Diastereoselective Green Synthesis of Pyrrolo[1,2-a]quinolines via [3+2] Cycloaddition Reaction: Insights from Molecular Electron Density Theory

The [3 + 2] cycloaddition (32CA) reaction between cyclic azomethine ylide (generated from N -phenacylquinolinium bromide) and N -arylmaleimide, leading to pyrrolo[1,2-a]quinolone, has been investigated using the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311 + + G(d,p) computational level. This study focuses on the zwitter-ionic type 32CA reaction, highlighting its polar character with the electronic flux from the azomethine ylide to the alkene. The reaction proceeds with complete endo- stereoselectivity, and the activation parameters show minimal variations in different solvents, consistent with experimental observations. The activation energy is associated with the depopulation of the N2-C1 and C4-C5 bonding regions, formation of non-bonding electron density at N2 nitrogen and creation of pseudoradical centers at C3, C4 and C5. These findings suggest that the formation of new covalent bonds does not occur at the transition states, in line with the presence of non-covalent interactions at the interatomic bonding regions, as revealed by the topological analysis of the Quantum Theory of Atoms-in-Molecules (QTAIM).