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

01 June 2020, Version 3
This content is a preprint and has not undergone peer review at the time of posting.

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.

Keywords

nitrene
silver
amination
asymmetric
propargylamine

Supplementary materials

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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
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