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

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Elsevier Inc.
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.
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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.