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

revised on 29.05.2020, 16:57 and posted on 01.06.2020, 06:13 by minsoo ju, Emily Zerull, Jessica Roberts, Minxue Huang, Jennifer Schomaker
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.


NSF 1664374


Email Address of Submitting Author


University of Wisconsin-Madison



ORCID For Submitting Author


Declaration of Conflict of Interest

There is no conflict of interest.