Experimental and DFT Studies for Substituent Effects on Cycloadditions of C,N-Disubstituted Nitrones to Cinnamoyl Piperidine

Abstract

Cycloaddition reactions of C-aryl-N-methyl nitrones (with varied electron demand character) to cinnamoyl piperidines have been studied by both experimental and theoretical approaches. The reactions are completely regioselective. Endo/meta selectivity of the major isomer has been confirmed on the basis of UV-Vis, IR, NMR and X-ray studies. Global properties of the reactants have been analyzed. Delocalization and activation energies of the located transition states have been calculated. Concerted mechanism of the reactions has been confirmed from trajectory simulations. Computational studies have rationalized the preferred endo stereoselectivity and have also indicated that increase in electron withdrawing character of nitrone C-aryl substituent decreases the activation energies and increases the diastereomeric excess along the reaction pathway.