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

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.