Synthesis of Chiral Benzylamines via Nickel-Catalyzed Enantioselective C–H Alkynylation

Abstract

The enantioselective C–H functionalization of benzylamines using earth-abundant metal catalysts remains a formidable challenge due to conformational flexibility and long-range chiral induction. Herein, we describe a Ni(II)-catalyzed enantioselective C–H alkynylation of benzylamines using a removable picolinamide directing group. A sterically bulky (S)-3,3′-di(naphthalen-1-yl)-BINOL ligand creates a well-defined chiral pocket around the nickel center, enabling precise stereocontrol (up to >99% ee). Notably, in contrast to conventional C–H alkynylation reactions that typically require sterically bulky alkynyl bromides, our system tolerates a broad range of less sterically hindered alkynyl partners, including linear, aliphatic, and complex functionalized derivatives. The products are readily derivatized into diverse chiral scaffolds, and gram-scale synthesis underscores the practicality of this method.