The role of the trifluoromethyl group in reactivity and selectivity in polar cycloaddition reactions. A DFT study

The role of the trifluoromethyl group in reactivity, regio-, and stereoselectivity in cycloaddition reactions has been analyzed by studying the 1,3-dipolar cycloaddition (13DC) reactions of nitrone 4 with 3,3,3-trifluoro-1-nitropropene 7b and 3,3,3-trifluoro-2-nitropropene 14 using density functional theory (DFT) methods at the B3LYP/6-311G(d) level. The recent M06-2X functional has also been evaluated but, although the thermodynamic performance is improved, the kinetic data are not necessarily better than those obtained by the popular B3LYP functional for cycloaddition reactions. Four reactive channels associated with the meta and ortho regio- and endo and exo stereoselective approach modes of the nitro group of these disubstituted ethylenes relative to nitrone 4 have been explored and characterized. Unlike other electron-withdrawing groups, the trifluoromethyl group increases the reactivity of the nitroethylene, but it does not modify the meta and endo selectivities when it is located at the β conjugated position of nitroethylene. Analysis of the global and local electrophilicity indices allows for an explanation of the role of the trifluoromethyl group in reactivity and regioselectivity of electrophilically activated ethylenes.