Understanding the regio-and diastereoselective synthesis of a potent antinociceptive isoxazolidine from C-(pyridin-3-yl)-N-phenylnitrone in the light of molecular electron density theory

[3+2] cycloaddition reaction of C -(pyridin-3-yl)- N -phenyl nitrone and 2-propen-1-ol yields stereochemically defined potent antinociceptive isoxazolidine derivative. Computational Quantum calculations (CQC) are performed for this synthesis to predict the polar character, mechanism and selectivity within the framework of molecular electron density theory (MEDT). Topological analysis of the Electron Localization Function (ELF) classifies the nitrone as a zwitter-ionic ( zw- ) type three atom component (TAC) showing absence of any pseudoradical or carbenoid centre. Four reaction channels corresponding to the possible regio- and stereoselective pathways are studied at DFT/B3LYP/6-311G(d,p) level of theory. The reaction follows one-step mechanism with asynchronous transition states and the computed activation energies agree well with experimental data. The reaction can be differentiated into nine ELF topological phases, with faster C-C bond formation. Global electron density theory (GEDT) at the favoured transition state and Conceptual Density Functional Theory (CDFT) indices at the ground state of the reagents indicate non-polar character. Non-covalent interactions are predicted by Atoms-in-molecules (AIM) analysis and non-covalent interaction (NCI) plots at the transition states.