Unveiling the mechanism and regioselectivity of the [3+2] cycloaddition reaction between N-methylphenylnitrone and 1-sulphonyl-1-trifluoromethylallene. A MEDT study

The present study reports within the molecular electron density theory the mechanism and the selectivity of the [3 + 2] cycloaddition (32CA) reaction between an N-methyl-phenylnitrone (nitrone 5) toward the poorest electrophile1-sulphonyl-1-trifluoromethylallene (allene 6) using DFT method at the B3LYP/6-31G(d) theoretical level. Four reactive pathways associated with the ortho and meta regioselective channels and endo and exo stereoselective approaches modes have been explored and characterised. While the formation of the meta/exo cycloadduct as the major isomer proceeds via a stepwise mechanism with the participation of zwitterion intermediate. Whereas, the other three pathways follow a one-step mechanism, the conceptual DFT reactivity indices analysis explains correctly the polar character of this 32CA reaction, and the local Parr functions analysis enables us to explain the meta-regioselectivity observed experimentally. The presence of both trifluromethyl and sulphonyl as electron-withdrawing groups increase markedly the reactivity of the allene and produces the meta selectivity. The inclusion of the solvent effects does not modify the obtained gas-phase selectivities but slightly increases the activation energies as well as the meta-exo stereoselectivity. QTAIM analyse reveal that the presence of significant numbers of conventional and non-conventional interactions at both TSs of the most favourable meta channel is responsible for the complete regioselectivity observed experimentally at this 32CA reaction.