Organophosphine-catalyzed cycloaddition reaction provides an efficient method for the construction of valuable heterocycles. In this article, density functional theory calculations were performed on the mechanism of a phosphine-catalyzed [4+2] cycloaddition between conjugated dienes and enones reported recently. The overall reaction consisted of four sequential processes, namely the formation of the zwitterionic intermediate, intermolecular nucleophilic addition, intramolecular cyclization, and removal of the organophosphine. The activation free-energy barrier was estimated to be 84.4 kJ/mol, and the overall free-energy change was computed to be –18.8 kJ/mol. For the asymmetric variant of the reaction, the predicted enantioselectivity results were consistent with experimental findings, and what’s more, a distortional strain model was proposed to understand the observed enantioselectivity. Lastly, the substituent effects concerning the diene substrate were explored, which revealed that an ester group on the C(2) position would exert a much stronger influent on the reactivity than that on the C(1) position. The conclusions drawn in this work can help organic chemists to optimize experimental conditions and design new reactions.

Key words: organophosphine catalysis, reaction mechanism, density functional theory, stereoselectivity, substituent effect