Theoretical study on the origin of enantioselectivity in the primary amine–Br?nsted acid catalyzed epoxidation of cyclic enones

摘要

Computational studies to determine the origin of enantioselectivity in the (1R,2R)-1,2-diphenylethane-1,2-diamine (DEPN)–Br?nsted acid catalyzed epoxidation of 2-cyclohexen-1-one have been performed using density functional theory. Transition states for conjugate addition and ring closure steps of the epoxidations catalyzed by three different catalyst systems were characterized. Our calculations show that the C_(sp2)H…O H-bond interaction between the benzene ring of the catalyst and H_2O is mainly responsible for the chiral discrimination observed. The Br?nsted acid counterion plays a very important role in ensuring high enantioselectivity by improving the rigidity of the transition state structures to allow the efficient formation of the C_(sp2)H…O H-bond. Moreover, we explain why these two diamine catalysts (1S,2S)-DACH and (1R,2R)-DPEN display consistent enantioselectivities in the catalytic epoxidation of 2-cyclohexen-1-one when combining with three different cocatalysts; achiral TFA, and chiral (R)- and (S)-TRIP.