Nickel-Catalyzed Asymmetric Homobenzylic Hydroamidation of Aryl Alkenes to Access Chiral β-Arylamides

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Herein, we introduce a Ni-catalyzed asymmetric homobenzylic hydroamidation reaction that efficiently addresses the dual challenges of achieving regio- and enantioselectivity in synthesis β-(hetero)arylethylamides. By employing transposed NiH catalysis approach, this method facilitates formation key chiral nickel-amido intermediates, enabling insertion into alkenes to produce desired β-arylamide products with excellent enantioselectivity. The exhibits high functional group tolerance utilizes readily available starting materials vinylarenes react dioxazolone as robust amidating source. Notably, approach was successfully applied pharmaceutical compounds natural products, such Clobenzorex, Direx, Selegiline, Sacubitril, Cipargamin.

Язык: Английский

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Control of Axial Chirality through NiH-Catalyzed Atroposelective Hydrofunctionalization of Alkynes

ACS Catalysis, Год журнала: 2023, Номер 13(6), С. 3841 - 3846

Опубликована: Март 3, 2023

Catalytic asymmetric hydrofunctionalization of alkenes is a well-established method with which to construct complex C(sp3)-enriched molecules central chirality. In contrast, the use catalytic abundant alkyne substrates produce valuable multisubstituted axial chirality remains largely unexplored. Here, we report general procedure this type catalyzed by Ni(II) salts and employing structurally simple chiral PyrOx ligand. A wide variety diverse atropisomeric styrenes have been obtained from hydroarylation alkynes high efficiency, complete Z-selectivity, excellent enantioselectivity.

Язык: Английский

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Development of a Nickel-Catalyzed N–N Coupling for the Synthesis of Hydrazides

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(28), С. 15071 - 15077

Опубликована: Июль 6, 2023

A nickel-catalyzed N-N cross-coupling for the synthesis of hydrazides is reported. O-Benzoylated hydroxamates were efficiently coupled with a broad range aryl and aliphatic amines via nickel catalysis to form in an up 81% yield. Experimental evidence implicates intermediacy electrophilic Ni-stabilized acyl nitrenoids formation Ni(I) catalyst silane-mediated reduction. This report constitutes first example intermolecular coupling compatible secondary amines.

Язык: Английский

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Stereodivergent, Kinetically Controlled Isomerization of Terminal Alkenes via Nickel Catalysis

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(21)

Опубликована: Март 18, 2024

Abstract Because internal alkenes are more challenging synthetic targets than terminal alkenes, metal‐catalyzed olefin mono‐transposition (i.e., positional isomerization) approaches have emerged to afford valuable E ‐ or Z‐ from their complementary alkene feedstocks. However, the applicability of these methods has been hampered by lack generality, commercial availability precatalysts, and scalability. Here, we report a nickel‐catalyzed platform for stereodivergent / Z ‐selective synthesis at room temperature. Commercial reagents enable this one‐carbon transposition ‐internal via Ni−H‐mediated insertion/elimination mechanism. Though mechanistic regime is same in both systems, underlying pathways that lead each active catalysts distinct, with catalyst forming comproportionation an oxidative addition complex followed substrate protonation metal trialkylphosphonium salt additive. In case, ligand sterics denticity control stereochemistry prevent over‐isomerization.

Язык: Английский

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Nickel-catalyzed switchable arylative/endo-cyclization of 1,6-enynes

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 4, 2024

Abstract Carbo- and heterocycles are frequently used as crucial scaffolds in natural products, fine chemicals, biologically pharmaceutically active compounds. Transition-metal-catalyzed cyclization of 1,6-enynes has emerged a powerful strategy for constructing functionalized carbo- heterocycles. Despite significant progress, the regioselectivity alkyne functionalization is entirely substrate-dependent. And only exo -cyclization/cross-coupling products can be obtained, while endo -selective cyclization/cross-coupling remains elusive still poses formidable challenge. In this study, we disclose nickel-catalyzed switchable arylation/cyclization which nature ligand dictates arylation, electrophilic trapping reagents determine selectivity mode. Specifically, using commercially available 1,10-phenanthroline facilitates trans -arylation/cyclization to obtain seven-membered ring 2-naphthyl-substituted bisbox promotes cis access six-membered products. Diastereoselective cyclizations have also been developed synthesis enantioenriched piperidines azepanes, core structural elements pharmaceuticals possessing important biological activities. Furthermore, experimental density functional theory studies reveal that arylation process controlled by steric hindrance ligand; reaction mechanism involves -cyclization followed Dowd-Beckwith-type expansion form

Язык: Английский

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Enantioselective synthesis of α-aminoboronates by NiH-catalysed asymmetric hydroamidation of alkenyl boronates

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Сен. 26, 2022

Abstract Chiral α-aminoboronic acids and their derivatives are generally useful as bioactive compounds some have been approved therapeutic agents. Here we report a NiH-catalysed asymmetric hydroamidation process that with simple amino alcohol ligand can easily produce wide range of highly enantioenriched α-aminoboronates from alkenyl boronates dioxazolones under mild conditions. The reaction is proposed to proceed by an enantioselective hydrometallation followed inner-sphere nitrenoid transfer C–N bond forming sequence. synthetic utility this transformation was demonstrated the efficient synthesis current pharmaceutical agent, Vaborbactam.

Язык: Английский

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Intramolecular hydroamidation of alkenes enabling asymmetric synthesis of β-lactams via transposed NiH catalysis

Nature Catalysis, Год журнала: 2023, Номер 6(9), С. 784 - 795

Опубликована: Авг. 24, 2023

Язык: Английский

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Regio- and Enantioselective Nickel-Catalyzed Ipso- and Remote Hydroamination Utilizing Organic Azides as Amino Sources for the Synthesis of Primary Amines

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Окт. 23, 2024

Primary amines serve as key synthetic precursors to most other

Язык: Английский

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Photoexcited Direct Amination/Amidation of Inert Csp³–H Bonds via Tungsten–Nickel Catalytic Relay

ACS Catalysis, Год журнала: 2022, Номер 12(18), С. 11071 - 11077

Опубликована: Авг. 26, 2022

Light alkanes are the most abundant resources in nature. It is of great significance to develop convenient methods realize conversion high value-added products. However, examples aliphatic amines derived from unactivated remain rare. This work describes a rapid construction C(sp3)–N bonds light with amine/amide electrophile reagents via high-valent tungsten and nickel catalysis efficiency. The photoexcited metal relay provides powerful tool for activation inert sp3-hybridized C–H stabilization C–Ni(III)–N intermediates.

Язык: Английский

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NiH-catalyzed C–N bond formation: insights and advancements in hydroamination of unsaturated hydrocarbons

Chemical Science, Год журнала: 2023, Номер 15(2), С. 442 - 457

Опубликована: Дек. 6, 2023

The formation of C-N bonds is a fundamental aspect organic synthesis, and hydroamination has emerged as pivotal strategy for the synthesis essential amine derivatives. In recent years, there been surge interest in metal hydride-catalyzed reactions common alkenes alkynes. This method avoids need stoichiometric organometallic reagents overcomes problems associated with specific compounds that may impact functional group compatibility. Notably, developments have brought to forefront olefinic hydroamidation facilitated by nickel hydride (NiH) catalysis. inclusion suitable chiral ligands paved way realization asymmetric realm olefins. review aims provide an in-depth exploration latest achievements bond through intermolecular catalyzed hydrides. Leveraging this innovative approach, diverse range alkene alkyne substrates can be efficiently transformed into value-added enriched bonds. intricacies are succinctly elucidated, offering concise overview underlying reaction mechanisms. It our aspiration comprehensive will stimulate further progress NiH-catalytic techniques, fine-tune systems, drive innovation catalyst design, foster deeper understanding

Язык: Английский

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