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Silver-Catalyzed Enantioselective Propargylic C–H Bond Amination Through Rational Ligand Design
preprintrevised 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.
Email Address of Submitting Authorschomakerj@chem.wisc.edu
InstitutionUniversity of Wisconsin-Madison
ORCID For Submitting Author0000-0003-1329-950X
Declaration of Conflict of InterestThere is no conflict of interest.
Read the published paper
in Journal of the American Chemical Society