Theoretical study of an N-heterocyclic carbene-catalyzed annulation reaction between an enal and a β-silyl enone: Mechanism and origin of stereoselectivity

In this study, the mechanism and origin of the stereoselectivity of an N-heterocyclic carbene (NHC)-catalyzed transformation reaction between an enal and a β-silyl enone are systematically investigated using density functional theory (DFT) at the M06-2X level. Multiple pathways are proposed and studied to identify the most energetically favorable mechanism for the reaction. The calculation results show that the most energetically favorable pathway comprises the following processes: nucleophilic addition of NHC to the Si-face of the enal to form a zwitterionic intermediate, two sequential CsHCO3-assisted intramolecular proton shifts to produce an enolate intermediate, Michael-type addition of the enolate intermediate to the β-silyl enone, ring closure to construct a six-membered ring intermediate, and the dissociation of NHC to release the final product. The reaction between the enolate intermediate and the β-silyl enone is identified as the stereoselectivity-determining step, preferentially generating an RS-configured product. Subsequent atoms-in-molecules (AIM) and noncovalent interaction (NCI) analyses verify that the main factor for inducing stereoselectivity is the higher number of noncovalent intermolecular interactions in the low-energy transition state.