Peri-, Chemo-, Regio-, Stereo- and Enantio-Selectivities of 1,3-dipolarcycloaddition reaction of C,N-Disubstituted nitrones withdisubstituted 4-methylene-1,3-oxazol-5(4H)- one: A quantummechanical 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 usingdensity functional theory (DFT) at the M06e2X/6-311G (d,p) level of theory. The 1,3-dipole preferentiallyadds chemo-selectively across the olefinic bond in a (3þ2) fashion forming the corresponding spi-rocycloadduct. The titled reaction occurs with poor enantio- and stereo-selectivities, but a high degree ofregio-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 andLUMO energies of the two reacting species indicates that the 1,3-dipole reacts as a nucleophile while thedipolarophile reacts as the electrophile. Investigation of the electrophilic Parr function (PþKÞat the variousreaction centers in the dipolarophile indicates that the 1,3-dipole selectively adds across the atomicspecies with the largest electrophilic Mulliken and NBO atomic spin densities which is in accordancewith the energetic trends observed.
An article published by Elsevier Inc. and also available at https://doi.org/10.1016/j.jmgm.2020.107542
Density functional theory, 1,3-Dipole, Dipolarophile, 4-Methylene-1,3-oxazol-5(4H)-One, Spirocycloadduct
G.B. Pipim et al. / Journal of Molecular Graphics and Modelling 97 (2020) 107542. https://doi.org/10.1016/j.jmgm.2020.107542