[
{
"id": "authors:etbwk-9kh91",
"collection": "authors",
"collection_id": "etbwk-9kh91",
"cite_using_url": "https://authors.library.caltech.edu/records/etbwk-9kh91",
"type": "article",
"title": "Photoinduced copper-catalysed deracemization of alkyl halides",
"author": [
{
"family_name": "Zhong",
"given_name": "Feng",
"clpid": "Zhong-Feng"
},
{
"family_name": "Li",
"given_name": "Renhe",
"orcid": "0000-0001-5269-4735",
"clpid": "Li-Renhe"
},
{
"family_name": "Mai",
"given_name": "Binh Khanh",
"orcid": "0000-0001-8487-1417"
},
{
"family_name": "Liu",
"given_name": "Peng",
"orcid": "0000-0002-8188-632X"
},
{
"family_name": "Fu",
"given_name": "Gregory C.",
"orcid": "0000-0002-0927-680X",
"clpid": "Fu-G-C"
}
],
"abstract": "Deracemization is an emerging strategy for generating enantioenriched compounds wherein the two enantiomers of a readily available racemic starting material are transformed into a single enantiomer, typically through the action of a light-induced catalyst. Excellent proof of principle for this potentially powerful approach to asymmetric catalysis has been described; nevertheless, substantial challenges have not yet been addressed, including the exploitation of carbon–heteroatom (rather than only carbon–hydrogen and carbon–carbon) bond cleavage to achieve deracemization, as well as the development of processes that provide broad classes of useful enantioenriched compounds and tetrasubstituted stereocentres. Here we describe a straightforward method that addresses these challenges, using a chiral copper catalyst, generated in situ from commercially available components, to achieve the photoinduced deracemization of tertiary (and secondary) alkyl halides through carbon–halogen bond cleavage. Mechanistic studies (including the independent synthesis of postulated intermediates, photophysical, spectroscopic and reactivity studies, and density functional theory calculations) provide support for the key steps and intermediates in our proposed catalytic cycle, as well as insight into the origin of enantioselectivity.
",
"doi": "10.1038/s41586-025-08784-8",
"pmcid": "PMC11970559",
"issn": "0028-0836",
"publisher": "Nature Publishing Group",
"publication": "Nature",
"publication_date": "2025-04-03",
"series_number": "8057",
"volume": "640",
"issue": "8057",
"pages": "107-113"
},
{
"id": "authors:gntt6-7jt81",
"collection": "authors",
"collection_id": "gntt6-7jt81",
"cite_using_url": "https://authors.library.caltech.edu/records/gntt6-7jt81",
"type": "article",
"title": "Photoinduced, Copper-Catalyzed Enantioconvergent Synthesis of \u03b2-Aminoalcohol Derivatives",
"author": [
{
"family_name": "Mondal",
"given_name": "Arup",
"orcid": "0000-0003-2643-1004",
"clpid": "Mondal-Arup"
},
{
"family_name": "Fu",
"given_name": "Gregory C.",
"orcid": "0000-0002-0927-680X",
"clpid": "Fu-G-C"
}
],
"abstract": "\n
In view of the frequent occurrence of carbon–nitrogen bonds in organic compounds, the development of powerful new methods for the construction of such bonds is expected to greatly impact many of the fields that utilize organic molecules. While the substitution of an alkyl electrophile by a nitrogen nucleophile is a seemingly straightforward approach to generating a carbon–nitrogen bond, in practice classical substitution pathways have very substantial limitations in the case of unactivated secondary and tertiary alkyl electrophiles. Recent reports that transition metals can catalyze certain substitution reactions of such electrophiles are therefore of considerable significance; however, virtually no methods have been developed wherein absolute stereochemistry is controlled together with carbon–nitrogen bond formation. Herein, we address this dual challenge of reactivity and enantioselectivity, describing a photoinduced, copper-catalyzed enantioconvergent synthesis of β-aminoalcohol derivatives via the coupling of anilines with racemic, unactivated β-haloethers. We apply this method to a catalytic asymmetric synthesis of metolachlor, and we report an array of mechanistic studies that are consistent with the reaction pathway that we propose.
\n
In view of the high propensity of tertiary alkyl amines to be bioactive, the development of new methods for their synthesis is an important challenge. Transition-metal catalysis has the potential to greatly expand the scope of nucleophilic substitution reactions of alkyl electrophiles; unfortunately, in the case of alkyl amines as nucleophiles, only one success has been described so far: the selective mono-alkylation of primary amines to form secondary amines. Here, using photoinduced copper catalysis, we report the synthesis of tertiary alkyl amines from secondary amines and unactivated alkyl electrophiles, two readily available coupling partners. Utilizing an array of tools, we have analysed the mechanism of this process; specifically, we have structurally characterized the three principal copper-based intermediates that are detected during catalysis and provided support for the key steps of the proposed catalytic cycle, including the coupling of a copper(II)–amine intermediate with an alkyl radical to form a C–N bond.
",
"doi": "10.1038/s41557-024-01692-w",
"issn": "1755-4330",
"publisher": "Nature Publishing Group",
"publication": "Nature Chemistry",
"publication_date": "2025-02",
"series_number": "2",
"volume": "17",
"issue": "2",
"pages": "271-278"
},
{
"id": "authors:y9zc0-fgm21",
"collection": "authors",
"collection_id": "y9zc0-fgm21",
"cite_using_url": "https://authors.library.caltech.edu/records/y9zc0-fgm21",
"type": "article",
"title": "Nickel-Catalyzed Enantioconvergent and Diastereoselective Allenylation of Alkyl Electrophiles: Simultaneous Control of Central and Axial Chirality",
"author": [
{
"family_name": "Hossain",
"given_name": "Asik",
"orcid": "0000-0001-8731-7083"
},
{
"family_name": "Anderson",
"given_name": "Robert L."
},
{
"family_name": "Zhang",
"given_name": "Claudia S."
},
{
"family_name": "Chen",
"given_name": "Peng-Jui",
"orcid": "0000-0002-3594-0081"
},
{
"family_name": "Fu",
"given_name": "Gregory C.",
"orcid": "0000-0002-0927-680X",
"clpid": "Fu-G-C"
}
],
"abstract": "\n
In recent years, remarkable progress has been described in the development of methods that simultaneously control vicinal stereochemistry, wherein both stereochemical elements are central chirality; in contrast, methods that control central and axial chirality are comparatively rare. Herein we report that a chiral nickel catalyst achieves the enantioconvergent and diastereoselective coupling of racemic secondary alkyl electrophiles with prochiral 1,3-enynes (in the presence of a hydrosilane) to generate chiral tetrasubstituted allenes that bear an adjacent stereogenic center. A carbon–carbon and a carbon–hydrogen bond are formed in this process, which provides good stereoselectivity and is compatible with an array of functional groups.
\n
Due to the significance of organofluorine compounds in disciplines ranging from medicine to agriculture to materials science, the invention of new methods for the creation of carbon\u2013fluorine bonds is an important objective. Among the underdeveloped dimensions in this area are the fluorination of hindered alkyl halides (particularly chlorides) and the discovery of catalysts for such fluorination processes. Herein, we report a mild method for the fluorination of unactivated tertiary alkyl chlorides (and bromides), catalyzed by inexpensive PPh\u2083. This straightforward process is compatible with a range of hindered electrophiles and a variety of functional groups.
",
"doi": "10.1021/jacs.3c11042",
"pmcid": "PMC10942731",
"issn": "0002-7863",
"publisher": "American Chemical Society",
"publication": "Journal of the American Chemical Society",
"publication_date": "2023-11-22",
"series_number": "46",
"volume": "145",
"issue": "46",
"pages": "25093-25097"
},
{
"id": "authors:g677n-tbn19",
"collection": "authors",
"collection_id": "g677n-tbn19",
"cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230725-746869000.33",
"type": "article",
"title": "Iron\u2010Catalyzed Reductive Cross\u2010Coupling of Alkyl Electrophiles with Olefins",
"author": [
{
"family_name": "Tong",
"given_name": "Xiaoyu",
"orcid": "0000-0002-1343-6335",
"clpid": "Tong-Xiaoyu"
},
{
"family_name": "Yang",
"given_name": "Ze\u2010Peng",
"clpid": "Yang-Ze\u2010Peng"
},
{
"family_name": "Del Angel Aguilar",
"given_name": "Carlos E.",
"clpid": "Del-Angel-Aguilar-Carlos-E"
},
{
"family_name": "Fu",
"given_name": "Gregory C.",
"orcid": "0000-0002-0927-680X",
"clpid": "Fu-G-C"
}
],
"abstract": "In terms of its abundance and its minimal toxicity, iron has advantages relative to other transition metals. Although alkyl\u2013alkyl bond construction is central to organic synthesis, examples of iron-catalyzed alkyl\u2013alkyl couplings of alkyl electrophiles are relatively sparse. Herein we report an iron catalyst that achieves cross-coupling reactions of alkyl electrophiles wherein olefins, in the presence of a hydrosilane, are used in place of alkylmetal reagents. Carbon\u2013carbon bond formation proceeds at room temperature, and the method employs commercially available components (Fe(OAc)\u2082, Xantphos, and Mg(OEt)\u2082); interestingly, this set of reagents can be applied directly to a distinct hydrofunctionalization of olefins, hydroboration. Mechanistic studies are consistent with the generation of an alkyl radical from the alkyl electrophile, as well as with reversibility for elementary steps that precede carbon\u2013carbon bond formation (olefin binding to iron and \u03b2-migratory insertion).",
"doi": "10.1002/anie.202306663",
"pmcid": "PMC10528270",
"issn": "1433-7851",
"publisher": "Wiley",
"publication": "Angewandte Chemie International Edition",
"publication_date": "2023-08-16",
"pages": "Art. No. e202306663"
},
{
"id": "authors:36510-q5p96",
"collection": "authors",
"collection_id": "36510-q5p96",
"cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230615-812791000.10",
"type": "article",
"title": "Copper-catalysed enantioconvergent alkylation of oxygen nucleophiles",
"author": [
{
"family_name": "Chen",
"given_name": "Caiyou",
"orcid": "0000-0001-7536-7139",
"clpid": "Chen-Caiyou"
},
{
"family_name": "Fu",
"given_name": "Gregory C.",
"orcid": "0000-0002-0927-680X",
"clpid": "Fu-G-C"
}
],
"abstract": "\n
\n
Because carbon–oxygen bonds are commonplace in organic molecules, including chiral bioactive compounds, the development of new methods for their construction with simultaneous control of stereoselectivity is an important objective in synthesis. The Williamson ether synthesis, first reported in 1850 (1), is the most widely used approach to the alkylation of an oxygen nucleophile, but it has significant limitations (scope and stereochemistry) due to its reaction mechanism (SN2 pathway). Transition-metal catalysis of the coupling of an oxygen nucleophile with an alkyl electrophile has the potential to address these limitations, but progress to date has been very limited (2–7), especially with regard to controlling enantioselectivity. Herein we establish that a readily available copper catalyst can achieve an array of enantioconvergent substitution reactions of α-haloamides, a useful family of electrophiles, by oxygen nucleophiles; the reaction proceeds under mild conditions in the presence of a wide variety of functional groups. The catalyst is uniquely effective in being able to achieve enantioconvergent alkylations not only of oxygen nucleophiles, but also of nitrogen nucleophiles, furnishing support for the potential of transition-metal catalysts to provide a solution to the pivotal challenge of achieving enantioselective alkylations of heteroatom nucleophiles.
\n
\n