Cobalt Catalyzed Enantioselective Reductive Coupling of Imines and Internal Alkynes

Chiral allylic amines hold significant importance as structural components in natural products, pharmaceuticals, and chiral catalysts. In this study, we have delved into cobalt-catalyzed enantioselective reductive coupling of imines with internal alkynes. The key to our success lies in developing a cobalt bisphosphine conglomerate catalyst and utilizing zinc as the electron donor. Our investigations have indicated that an in-situ cobalt(I) catalyst orchestrates the oxidative cyclization of alkynes and imines. Zinc plays a pivotal role in facilitating the transmetallation of the resulting azacobaltacycle. Subsequently, the organozinc intermediate is captured by a proton. Remarkably, the reaction proceeds under mild conditions and accommodates a wide range of substrates. Both symmetric and asymmetric alkyl and aryl alkynes have been successfully coupled with various imines. We have isolated tri- and tetrasubstituted allyl amines in exceptional yields exceeding 89%, with enantiomeric excess surpassing >99% and regioselectivities exceeding >20:1. These chiral allylic amines can serve as versatile platform molecules for subsequent transformations while preserving their stereochemical integrity to a high degree.