived (in Cambridge, UK) 26th April 2006, Accepted 15th June 2006. First published on the web 18th July 2006. Feature article \n\nRichmond Sarpong and Daniel Caspi are gratefully acknowledged for their outstanding contributions to the dragmacidin project. The authors thank the NIH-NIGMS (R01 GM65961-01), the NDSEG (predoctoral fellowship to N.K.G.), AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Pfizer, Merck, Amgen, Research Corporation, Roche and GlaxoSmithKline for generous funding.", revision_no = "16", abstract = "This review describes recent developments from our laboratory involving the synthesis of the structurally complex, pyrazinone-containing dragmacidin alkaloids.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74438, title ="A Convergent and Enantioselective Synthesis of (+)-Amurensinine via Selective C−H and C−C Bond Insertion Reactions", author = "Tambar, Uttam K. and Ebner, David C.", journal = "Journal of the American Chemical Society", volume = "128", number = "36", pages = "11752-11753", month = "September", year = "2006", doi = "10.1021/ja0651815", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170221-152140812", note = "© 2006 American Chemical Society. \n\nReceived 20 July 2006. Published online 17 August 2006. Published in print 1 September 2006. \n\nThe authors are grateful to the NIH-NIGMS (R01 GM65961-01), NDSEG (predoctoral fellowships to U.K.T. and D.C.E.), NSF (predoctoral fellowship to D.C.E.), A. P. Sloan Foundation, Research Corporation, Bristol-Myers Squibb, Amgen, Merck, Pfizer, Novartis, Lilly, Roche, Abbott, AstraZeneca, and Caltech for financial support.", revision_no = "16", abstract = "A convergent and enantioselective synthesis of the natural product amurensinine is described. The synthetic strategy takes advantage of mild and selective C−H and C−C bond insertion reactions, in addition to the palladium-catalyzed aerobic oxidative kinetic resolution recently developed in these laboratories.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74447, title ="Catalytic Enantioselective Decarboxylative Protonation", author = "Mohr, Justin T. and Nishimata, Toyoki", journal = "Journal of the American Chemical Society", volume = "128", number = "35", pages = "11348-11349", month = "September", year = "2006", doi = "10.1021/ja063335a", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-073849342", note = "© 2006 American Chemical Society. \n\nReceived 17 May 2006. Published online 15 August 2006. Published in print 1 September 2006. \n\nThe authors thank Eli Lilly (predoctoral fellowship to J.T.M.), Sankyo Co., Ltd. (financial support of T.N.), The Fannie and John Hertz Foundation (predoctoral fellowship to D.C.B.), Merck, Amgen, Johnson & Johnson, Bristol-Myers Squibb, and the Dreyfus Foundation for generous funding.", revision_no = "12", abstract = "We report a highly enantioselective, general catalytic system for the facile synthesis of tertiary stereocenters by protonation adjacent to cyclic ketones. The method relies on catalytic decarboxylative protonation of readily accessible racemic quaternary β-ketoesters. A range of substituted cycloalkanone compounds can be accessed through this process with high levels of enantioselectivity.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74448, title ="The Catalytic Enantioselective, Protecting Group-Free Total Synthesis of (+)-Dichroanone", author = "McFadden, Ryan M. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "128", number = "24", pages = "7738-7739", month = "June", year = "2006", doi = "10.1021/ja061853f", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-075015251", note = "© 2006 American Chemical Society. \n\nReceived 17 March 2006. Published online 26 May 2006. Published in print 1 June 2006. \n\nWe are grateful to Eli Lilly (graduate fellowship to R.M.M.), Johnson & Johnson, Bristol-Myers Squibb, Merck, Amgen, and the Dreyfus Foundation for generous funding. Doug Behenna, J. T. Mohr, and Dr. Andrew Harned are acknowledged for helpful discussions.", revision_no = "14", abstract = "Herein we report the first enantioselective total synthesis of (+)-dichroanone, confirming the absolute configuration of the natural product. This protecting group-free route features the first application of our enantioselective Tsuji allylation in the context of a natural product total synthesis. Additionally, this 11-step preparation of the molecule from commercial material features a novel Kumada-aromatization strategy and a rapid sequence for the conversion of a phenol to a hydroxy-p-benzoquinone.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/55925, title ="Synthesis and structural analysis of 2-quinuclidonium tetrafluoroborate", author = "Tani, Kousuke and Stoltz, Brian M.", journal = "Nature", volume = "441", number = "7094", pages = "731-734", month = "June", year = "2006", doi = "10.1038/nature04842", issn = "0028-0836", url = "https://resolver.caltech.edu/CaltechAUTHORS:20150319-100435030", note = "© 2006 Nature Publishing Group.\n\nReceived 21 March 2006; Accepted 26 April 2006.\n\nWe thank H. H. Wasserman, E. J. Corey, and N. J. Leonard for discussions. We thank Ono Pharmaceutical Co. Ltd (for a postdoctoral fellowship to K.T.), the Research Corporation, the Camille and Henry Dreyfus Foundation, Merck, Pfizer, Lilly, Amgen and Bristol-Myers Squibb for financial support. We also thank M. W. Day and L. M. Henling for their X-ray crystallographic expertise.", revision_no = "15", abstract = "The amide functional group is one of the most fundamental motifs found in chemistry and biology, and it has been studied extensively for the past century. Typical acyclic amides are planar. But the amide groups of bicyclic bridgehead lactams are highly twisted, and this distortion from planarity can dramatically affect the stability and reactivity of these amides; it also increases the basicity of the nitrogen so that it often behaves more like an amine than a typical planar amide. As a result, the structures and reactivity profiles of these 'anti-Bredt' amides differ significantly from those of planar amides. It is possible that this twisting phenomenon is not exclusive to cyclic systems—non-planarity may also be a critical biological design element that leads to amide ground-state destabilization and alters the reactivity, selectivity and mechanism of various protein and enzymatic processes (such as amide hydrolysis). The intriguing qualities of these twisted amides were first recognized in 1938 (ref. 11), wherein one of the simplest families was introduced—molecules containing the 1-azabicyclo[2.2.2]octan-2-one system. But the parent member of this group, 2-quinuclidone (molecule 1 in this paper), has not yet been unambiguously synthesized. Here, we report the chemical synthesis, isolation and full characterization of the HBF_4 salt of 1. Critical to the success of the synthesis and isolation was the decision to generate 1 by a route other than classical amide bond formation. We anticipate that these results will provide a greater understanding of the properties of amide bonds.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/3509, title ="2-Diazoacetoacetic acid, an efficient and convenient reagent for the synthesis of alpha-diazo-beta-ketoesters", author = "Meyer, Michael E. and Ferreira, Eric M.", journal = "Chemical Communications", volume = "2006", number = "12", pages = "1316-1318", month = "March", year = "2006", doi = "10.1039/b517719g", issn = "1359-7345", url = "https://resolver.caltech.edu/CaltechAUTHORS:MEYcc06", note = "© The Royal Society of Chemistry 2006 \n\nReceived (in Bloomington, IN, USA) 13th December 2005, Accepted 27th January 2006. First published on the web 15th February 2006 \n\nThe authors gratefully acknowledge the NSF (predoctoral fellowship for E.M.F.), Bristol-Myers Squibb (Graduate Fellowship in Synthetic Organic Chemistry to E.M.F.), AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Pfizer, Merck, Amgen, Research Corporation, Roche, the Dreyfus Foundation, and GlaxoSmithKline for generous funding. \n\nElectronic supplementary information (ESI) available: experimental details and characterization data for all compounds. See DOI: 10.1039/b517719g", revision_no = "16", abstract = "The formation of various alpha-diazo acetoacetic esters can be obtained in a single transformation with good to excellent yields using readily available 2-diazoacetoacetic acid.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74497, title ="Effects of a Modified Dye-Labeled Nucleotide Spacer Arm on Incorporation by Thermophilic DNA Polymerases", author = "Lacenere, Christopher J. and Garg, Neil K.", journal = "Nucleosides, Nucleotides and Nucleic Acids", volume = "25", number = "1", pages = "9-15", month = "January", year = "2006", doi = "10.1080/15257770500377714", issn = "1525-7770", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170223-112338543", note = "© 2006 Taylor & Francis Group, LLC. \n\nReceived 19 February 2005; accepted 26 May 2005. \n\nThis work was supported in part by DARPA, the National Institutes of Health, and the Rosen fellowship. The authors would like to thank Peter Dervan and his group for the use of their imager. C. L. thanks John DeModena and Saurabh Vyawahare for their useful advice and comments.\n", revision_no = "11", abstract = "The ability of eight commercially available thermophilic DNA polymerases to sequentially incorporate fluorescently labeled nucleotides sequentially was analyzed by a gel based primer extension assay. Cy5-dUTP or a variant nucleotide in which the linker had been lengthened by 14 atoms between the dye and the nucleobase were compared. We found that the Cy5-dUTP with a longer linker resulted in longer primer extension lengths. Furthermore, some of the assayed polymerases are capable of extending the primer to the full or near full length of 30 nucleotides using dye-labeled nucleotides exclusively.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74395, title ="Oxidative Cyclizations in a Nonpolar Solvent Using Molecular Oxygen and Studies on the Stereochemistry of Oxypalladation", author = "Trend, Raissa M. and Ramtohul, Yeeman K.", journal = "Journal of the American Chemical Society", volume = "127", number = "50", pages = "17778-17788", month = "December", year = "2005", doi = "10.1021/ja055534k", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170216-152155230", note = "© 2005 American Chemical Society. \n\nReceived August 12, 2005; Publication Date (Web): November 15, 2005. \n\nThe authors wish to thank the NIH-NIGMS (R01 GM65961-01), Bristol-Myers Squibb Company and the American Chemical Society (graduate fellowship to R.M.T.), the University of California TRDRP (postdoctoral fellowship to Y.K.R.), the Dreyfus Foundation, Merck Research Laboratories, Research Corporation, Abbott Laboratories, Pfizer, Amgen, GlaxoSmithKline, Lilly, and Johnson and Johnson for generous financial support. Drs. Eric Ferreira, Jonathan Owen, and Andrew Waltman are acknowledged for helpful discussions.", revision_no = "16", abstract = "Oxidative cyclizations of a variety of heteroatom nucleophiles onto unactivated olefins are catalyzed by palladium(II) and pyridine in the presence of molecular oxygen as the sole stoichiometric oxidant in a nonpolar solvent (toluene). Reactivity studies of a number of N-ligated palladium complexes show that chelating ligands slow the reaction. Nearly identical conditions are applicable to five different types of nucleophiles:\u2009 phenols, primary alcohols, carboxylic acids, a vinylogous acid, and amides. Electron-rich phenols are excellent substrates, and multiple olefin substitution patterns are tolerated. Primary alcohols undergo oxidative cyclization without significant oxidation to the aldehyde, a fact that illustrates the range of reactivity available from various Pd(II) salts under differing conditions. Alcohols can form both fused and spirocyclic ring systems, depending on the position of the olefin relative to the tethered alcohol; the same is true of the acid derivatives. The racemic conditions served as a platform for the development of an enantioselective reaction. Experiments with stereospecifically deuterated primary alcohol substrates rule out a “Wacker-type” mechanism involving anti oxypalladation and suggest that the reaction proceeds by syn oxypalladation for both mono- and bidentate ligands. In contrast, cyclizations of deuterium-labeled carboxylic acid substrates undergo anti oxypalladation.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74345, title ="Deracemization of Quaternary Stereocenters by Pd-Catalyzed Enantioconvergent Decarboxylative Allylation of Racemic β-Ketoesters", author = "Mohr, Justin T. and Behenna, Douglas C.", journal = "Angewandte Chemie International Edition", volume = "44", number = "42", pages = "6924-6927", month = "October", year = "2005", doi = "10.1002/anie.200502018", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-153759053", note = "© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nReceived: June 11, 2005; Published online: October 5, 2005. \n\nThe authors wish to thank the Fannie and John Hertz Foundation (predoctoral fellowship to D.C.B.), the NIH (postdoctoral fellowship to A.M.H.), Research Corporation, the Camille and Henry Dreyfus Foundation, Merck, Pfizer, and Lilly for financial support, and Prof. D. A. Dougherty for helpful discussions.", revision_no = "12", abstract = "Stereochemical alchemy! Racemic allyl β-ketoesters allow the regiocontrolled formation of enolates, where the same catalyst is intimately involved in both the stereoablative (C-C bond-breaking) and stereoselective (C-C bond-forming) steps. This mechanistic and practical insight led to the formation of multiple quaternary carbon stereocenters in a single cascade reaction (see scheme).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74474, title ="Heterogeneous Reductive Isomerization Reaction Using Catalytic Pd/C and H_2", author = "Caspi, Daniel D. and Garg, Neil K.", journal = "Organic Letters", volume = "7", number = "12", pages = "2513-2516", month = "June", year = "2005", doi = "10.1021/ol050952f", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-150113004", note = "© 2005 American Chemical Society. \n\nReceived 28 April 2005. Published online 14 May 2005. Published in print 1 June 2005. \n\nThe authors gratefully acknowledge the NIH-NIGMS (R01 GM65961-01), the NDSEG (predoctoral fellowship to N.K.G.), Eli Lilly (predoctoral fellowship to D.D.C.), AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Pfizer, Merck, Amgen, Research Corporation, Roche, and GlaxoSmithKline for generous funding.", revision_no = "16", abstract = "A highly selective catalytic reductive isomerization reaction is described. The extremely mild and neutral reaction conditions (10% Pd/C, H_2, and MeOH at 0 °C) tolerate a wide range of functional groups and generally result in excellent yields. Mechanistic studies suggest that this reaction does not proceed via a stepwise reduction/elimination sequence or a π-allylpalladium intermediate.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74471, title ="Progress toward the Total Synthesis of Saudin: Development of a Tandem Stille-Oxa-Electrocyclization Reaction", author = "Tambar, Uttam K. and Kano, Taichi", journal = "Organic Letters", volume = "7", number = "12", pages = "2413-2416", month = "June", year = "2005", doi = "10.1021/ol050705b", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-144318676", note = "© 2005 American Chemical Society. \n\nReceived 1 April 2005. Published online 13 May 2005. Published in print 1 June 2005. \n\nWe are grateful to the California Institute of Technology, NSF-PECASE, and NDSEG (graduate fellowship to U.K.T.) for generous financial support and John F. Zepernick for experimental assistance. We thank Mr. Larry M. Henling and Dr. Michael W. Day for X-ray crystallographic expertise.", revision_no = "12", abstract = "A diastereoselective tandem Stille-oxa-electrocyclization reaction provides access to the core of the diterpenoid natural product saudin. Additionally, this new reaction sequence was extended to the convergent preparation of related polycyclic pyran systems.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74461, title ="Development of an Enantiodivergent Strategy for the Total Synthesis of (+)- and (−)-Dragmacidin F from a Single Enantiomer of Quinic Acid", author = "Garg, Neil K. and Caspi, Daniel D.", journal = "Journal of the American Chemical Society", volume = "127", number = "16", pages = "5970-5978", month = "April", year = "2005", doi = "10.1021/ja050586v", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-093427303", note = "© 2005 American Chemical Society. \n\nReceived 28 January 2005. Published online 2 April 2005. Published in print 1 April 2005. \n\nThe authors thank the NIH-NIGMS (Grant R01 GM65961-01), the NDSEG (predoctoral fellowship to N.K.G.), Eli Lilly (predoctoral fellowship to D.D.C.), AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Pfizer, Merck, Amgen, Research Corp., Roche, and GlaxoSmithKline for generous funding. Drs. R. Riccio and A. Casapullo are acknowledged for an authentic sample of (−)-dragmacidin F. We also thank the Dervan and MacMillan laboratories for helpful discussions and the use of instrumentation.", revision_no = "15", abstract = "An enantiodivergent strategy for the total chemical synthesis of both (+)- and (−)-dragmacidin F beginning from a single enantiomer of quinic acid has been developed and successfully implemented. Although unique, the synthetic routes to these antipodes share a number of key features, including novel reductive isomerization reactions, Pd(II)-mediated oxidative carbocyclization reactions, halogen-selective Suzuki couplings, and high-yielding late-stage Neber rearrangements.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74457, title ="The Direct Acyl-Alkylation of Arynes", author = "Tambar, Uttam K. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "127", number = "15", pages = "5340-5341", month = "April", year = "2005", doi = "10.1021/ja050859m", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-085357234", note = "© 2005 American Chemical Society. \n\nReceived 9 February 2005. Published online 26 March 2005. Published in print 1 April 2005. \n\nThis work is dedicated to our friend and colleague Professor John D. Roberts, the father of benzyne.8 We are grateful to the NDSEG (predoctoral fellowship to U.K.T.), the A. P. Sloan Foundation, the Research Corporation, Pfizer, Novartis, Merck, Amgen, Lilly, Roche, Abbott, AstraZeneka, GlaxoSmithKline, and Caltech for financial support.", revision_no = "15", abstract = "An efficient and mild acyl-alkylation of arynes is described. The method is used to synthesize medium-sized carbocycles by the ring-expansion of cyclic β-ketoesters.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/4942, title ="A ligand-free solid-supported system for Sonogashira couplings: applications in nucleoside chemistry", author = "Garg, Neil K. and Woodroofe, Carolyn C.", journal = "Chemical Communications", volume = "2005", number = "36", pages = "4551-4553", month = "January", year = "2005", doi = "10.1039/b505737j", issn = "1359-7345", url = "https://resolver.caltech.edu/CaltechAUTHORS:GARcc05", note = "© The Royal Society of Chemistry 2005 \n\nReceived (in Bloomington, IN, USA) 25th April 2005, Accepted 16th May 2005. First published on the web 12th August 2005 \n\nThe authors thank the NIH (R01 HG003594), the Rosen Fellowship (for C.J.L.) and the NDSEG (pre-doctoral fellowship to N.K.G.) for financial support. We also thank E. James Petersson for helpful discussions. \n\nExperimental details and 1H NMR spectra for all compounds (supplementary information)", revision_no = "17", abstract = "A mild heterogeneous, ligand-free protocol for Sonogashira and Heck couplings has been developed and used to access several biologically important deoxynucleoside derivatives in a facile manner.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/76757, title ="The Enantioselective Tsuji Allylation", author = "Behenna, Douglas C. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "126", number = "46", pages = "15044-15045", month = "November", year = "2004", doi = "10.1021/ja044812x", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170420-084322708", note = "© 2004 American Chemical Society. \n\nReceived 27 August 2004. Published online 28 October 2004. Published in print 1 November 2004. \n\nThe authors are grateful to the Fannie and John Hertz Foundation (predoctoral fellowship to D.C.B.), Caltech, the A. P. Sloan Foundation, and Research Corporation for financial support, and E. Kwei for experimental assistance.", revision_no = "15", abstract = "The first catalytic enantioselective examples of the Tsuji allylation using enol carbonates and enol silanes are described. The products possess a quaternary stereogenic center and are useful building blocks for synthetic chemistry.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74333, title ="The Enantioselective Tsuji Allylation", author = "Behenna, Douglas C. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "126", number = "46", pages = "15044-15045", month = "November", year = "2004", doi = "10.1021/ja044812x", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-141008792", note = "© 2004 American Chemical Society. \n\nReceived August 27, 2004. \n\nThe authors are grateful to the Fannie and John Hertz Foundation (predoctoral fellowship to D.C.B.), Caltech, the A. P. Sloan Foundation, and Research Corporation for financial support, and E. Kwei for experimental assistance.", revision_no = "14", abstract = "The first catalytic enantioselective examples of the Tsuji allylation using enol carbonates and enol silanes are described. The products possess a quaternary stereogenic center and are useful building blocks for synthetic chemistry.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74425, title ="Direct Oxidative Heck Cyclizations: Intramolecular Fujiwara-Moritani Arylations for the Synthesis of Functionalized Benzofurans and Dihydrobenzofurans", author = "Zhang, Haiming and Ferreira, Eric M.", journal = "Angewandte Chemie International Edition", volume = "43", number = "45", pages = "6144-6148", month = "November", year = "2004", doi = "10.1002/anie.200461294", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170221-114810808", note = "© 2004 Wiley. \n\nIssue online: 17 November 2004; version of record online: 17 November 2004; manuscript Received: 13 July 2004. \n\nThe authors wish to thank the NIH-NIGMS (R01 GM65961-01), the NSF (predoctoral fellowship to E.M.F.), Johnson and Johnson, Pfizer, Merck, Amgen, Research Corporation, Roche, GlaxoSmith-Kline, and Eli Lilly for generous funding.", revision_no = "13", abstract = "No extra functionalization step is required for palladium(II)-catalyzed oxidative carbocyclizations like that shown, which provide highly substituted benzofuran and dihydrobenzofuran derivatives by net dehydrogenation. The mechanism is similar to that of Heck cyclizations. Products containing quaternary carbon stereocenters can be obtained in diastereomerically pure form.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74344, title ="The Total Synthesis of (+)-Dragmacidin F", author = "Garg, Neil K. and Caspi, Daniel D.", journal = "Journal of the American Chemical Society", volume = "126", number = "31", pages = "9552-9553", month = "August", year = "2004", doi = "10.1021/ja046695b", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-153256032", note = "© 2004 American Chemical Society. \n\nReceived June 4, 2004; Publication Date (Web): July 20, 2004. \n\nWe are grateful to the NIH-NIGMS (R01 GM65961-01), DOD (NDSEG graduate fellowship to N.K.G.), and Eli Lilly (predoctoral fellowship to D.D.C.) for generous financial support. The Dervan lab is acknowledged for helpful discussions and the generous use of instrumentation. We also thank Drs. R. Riccio and A. Casapullo for an authentic sample of (−)-dragmacidin F.", revision_no = "13", abstract = "The first total synthesis of (+)-dragmacidin F has been accomplished, establishing the absolute configuration of this biologically important, antiviral marine alkaloid. The convergent route described features a palladium-mediated oxidative pyrrole carbocylization reaction to construct the [3.3.1] bicycle, as well as a highly selective Suzuki coupling to build the carbon skeleton of the natural product. A late-stage Neber rearrangement allows for the facile installation of the aminoimidazole moiety to provide (+)-dragmacidin F. ", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74343, title ="A Computational Model Relating Structure and Reactivity in Enantioselective Oxidations of Secondary Alcohols by (−)-Sparteine−Pd^(II) Complexes", author = "Nielsen, Robert J. and Keith, Jason M.", journal = "Journal of the American Chemical Society", volume = "126", number = "25", pages = "7967-7974", month = "June", year = "2004", doi = "10.1021/ja031911m", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-152829202", note = "© 2004 American Chemical Society. \n\nReceived 23 December 2003. Published online 4 June 2004. Published in print 1 June 2004. \n\nWe thank Eric Ferreira, Jeffrey Bagdanoff, Raissa Trend, Julius Su, and Jonas Oxgaard for helpful discussions. J.M.K. thanks the National Science Foundation for financial support. This research was partly funded by the NSF (CTS-01322002), ChevronTexaco, and the NIH-NIGMS (R01 GM65961-01), and the facilities used were funded by grants from ARO-DURIP, ONR- DURIP, IBM-SUR, and the Beckman Institute. All calculations were performed with Jaguar 4.0 and Jaguar 5.0.35", revision_no = "16", abstract = "The key interactions responsible for the unique reactivity of (−)-sparteine−PdX_2 complexes (X = chloride, acetate) in the enantioselective oxidation of secondary alcohols have been elucidated using quantum mechanics (B3LYP DFT with the PBF polarizable continuum solvent model). From examining many possible pathways, we find the mechanism involves:\u2009 (1) substitution of the alcohol in place of an X-group, (2) deprotonation of the bound alcohol by the deposed anion and free sparteine, (3) β-hydride elimination through a four-coordinate transition state in which the second anion is displaced but tightly associated, (4) replacement of the ketone product with the associated anion. The enantioselectivities observed under base-rich reaction conditions follow directly from calculated energies of diastereomeric β-hydride elimination transition states incorporating (R) and (S) substrates. This relationship reveals an important role of the anion, namely to communicate the steric interaction of the ligand on one side of the PdII square plane and the substrate on the other side. When no anion is included, no enantioselectivity is predicted. Locating these transition states in different solvents shows that higher dielectrics stabilize the charge separation between the anion and metal and draw the anion farther into solution. Thus, the solvent influences the barrier height (rate) and selectivity of the oxidation.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74359, title ="An Experimentally Derived Model for Stereoselectivity in the Aerobic Oxidative Kinetic Resolution of Secondary Alcohols by (Sparteine)PdCl_2", author = "Trend, Raissa M. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "126", number = "14", pages = "4482-4483", month = "April", year = "2004", doi = "10.1021/ja039551q", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170216-072248452", note = "© 2004 American Chemical Society. \n\nReceived 11 November 2003. Published online 18 March 2004. Published in print 1 April 2004. \n\nWe are grateful to Caltech and the A. P. Sloan Foundation for financial support. We are indebted to Dr. M. W. Day and Mr. L. M. Henling for X-ray crystallographic expertise as well as to Professors J. E. Bercaw, R. H. Grubbs, H. B. Gray, and J. C. Peters and their groups for assistance and helpful discussions.", revision_no = "16", abstract = "A model for asymmetric induction in palladium-catalyzed aerobic oxidative kinetic resolution is described. The model is based on coordination complexes and general reactivity trends of the parent (sp)PdCl2 catalyst. The first example of a nonracemic chiral palladium alkoxide complex is presented, and exhibits the subtle steric influences of the C1symmetric ligand sparteine.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74360, title ="Substituent Effects and Nearly Degenerate Transition States: Rational Design of Substrates for the Tandem Wolff−Cope Reaction", author = "Su, Julius T. and Sarpong, Richmond", journal = "Journal of the American Chemical Society", volume = "126", number = "1", pages = "24-25", month = "January", year = "2004", doi = "10.1021/ja037716p", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170216-074904738", note = "© 2004 American Chemical Society. \n\nReceived 1 August 2003. Published online 12 December 2003. Published in print 1 January 2004. \n\nWe thank NSF (WAG, predoctoral fellowship to J.T.S.), and Pfizer·UNCF (postdoctoral fellowship for R.S.) for financial support. We also thank J. Oxgaard and R. Nielsen for useful discussions.", revision_no = "13", abstract = "The substrate scope for a ketene-assisted Cope (tandem Wolff−Cope) reaction is elucidated from first-principles quantum mechanics. An alternate pathway (trans) leading to an undesired and unstable product lies perilously close (∼2.5 kcal/mol) to the primary (cis) reaction pathway; this near-degeneracy arises from preferential ketene stabilization of a radicaloid trans transition state over an aromatic cis transition state. Normally, substitution at “forbidden” sites causes the alternate pathway to be favored and the reaction to fail, but using simple conformational analysis principles we design substrates that defy this rule.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74337, title ="Palladium-Catalyzed Oxidative Kinetic Resolution with Ambient Air as the Stoichiometric Oxidation Gas", author = "Bagdanoff, Jeffrey T. and Stoltz, Brian M.", journal = "Angewandte Chemie International Edition", volume = "43", number = "3", pages = "353-357", month = "January", year = "2004", doi = "10.1002/anie.200352444", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-145714988", note = "© 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nIssue online: 29 December 2003; Version of record online: 29 December 2003; Manuscript Received: 22 July 2003. \n\nThe authors thank the NIH-NIGMS (R01 GM65961-01), the\nUniversity of California TRDRP (predoctoral fellowship to JTB), the Dreyfus Foundation, Merck Research Laboratories, Research Corporation, Abbott Laboratories, Eli Lilly, GlaxoSmithKline, Johnson and Johnson, Pfizer, and the A. P. Sloan Foundation for generous financial support.", revision_no = "10", abstract = "Air is enough to mediate the highly enantioselective oxidation of secondary alcohols at room temperature with palladium(II) and sparteine in nonflammable solvents. Examination of the role of solvents capable of hydrogen bonding and their ability to solvate halide anions led to a novel set of conditions for the highly enantioselective oxidative kinetic resolution of secondary alcohols.\n", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74361, title ="The Total Synthesis of (−)-Lemonomycin", author = "Ashley, Eric R. and Cruz, Ernest G.", journal = "Journal of the American Chemical Society", volume = "125", number = "49", pages = "15000-15001", month = "December", year = "2003", doi = "10.1021/ja039223q", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170216-075818295", note = "© 2003 American Chemical Society. \n\nReceived 24 October 2003. Published online 14 November 2003. Published in print 1 December 2003. \n\nThis work is dedicated to Professor E. J. Corey on the occasion of his 75th birthday. The authors are grateful to Caltech, the University of California TRDRP (predoctoral fellowship to E.R.A.), and the J. Irvine Foundation (predoctoral fellowship to E.G.C.) for financial support. We also thank T. Y. Lam for experimental assistance and Dr. H. He (Wyeth-Ayerst) for an authentic sample of (−)-1.", revision_no = "29", abstract = "The first total synthesis of the novel glycosylated tetrahydroisoquinoline antitumor antibiotic (−)-lemonomycin has been accomplished (15 steps from 9). The highly convergent synthesis relies on a key asymmetric dipolar cycloaddition to set the stereochemistry of the aglycone core, a Suzuki fragment coupling to connect the diazabicycle to the aryl subunit, and a stereoselective Pictet−Spengler reaction that incorporates the aminoglycoside subunit directly into the core structure without the need for late-stage glycosylation or protecting group manipulations. The novel aminoglycoside was prepared using a highly diastereoselective Felkin-controlled acetate aldol addition reaction to a threonine-derived ketone.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74335, title ="The Development of a Facile Tandem Wolff/Cope Rearrangement for the Synthesis of Fused Carbocyclic Skeletons", author = "Sarpong, Richmond and Su, Julius T.", journal = "Journal of the American Chemical Society", volume = "125", number = "45", pages = "13624-13625", month = "November", year = "2003", doi = "10.1021/ja037587c", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-143652773", note = "© 2003 American Chemical Society. \n\nReceived 29 July 2003. Published online 16 October 2003. Published in print 1 November 2003. \n\nWe are grateful to Research Corporation, Pfizer·UNCF (postdoctoral fellowship to R.S.), and the NSF (predoctoral fellowship to J.T.S.) for generous financial support. We also thank Neil K. Garg for assisting with advanced NMR experiments.", revision_no = "14", abstract = "A set of mild processes for the conversion of vinyl cyclopropyl diazo ketones to highly functionalized cycloheptadienones and vinyl cyclopentenones by use of a target-inspired tandem Wolff/Cope rearrangement sequence is described. A divergent reaction course of the vinyl cyclopropyl diazo ketone substrates under sono- or photochemical activation provides good to excellent yields (55−98%) of the product cycloheptadienones and vinyl cyclopentenones.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74363, title ="Catalytic C−H Bond Functionalization with Palladium(II): Aerobic Oxidative Annulations of Indoles", author = "Ferreira, Eric M. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "125", number = "32", pages = "9578-9579", month = "August", year = "2003", doi = "10.1021/ja035054y", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170216-082726177", note = "© 2003 American Chemical Society. \n\nReceived 7 March 2003. Published online 22 July 2003. Published in print 1 August 2003. \n\nWe thank the NIH-NIGMS (GM65961-01) and the NSF (predoctoral fellowship to E.M.F.) for generous financial support, and Professors András Kotschy and Greg Fu for stimulating discussions.", revision_no = "14", abstract = "A palladium-catalyzed aerobic oxidative annulation of indoles is described. We have demonstrated that a variety of factors influence these cyclizations, and in particular the electronic nature of the pyridine ligand is crucial. It is also remarkable that these oxidative cyclizations can proceed in good yield despite background oxidative decomposition pathways, testament to the facile nature with which molecular oxygen can serve as the direct oxidant for Pd(0). We have also shown that the mechanism most likely involves initial indole palladation (formal C−H bond activation) followed by migratory insertion and β-hydrogen elimination.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74429, title ="Palladium-Catalyzed Oxidative Wacker Cyclizations in Nonpolar Organic Solvents with Molecular Oxygen: A Stepping Stone to Asymmetric Aerobic Cyclizations", author = "Trend, Raissa M. and Ramtohul, Yeeman K.", journal = "Angewandte Chemie International Edition", volume = "42", number = "25", pages = "2892-2895", month = "June", year = "2003", doi = "10.1002/anie.200351196", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170221-131404095", note = "© 2003 Wiley. \n\nIssue online 24 June 2003; version of record online 24 June 2003; manuscript received 17 February 2003. \n\nThe authors wish to thank the NIH-NIGMS (R01 GM65961-01), the University of California TRDRP (postdoctoral fellowship to YKR), the NSF (predoctoral fellowship to EMF), the Dreyfus Foundation, Merck Research Laboratories, Research Corporation, and Abbott Laboratories for generous financial support. Dr. Richmond Sarpong and Mr. Julius Su are gratefully acknowledged for molecular modeling assistance.", revision_no = "13", abstract = "A variety of Pd-catalyzed oxidative nucleophile/alkene cyclizations proceeds in excellent yield under simple aerobic conditions in nonpolar media (Pd catalyst, pyridine, and O_2 in toluene). Nucleophiles for these cyclizations include phenols, carboxylic acids, amides, and primary alcohols. Additionally, enantioselective catalysis is feasible with a Pd-sparteine system (see picture). Enantioselectivities of up to 90\u2009% ee are observed for simple phenol/alkene cyclizations.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74340, title ="Gas-Phase Synthesis of Charged Copper and Silver Fischer Carbenes from Diazomalonates: Mechanistic and Conformational Considerations in Metal-Mediated Wolff Rearrangements", author = "Julian, Ryan R. and May, Jeremy A.", journal = "Journal of the American Chemical Society", volume = "125", number = "15", pages = "4478-4486", month = "April", year = "2003", doi = "10.1021/ja028337j", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-152031857", note = "© 2003 American Chemical Society. \n\nReceived 29 August 2002. Published online 19 March 2003. Published in print 1 April 2003. \n\nThe authors gratefully acknowledge funding provided by NSF (Grant CHE-9727566), the Beckman Institute Foundation, the California Institute of Technology, the Camille and Henry Dreyfus Foundation (New Faculty Award to B.M.S.), and Abbott Labs (graduate fellowship to J.A.M.).", revision_no = "11", abstract = "Copper(I) and silver(I) Fischer carbenes are synthesized in the gas phase. Various diazomalonate-based compounds with an attached metal ion are introduced into the gas phase by electrospray ionization and subjected to collisional activation. Loss of N2 generates a metastable Fischer carbene, which subsequently undergoes Wolff rearrangement and loss of CO. Further excitation leads to the loss of another CO molecule and the generation of a stable Fischer carbene. Isotopically labeled compounds are utilized to confirm the assignment of the products resulting from this process. DFT calculations are used to evaluate various mechanistic possibilities and to quantitatively assess the energetics of reactants and products. Silver(I) is shown to be more effective in facilitating Wolff rearrangement than copper(I), although both are more effective when compared to spectator charges such as sodium or a fixed quaternary nitrogen. Carbenes are not produced when copper(II), nickel(II), or a proton is used to form a quasi-molecular ion from the diazomalonate carbene precursor. Finally, trapping of the Fischer carbene by various functional groups attached through the open coordination site of the metal is investigated.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74472, title ="Palladium-Catalyzed Enantioselective Oxidation of Alcohols: A Dramatic Rate Acceleration by Cs_2CO_3/t-BuOH", author = "Bagdanoff, Jeffrey T. and Ferreira, Eric M.", journal = "Organic Letters", volume = "5", number = "6", pages = "835-837", month = "March", year = "2003", doi = "10.1021/ol027463p", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-145100100", note = "© 2003 American Chemical Society. \n\nReceived 13 December 2002. Published online 14 February 2003. Published in print 1 March 2003. \n\nWe wish to thank the NIH-NIGMS (R01 GM65961-01), the California Institute of Technology, the Camille and Henry Dreyfus Foundation (New Faculty Award to B.M.S.), the Merck Research Laboratories, Research Corporation, The University of California TRDRP (predoctoral fellowship to J.T.B.), the National Science Foundation (predoctoral fellowship to E.M.F.), GlaxoSmithKline, and Abbott Laboratories for generous financial support.", revision_no = "14", abstract = "The addition of Cs_2CO_3 and t-BuOH provides a dramatic rate acceleration in the palladium-catalyzed aerobic oxidative kinetic resolution of secondary alcohols while maintaining the selectivity of the process.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74515, title ="Molecular Mousetraps: Gas-Phase Studies of the Covalent Coupling of Noncovalent Complexes Initiated by Reactive Carbenes Formed by Controlled Activation of Diazo Precursors", author = "Julian, Ryan R. and May, Jeremy A.", journal = "Angewandte Chemie International Edition", volume = "42", number = "9", pages = "1012-1015", month = "March", year = "2003", doi = "10.1002/anie.200390258", issn = "1433-7851", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170223-161950902", note = "© 2003 John Wiley & Sons.\n\nReceived: October 23, 2002. \n\nThe authors gratefully acknowledge funding provided by NSF (Grant CHE-9727566), the Beckman Institute Foundation, the California Institute of Technology, the Camille and Henry Dreyfus Foundation (New Faculty Award to B.M.S.), and Abbott Labs (graduate fellowship to J.A.M.). Special thanks to the Peter Dervan group for aid in the use of their HPLC apparatus.", revision_no = "11", abstract = "The covalent linking of noncovalently bound host–guest complexes in the gas phase is achieved by the formation of a highly reactive carbene from the host molecule, which is generated by collision-activated dissociation. Possible mechanisms for the resulting intermolecular reactions are explored by theory and experiment.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74334, title ="The First Total Synthesis of Dragmacidin D", author = "Garg, Neil K. and Sarpong, Richmond", journal = "Journal of the American Chemical Society", volume = "124", number = "44", pages = "13179-13184", month = "November", year = "2002", doi = "10.1021/ja027822b", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-142231422", note = "© 2002 American Chemical Society. \n\nReceived 23 July 2002. Published online 5 October 2002. Published in print 1 November 2002. \n\nThe authors are grateful to the California Institute of Technology, the Camille and Henry Dreyfus Foundation (New Faculty Award to B.M.S.), Merck Research Laboratories, NIH-NIGMS (R01 GM65961-01), DOD (NDSEG graduate fellowship to N.K.G.), and Pfizer·UNCF (postdoctoral fellowship to R.S.) for generous financial support. The Dervan and MacMillan labs are acknowledged for helpful discussions and the generous use of instrumentation. Michael Marques, Wei Zhang, and Yen Nguyen are acknowledged for experimental assistance. We thank John Greaves (University of California, Irvine) for obtaining high-resolution mass spectra and Scott Ross of the Beckman Institute (Caltech) for assistance in obtaining NMR spectra. We gratefully acknowledge Dr. Amy E. Wright of the Harbor Branch Oceanographic Institute (North Fort Pierce, Florida) and Professor Robert J. Capon of the University of Melbourne (Parkville, Victoria, Australia) for kindly providing samples and spectra of natural dragmacidin D.", revision_no = "14", abstract = "The first total synthesis of the biologically significant bis-indole alkaloid dragmacidin D (5) has been achieved. Thermal and electronic modulation provides the key for a series of palladium-catalyzed Suzuki cross-coupling reactions that furnished the core structure of the complex guanidine- and aminoimidazole-containing dragmacidins. Following this crucial sequence, a succession of meticulously controlled final events was developed leading to the completion of the natural product.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74338, title ="Non-Carbonyl-Stabilized Metallocarbenoids in Synthesis: The Development of a Tandem Rhodium-Catalyzed Bamford−Stevens/Thermal Aliphatic Claisen Rearrangement Sequence", author = "May, Jeremy A. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "124", number = "42", pages = "12426-12427", month = "October", year = "2002", doi = "10.1021/ja028020j", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-150235551", note = "© 2002 American Chemical Society. \n\nReceived 5 August 2002. Published online 1 October 2002. Published in print 1 October 2002. \n\nThe authors wish to thank the NSF (CHE-0135056), the Dreyfus Foundation, Merck Research Laboratories, and Abbott Laboratories for financial support.", revision_no = "13", abstract = "A tandem rhodium-catalyzed Bamford−Stevens/Claisen rearrangement is presented. The tandem reaction uses Eschenmoser hydrazones for the in situ generation of non-carbonyl-stabilized diazo alkanes, which are presumably intercepted by Rh(II) catalysts to induce a 1,2-hydride migration. This sequence provides high levels of stereocontrol for the generation of simple acyclic (Z)-enol ethers. These enol ethers undergo either thermal or Lewis acid accelerated Claisen rearrangements to provide products of high diastereopurity. Also presented are cascade reactions, wherein a third chemical step occurs after the initial tandem sequence (i.e., Bamford−Stevens/Claisen/ene and Bamford−Stevens/Claisen/Cope).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74332, title ="Progress toward the Synthesis of Garsubellin A and Related Phloroglucins: The Direct Diastereoselective Synthesis of the Bicyclo[3.3.1]nonane Core", author = "Spessard, Sarah J. and Stoltz, Brian M.", journal = "Organic Letters", volume = "4", number = "11", pages = "1943-1946", month = "May", year = "2002", doi = "10.1021/ol025968+", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-135249615", note = "© 2002 American Chemical Society. \n\nReceived April 3, 2002. Publication Date (Web): May 4, 2002. \n\nThe authors are grateful to the California Institute of Technology, the Camille and Henry Dreyfus Foundation (New Faculty Award to B.M.S.), Merck Research Laboratories, and Pharmacia (graduate fellowship to S.J.S.) for generous financial support. The Grubbs, MacMillan, and Hsieh-Wilson labs are acknowledged for helpful discussions and the use of chemicals and instrumentation. We thank Larry Henling and Michael Day for solving the X-ray crystal structure and John Greaves (UCI) for obtaining high-resolution mass spectra. The authors would also like to acknowledge Professors Gary Spessard and Gretchen Hofmeister for helpful discussions and advice.", revision_no = "13", abstract = "A highly diastereoselective single-step cyclization reaction provides access to the bicyclo[3.3.1]nonane core of the polyprenylated phloroglucin natural product garsubellin A. Further elaboration to a more functionalized analogue involves a sequential Claisen rearrangement/Grubbs olefin cross-metathesis strategy. Additionally, this strategy was extended to the preparation of the bis-quaternary carbon array found at the bridgehead positions of the phloroglucin natural products.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74330, title ="The Palladium-Catalyzed Oxidative Kinetic Resolution of Secondary Alcohols with Molecular Oxygen", author = "Ferreira, Eric M. and Stoltz, Brian M.", journal = "Journal of the American Chemical Society", volume = "123", number = "31", pages = "7725-7726", month = "August", year = "2001", doi = "10.1021/ja015791z", issn = "0002-7863", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-134639074", note = "© 2001 American Chemical Society. \n\nReceived March 9, 2001. Revised Manuscript Received June 19, 2001. \n\nWe are grateful to the California Institute of Technology, the Camille and Henry Dreyfus Foundation, and the Merck Research Laboratories for generous financial support. B.M.S. thanks the Camille and Henry Dreyfus Foundation for a New Faculty Award. We thank the MacMillan group for generously sharing their HPLC and GC equipment. We acknowledge Professors John E. Bercaw, Robert H. Grubbs, and David W. C. MacMillan and their groups for chemicals and helpful discussions.", revision_no = "13", abstract = "The oxidation of secondary alcohols is one of the most common and well-studied reactions in chemistry. Although excellent catalytic enantioselective methods exist for a variety of oxidation processes, such as epoxidation, dihydroxylation, and aziridination, it is surprising that there are relatively few catalytic enantioselective examples of the ubiquitous alcohol oxidation. In connection with a general program dealing with the discovery of new catalytic oxidation systems, we present herein the development of a catalytic oxidative kinetic resolution of secondary alcohols that uses molecular oxygen as the terminal oxidant (see Scheme 1).", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74329, title ="Synthesis of C(3) Benzofuran-Derived Bisaryl Quaternary Centers: Approaches to Diazonamide A", author = "Fuerst, Douglas E. and Stoltz, Brian M.", journal = "Organic Letters", volume = "2", number = "22", pages = "3521-3523", month = "November", year = "2000", doi = "10.1021/ol006578v", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170215-134104826", note = "© 2000 American Chemical Society. \n\nReceived September 11, 2000. Publication Date (Web): October 4, 2000. \n\nWe are pleased to acknowledge the support of this investigation by Bristol-Myers Squibb, Yamanouchi, Pfizer, and Merck. J.L.W. is a fellow of the Alfred P. Sloan Foundation.", revision_no = "13", abstract = "Two complementary strategies for the synthesis of the diazonamide A bisaryl quaternary center are described. The first strategy relies upon an extremely facile tandem cyclopropanation/ring-opening sequence, which has proven amenable to chiral catalysis to provide enantioenriched material. The second strategy relies upon a more concise alkylation route ideal for material advancement.", } @article {CaltechAUTHORS_https://authors.library.caltech.edu/id/eprint/74464, title ="Mechanistic Insights into the Factors Determining Exo−EndoSelectivity in the Lewis Acid-Catalyzed Diels−Alder Reaction of 1,3-Dienes with 2-Cycloalkenones", author = "Ge, Min and Stoltz, Brian M.", journal = "Organic Letters", volume = "2", number = "13", pages = "1927-1929", month = "June", year = "2000", doi = "10.1021/ol0060026", issn = "1523-7060", url = "https://resolver.caltech.edu/CaltechAUTHORS:20170222-101505337", note = "© 2000 American Chemical Society. \n\nReceived 1 May 2000. Published online 27 May 2000. Published in print 1 June 2000. \n\nThis research was assisted financially by a grant from the National Institutes of Health.", revision_no = "11", abstract = "We adduce evidence that the asynchronous, Lewis acid-catalyzed Diels−Alder reaction of 2-cycloalkenones with nonsimple α,β-enones can proceed via transition states in which the 1,3-diene subunit is skewed, i.e., nonplanar, with profound effects on the ratio of exo and endo addition products.", }