Insights into NHC-catalyzed oxidative -C(sp3)-H activation of aliphatic aldehydes and cascade [2+3] cycloaddition with azomethine imines

To predict whether catalysts can work efficiently is one of the most challenging questions in the catalysis field. Herein, we suggested that a Lewis base organocatalyst can promote [2 + 3] cyclization by avoiding the poor frontier molecular orbital (FMO) overlap mode involved in the chemical changes for the first time. Density functional theory (DFT) calculations were performed to disclose the detailed mechanism and origin of stereoselectivity of N-heterocyclic carbene (NHC)-catalyzed oxidative -C(sp(3))-H activation of aliphatic aldehydes and cascade [2 + 3] cycloaddition with azomethine imines. The computational results indicate that the NHC catalyst can significantly lower the energy barrier of the rate- and stereoselectivity-determining [2 + 3] cycloaddition by changing the shoulder-to-head to head-to-head overlap mode to enable the cycloaddition. Therefore, this work would be valuable not only for predicting the efficiency of the organocatalyst in [2 + n] (n = 2, 3, 4) cyclization reactions, but also for developing new applications of FMO theory in the organocatalysis field.