Unraveling the mechanism and substituent effects on the N-heterocyclic carbene-catalyzed transformation reaction of enals and imines

Abstract

An intramolecular hydrogen bond-promoted activation of imines represents a new strategy in annulation reactions catalyzed by N-heterocyclic carbenes (NHCs). In this study, the mechanism and the origin of stereoselectivity in the NHC-catalyzed annulation of enals and imines are suggested and investigated theoretically. The computational results show that the reaction between a Breslow intermediate and an intramolecular hydrogen bond-activated imine is the rate- and stereoselectivity-determining step and results in the preferential generation of RS-configured products. The presence of intramolecular hydrogen bond is crucial for the reaction, because the formation of such bond significantly enhances the electrophilicity of the imine and thus facilitate the reaction. Non-covalent interaction (NCI) analysis shows that the CH•••π, CH•••O, π•••π, and lone pair (LP)•••π interactions contribute significantly to stabilizing the lower-energy transition state, thus inducing to the preferential formation of the RS-configured product.