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

Publication date: Available online 21 January 2020Source: Journal of Molecular Graphics and ModellingAuthor(s): George Baffour Pipim, Ernest Opoku, Richard Tia, Evans AdeiAbstractThe 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.Graphical abstract
Source: Journal of Molecular Graphics and Modelling - Category: Molecular Biology Source Type: research