Unravelling the mechanism and the origin of the selectivity of the [3+2] cycloaddition reaction between electrophilic nitrone and nucleophilic alkene

In this paper, we have studied within the molecular electron density theory the mechanism and the origin of the selectivity of the [3 + 2] cycloaddition reaction between electrophilic nitrone 1 and nucleophilic alkene, indole 2, using DFT method at the B3LYP/6-31G(d) theoretical level. The obtained results clearly indicated that this reaction is characterised by an ortho regioselectivity and an exo stereoselectivity. Inclusion of the solvent effects does not modify the obtained gas-phase selectivities but slightly increase the activation energies. The analysis of the geometries of the transition states with bond order and global electron density transfer shows that this reaction takes place via a slightly asynchronous non-polar one-step mechanism. Analysis of the electronic structure of nitrone 1 indicates that this species has a zwitterionic-type structure that enables its participation in zw-type 32CA reactions. Conceptual DFT reactivity indices analysis confirms the highly obtained activation energies and local Parr functions analysis allows us to explain the ortho regioselectivity of this 32CA reaction. NCI, ESP and QTAIM analyses indicate that the presence of several conventional and non-conventional interactions at the structure of the most favourable approach ortho-exo is the origin for the selectivity of this 32CA reaction.