DFT investigation of the mechanism of E/Z isomerization of nitrones

The hitherto unknown mechanism of E/Z isomerization of nitrones, with important implications in 1,3-dipolar cycloaddition chemistry, has been investigated using density functional theory calculations. Unimolecular and bimolecular processes have also been considered. Both concerted and stepwise mechanisms involving either zwitterionic or diradical species have been studied. The unimolecular torsional mechanism and isomerization through intermediate oxaziridines present energy barriers too high to justify the observed experimental results. Several bimolecular processes involving an initial dimerization are possible. Among them, the concerted process can be discarded in terms of energy barrier. Zwitterionic intermediates are too high in energy to be considered. From the two possible diradical approaches consisting of either C-O or C-C coupling, the latter is the most favored. Thus, the mechanism of E/Z isomerization of nitrones proceeds via a diradical bimolecular process involving an initial dimerization through a C-C coupling followed by a dedimerization, with energy barriers for the rate-limiting step of 29.9 kcal/mol for C-methyl nitrones and 25.8 kcal/mol for C-(methoxycarbonyl) nitrones. These values are in very good agreement with the experimental data previously measured through kinetic experiments.