Mechanisms and origins of stereoselectivity involved in NHC-catalyzed [3 + 3] Annulation of 2-bromoenals and β-ketothioamides: A DFT study

We reported a density functional theory (M06–2X) study of the possible mechanisms operating in a chemo- and stereoselective [3+3] annulation reaction of 2-bromoenal with β-ketothioamide catalyzed by a chiral NHC catalyst. DFT computations suggest the catalytic reaction involves nucleophilic addition, [1,2]-proton transfer, debromination, [1,3]-proton transfer, Michael addition, [1,5]-proton transfer, ring closure and catalyst dissociation, in which Michael addition is the chemo- and stereoselectivity-determining step and provides the SR-configured sipro-piperidinone predominantly. This result is consistent with the stereoselectivity observed in experiment. Nonconvalent interaction (NCI) analysis reveals that the origin of stereoselectivity is the different weak interactions (C–H···π, LP···π and π···π). The computational results should deepen our understanding of NHC catalysis, and may thus contribute to the design of new catalytic systems.