Exploring the factors controlling the mechanism and the high stereoselectivity of the polar [3+2] cycloaddition reaction of the N,N'-cyclic azomethine imine with 3-nitro-2-phenyl-2H-chromene. A molecular electron density theory study

A molecular electron density theory study of the [3+2] cycloaddition reaction of 5-oxo-2-(phenylmethylidene)pyrazolidin-2-ium-1-ide, a simple azomethine imine, with 3-nitro-2-phenyl-2H-chromene was carried out at the B3LYP/6-311G(d,p) computational level in order to unravel the origin of the stereoselectivity experimentally observed. Electron localization function and natural population analysis showed that the azomethine imine is a zwitterionic three-atom component. Analysis of the conceptual density functional theory reactivity indices indicates that azomethine imine is a strong nucleophile, while 3-nitro-2-phenyl-2H-chromene is a good electrophile, which accounts for a polar process confirmed by the high global electron density transfer values. The Parr function indices explain well the experimentally obtained ortho regioselectivity. Analysis of the energy profiles of the possible reactive pathways in gas phase and in solution of i-PrOH points to high exo stereoselectivity and complete ortho regioselectivity of the reaction in excellent agreement with the experimental findings. Analysis of the transition state structures indicates a very asynchronous molecular mechanism for the favored orthoregioisomeric reaction channels. Analysis using noncovalent interactions, quantum theory of atoms in molecules, and independent gradient model based on Hirshfeld distribution indicates that the presence of several hydrogen bonds and van der Waals intermolecular noncovalent interactions are the factors favoring the ortho-exo selectivity. The bonding evolution theory study of the most favorable pathway reveals a two-stage one-step molecular mechanism.