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Silver-Catalyzed Enantioselective Propargylic C-H Bond Amination through Rational Ligand Design.

ABSTRACT: Asymmetric C-H amination via nitrene transfer is a powerful tool to prepare enantioenriched amine precursors from abundant C-H bonds. Herein, we report a regio- and enantioselective synthesis of γ-alkynyl γ-aminoalcohols via a silver-catalyzed propargylic C-H amination. The protocol was enabled by a new bis(oxazoline) (BOX) ligand designed via a rapid structure-activity relationship (SAR) analysis. The method utilizes accessible carbamate esters bearing γ-propargylic C-H bonds and furnishes versatile products in good yields and excellent enantioselectivity (90-99% ee). The putative Ag-nitrene is proposed to undergo enantiodetermining hydrogen-atom transfer (HAT) during the C-H amination event. Density functional theory calculations shed insight into the origin of enantioselectivity in the HAT step.

SUBMITTER: Ju M

PROVIDER: S-EPMC8294079 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Silver-Catalyzed Enantioselective Propargylic C-H Bond Amination through Rational Ligand Design.

Ju Minsoo M Zerull Emily E EE Roberts Jessica M JM Huang Minxue M Guzei Ilia A IA Schomaker Jennifer M JM

Journal of the American Chemical Society 20200716 30

Asymmetric C-H amination via nitrene transfer is a powerful tool to prepare enantioenriched amine precursors from abundant C-H bonds. Herein, we report a regio- and enantioselective synthesis of γ-alkynyl γ-aminoalcohols via a silver-catalyzed propargylic C-H amination. The protocol was enabled by a new bis(oxazoline) (BOX) ligand designed via a rapid structure-activity relationship (SAR) analysis. The method utilizes accessible carbamate esters bearing γ-propargylic C-H bonds and furnishes vers ...[more]

PMID: 32659081

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