Mechanism and origins of enantioselectivity of cobalt-catalyzed intermolecular hydroacylation/cyclization of 1,6-enynes with aldehydes

Abstract

Density functional theory calculations were performed to investigate the cobalt-catalyzed intermolecular hydroacylation/cyclization of 1,6-enynes with aldehydes. The computations show that the initial oxidative cyclization constitutes the rate-determining step of the overall reaction. The enantioselectivity is caused by the competition between the oxidative cyclization of the S-pathway and the migratory insertion of the R-pathway. The origins of the enantioselectivity are mainly due to the steric repulsion between the aldehyde moiety and the aryl substituent of the 1,6-enyne.