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

An intramolecular hydrogen bond-promoted activation of imines represents a new strategy in annulation re-actions catalyzed by N-heterocyclic carbenes (NHCs). In this study, the mechanism and the origin of stereo-selectivity 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 C-H center dot & nbsp;center dot & nbsp;center dot & nbsp;pi, C-H center dot & nbsp;center dot & nbsp;center dot O, pi center dot & nbsp;center dot & nbsp;center dot pi, and lone pair (LP)center dot & nbsp;center dot & nbsp;center dot pi interactions contribute significantly to stabilizing the lower-energy transition state, thus inducing to the pref-erential formation of the RS-configured product.

Automated summary

This study reveals the mechanism and stereo-selectivity origin of NHC-catalyzed annulation of enals and imines through theoretical calculations. The presence of intramolecular hydrogen bond is crucial for the reaction, and non-covalent interaction analysis shows the bonding modes in the lower-energy transition state.