Cu-catalyzed enantioconvergent deborylative alkynylation
Joshua F. Head, Tanner J. Schubert, Biyu Zhao, Yuyang Dong
Abstract
Alkylboronic pinacol esters represent a highly attractive class of reagents due to their modular synthesis and unique reactivity conferred by the vacant boron p-orbital. However, their direct application in asymmetric C-C cross-coupling reactions remains underexplored. Herein, we report a Cu-catalyzed deborylative strategy to access α-chiral alkynes that delivers good enantioselectivity and accommodates a broad range of functional groups and heterocycles. The reaction is proposed to proceed through a radical-relay pathway: an aminyl radical-mediated C-B bond cleavage followed by Cu-catalyzed asymmetric alkynylation. The reaction mechanism was probed using a combination of radical clock ring-opening study, radical trapping experiments, and enantioconvergence test with enantioenriched starting materials. Density functional theory (DFT) calculations demonstrate the feasibility of a Cu-mediated inner-sphere C-C bond-forming pathway and attribute the observed enantioselectivity to attractive ligand-substrate halogen-π interactions.