Mechanistic Insight into the Origin of Stereoselectivity in NHC-Catalyzed [3 + 3] Annulation of Enal with Enamine

In this study, the reaction mechanism and the origin of stereoselectivity in the NHC-catalyzed [3 + 3] annulation between an enal and an enamine are thoroughly investigated using density functional theory (DFT) calculations. The acylazolium intermediate plays a pivotal role in the subsequent transformation. Notably, both central and axial chiralities are established during the process. Computational analysis reveals that the nucleophilic attack of the anionic enamine on the acylazolium intermediate dictates the stereoselectivity, favoring the Si–Si addition mode. Furthermore, the underlying mechanism of stereoselectivity is elucidated through activation strain model (ASM) and noncovalent interaction (NCI) analyses. The ASM analysis indicates that noncovalent interactions govern the selectivity, which are specifically identified as LP···π, C–H···π, and hydrogen bonding interactions via NCI and AIM analyses.