Density functional theory study of the regio and stereoselectivity in 1,3-dipolar cycloddition reactions between N-methyl methylenenitrone and fluorinated dipolarophiles

Abstract

A DFT study of the reactivity, regio-, and stereoselectivity of 1,3-dipolar cycloaddition of N-methyl-methylenenitrone 1 with (E and Z)-2,4-diethoxy-5-(perfluoroprop-1-en-1-yl)pyrimidine 2E, 2Z and (E and Z)-(perfluoroprop-1-en-1-yl)benzene, 3E, 3Z in the gas phase and in toluene, has been carried out by using density functional theory (DFT)-based reactivity indices and activation energy calculations at B3LYP/6-31G (d) level of theory. Four reactive channels associated with the 5- and 4-regio and endo and exo stereoselective approach modes of the pyrimidine or phenyl group of these fluorinated vinyls relative to nitrone 1 have been explored and characterized. IRC calculations show that these cycloadditions follow an asynchronous concerted mechanism with a low polar character, displaying 5-regioselectivity and it is found that the endo pathway is preferred, therefore the formation of product with 5-regio and endo pathway is dominant. Also, DFT-based reactivity indices clearly predict the experimental regiochemistry.