Mechanistic Insights into ortho-Quinone Methide Cycloadditions with Push-Pull Dienophiles: A Density Functional Theory Study

A detailed theoretical investigation of the mechanism of [4+2]-cycloaddition of o-quinone methides (o-QMs) to push-pull alkenes has been performed using density functional theory at the DFT/B3LYP/6-311G++(2d,2p) level within the polarizable continuum model (PCM). The cycloaddition was shown to proceed predominantly via in situ generation of o-quinone methides followed by an inverse electron-demand Diels–Alder reaction. An asynchronous yet concerted character of the transition state was established (synchronicity parameter Sy = 0.40–0.48), attributed to the high polarity of the reactants. Analysis of global reactivity descriptors (electrophilicity index ω, global electron density transfer GEDT) and transition state geometries confirmed the regioselective formation of chromanes bearing an electron-withdrawing group at the 3-position. The obtained results are consistent with experimental data and enable rational prediction of selectivity in analogous transformations.