Peri-, Chemo-, Regio-, Stereo- and Enantio-Selectivities of 1,3-dipolar cycloaddition reaction of C,N-Disubstituted nitrones with disubstituted 4-methylene-1,3-oxazol-5(4H)- one: A quantum mechanical study

The peri-, chemo-, regio-, stereo- and enantio-selectivities of 1,3-dipolar cycloaddition reaction of C,N-disubstituted nitrones with disubstituted 4-methylene-1,3-oxazol-5(4H)-one have been studied using density functional theory (DFT) at the M06–2X/6-311G (d,p) level of theory. The 1,3-dipole preferentially adds chemo-selectively across the olefinic bond in a (3 + 2) fashion forming the corresponding spirocycloadduct. The titled reaction occurs with poor enantio- and stereo-selectivities, but a high degree of regio-selectivity is observed for the addition of the 1,3-dipole across the dipolarophile. Electron-withdrawing groups on the dipolarophile significantly reduce the activation barriers while electron-donating groups on the dipolarophile increase the activation barriers. Analysis of the HOMO and LUMO energies of the two reacting species indicates that the 1,3-dipole reacts as a nucleophile while the dipolarophile reacts as the electrophile. Investigation of the electrophilic Parr function (PK+) at the various reaction centers in the dipolarophile indicates that the 1,3-dipole selectively adds across the atomic species with the largest electrophilic Mulliken and NBO atomic spin densities which is in accordance with the energetic trends observed. [Display omitted] •Dipole adds across the dipolarophile to form a heterocyclic ring in a (3 + 2) fashion rather than the (4 + 3) pathway.•The (3 + 2) addition chemo-selectively occurs along the olefinic bond instead of the carbonyl bond.•The reaction proceeds with poor stereo- and enantio-selectivities but high degree of regio-selectively is observed.•EDGs on the dipolarophile increase the activation barriers while EWGs tend to decrease the activation barriers.•Ethanol solvation and temperature has no substantial effect on the observed energetic trends in the gas phase computation.