Cobalt‐Catalyzed Enantioselective Reductive Coupling of Imines and Internal Alkynes

Abstract Chiral allylamines are important structural components in natural products, pharmaceuticals, and chiral catalysts. Herein, we report a cobalt‐catalyzed enantioselective reductive coupling of imines with internal alkynes to synthesize chiral allylamines. The reaction is catalyzed by a cobalt complex derived from commercially available bisphosphine ligand utilizing zinc as the electron donor. The substrate scope is extensive. Symmetric and unsymmetric alkyl and aryl alkynes have been successfully coupled with various imines derived from aryl and alkyl aldehydes. Tri‐ and tetra‐substituted allyl amines were isolated in high yields, with enantiomeric excess surpassing >99.9 % and regioselectivities exceeding >20 : 1. These chiral allyl amines can serve as versatile platforms for subsequent transformations while preserving their stereochemical integrity. Extensive experimental and computational mechanistic studies were performed to elucidate the mechanism. These investigations have indicated that an in situ cobalt(I) catalyst enables the oxidative cyclization of alkynes and imines, and a spin crossover occurs during the enantio‐determining step. Zinc plays a pivotal role in facilitating the transmetallation of the resulting azacobaltacycle. The observed enantioselectivity was interpreted by the stabilization of the transition state through higher stabilizing interaction energy from high negative polarization, dispersion, and C−H⋅⋅⋅π interactions.