Silver-Catalyzed Enantioselective Propargylic C–H Bond Amination through Rational Ligand Design
Minsoo Ju, Emily E. Zerull, Jessica M. Roberts, Minxue Huang, Ilia A. Guzei, Jennifer M. Schomaker
Abstract
Asymmetric C–H amination via nitrene transfer is a powerful tool to prepare enantioenriched amine precursors from abundant C–H bonds. Herein, we report a regio- and enantioselective synthesis of γ-alkynyl γ-aminoalcohols via a silver-catalyzed propargylic C–H amination. The protocol was enabled by a new bis(oxazoline) (BOX) ligand designed via a rapid structure–activity relationship (SAR) analysis. The method utilizes accessible carbamate esters bearing γ-propargylic C–H bonds and furnishes versatile products in good yields and excellent enantioselectivity (90–99% ee). The putative Ag–nitrene is proposed to undergo enantiodetermining hydrogen-atom transfer (HAT) during the C–H amination event. Density functional theory calculations shed insight into the origin of enantioselectivity in the HAT step.