Organic Chemistry

Silver-Catalyzed Enantioselective Propargylic C–H Bond Amination Through Rational Ligand Design

Authors

Abstract

Asymmetric C–H amination via nitrene transfer (NT) is a powerful tool for the preparation of enantioenriched amine building blocks from abundant C–H bonds. Herein, we report a highly regio- and enantioselective synthesis of -alkynyl -amino alcohol motifs via a silver-catalyzed propargylic C–H amination. The protocol was enabled by development of a new bis(oxazoline) (BOX) ligand through a rapid structure-activity relationship (SAR) analysis. The method utilizes readily accessible carbamate ester substrates bearing -propargylic C–H bonds and furnishes versatile products in good yields and with excellent enantioselectivity (90–99% ee). A putative Ag–nitrene intermediate is proposed to undergo an enantiodetermining hydrogen-atom transfer (HAT) during the C–H amination event. Density functional theory (DFT) calculations were performed to investigate the origin of enantioselectivity in the HAT step.

Content

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Supplementary material

Thumbnail image of Silver-Catalyzed Enantioselective Propargylic C–H Bond Amination Through Rational Ligand Design SI.pdf
Silver-Catalyzed Enantioselective Propargylic C–H Bond Amination Through Rational Ligand Design SI
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RE Final version
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Final JACS asymmetric NT in template May 26 2020 resaved