Computational Investigation on Copper(I)-Catalyzed Enantioselective Radical Borylation of Benzyl Halides

Abstract

α-Chiral alkyl boron compounds have multifaceted applications in organic synthesis and pharmaceuticals. To date, various catalytic and non-catalytic methods for the enantioselective synthesis have been developed. A copper(I)-catalyzed enantioselective borylation of multiple bonds, such as alkenes, is one of the reliable methods for preparation of the α-chiral alkyl boronates. In contrast, enantioconvergent borylations of racemic starting materials are highly challenging and unestablished. Recently, my co-workers in the Ito group developed the first copper(I)-catalyzed enantioconvergent boryl substitution of racemic benzyl chlorides. In this study, I performed density functional theory (DFT) calculations as the computational mechanistic study and analyzed the enantiodetermining transition states (TSs). Interaction analyses based on the non-covalent interaction (NCI) plot revealed that the combination of an attractive C–H/π interaction in the favored TS and steric repulsion in the disfavored TS contributes to the high enantioselectivity.