Pentanidium-Catalyzed Asymmetric Phase-Transfer Conjugate Addition: Prediction of Stereoselectivity via DFT Calculations and Docking Sampling of Transition States, and Origin of Stereoselectivity

Density functional theory (DFT) study, at the M06-2X/6-311_G(d,p)//M06-2X/6-31G(d,p) level, was carried out to examine the catalytic mechanism and origin of stereoselectivity of pentanidium-catalyzed asymmetric phase-transfer conjugate addition. We employed a hybrid approach by combining automated conformation generation through molecular docking followed by subsequent DFT calculation to locate various possible transition states for the enantioselective conjugate addition. The calculated enantioselectivity (enantiomeric excess), based on the key diastereomeric C-C bond-forming transition states, is in good accord with experimental result. Non-covalent interaction analysis of the key transition states reveals extensive non-covalent interactions, including aromatic interactions, hydrogen bonds, and non-classical C-H center dot center dot center dot O interactions between the pentanidium catalyst and substrates. The origin of stereoselectivity was analysed using a strain-interaction model.