Origin of Regio‐ and Stereoselectivity in the NHC‐catalyzed Reaction of Alkyl Pyridinium with Aliphatic Enal

The mechanisms of N‐heterocyclic carbene (NHC)‐catalyzed dearomatization reaction of alkyl pyridinium have been intensively studied using the density functional theory (DFT) method. The chemoselectivity and stereoselectivity were both analyzed based on the established mechanisms. The computational results showed that the chemoselective C4‐addition occurred before the C2‐addition, which is mainly because the C4 atom was more reactive according to the local reactivity analysis. The stereoselectivity was also investigated, and the C−C bond formation step was identified as the stereoselectivity‐determining step. The C−H⋅⋅⋅F and O−H⋅⋅⋅N interactions are identified as the main factors that govern the stereoselectivity by NCI analysis, and the preferred product was the RS‐configuration. This theoretical investigation would provide a case for understanding and predicting the selectivity of the organocatalytic dearomatization reactions of alkyl pyridinium. Organocatalysis: The mechanisms of NHC‐catalyzed dearomatization reaction of alkyl pyridinium have been studied by using DFT methods. The potential active sites are successfully predicted by using local reactivity index and the origin of stereoselectivity is disclosed by NCI analysis. This theoretical investigation would aid the understanding and prediction of the selectivity of the organocatalytic dearomatization reactions of alkyl pyridinium.