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

preprint
revised on 29.05.2020 and posted on 01.06.2020 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.

Funding

NSF 1664374

History

Email Address of Submitting Author

schomakerj@chem.wisc.edu

Institution

University of Wisconsin-Madison

Country

USA

ORCID For Submitting Author

0000-0003-1329-950X

Declaration of Conflict of Interest

There is no conflict of interest.

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