Understanding the molecular mechanism in a regiospecific [3+2] cycloaddition reaction including C-O interaction: A MEDT study

Abstract

The [3+2] cycloaddition (32CA) reaction between nitrone and an electronic deficient methyl acetylene carboxylate (MAC) was studied within the Molecular Electron Density Theory (MEDT) by using DFT functional combined with B3LYP and 6-31+(d,p) as a basis set. Conceptual DFT (CDFT) analysis allows to characterize nitrone and MAC as a strong nucleophile and a strong electrophile respectively, while analysis of the Parr functions allows explaining the chemo- and regioselectivity observed experimentally in complete agreement with the barrier activation. Electron localization function (ELF) topological analysis of several points along intrinsic reaction coordinate (IRC) profile associated with the energetically most favorable reaction channel permits to establish a non-concerted two-stage one-step molecular mechanism. The reaction begins by the creation of a pseudoradical center at the terminal carbon, firstly at the methyl acetylene carboxylate derivative (MAC), and secondly at the nitrone framework which immediately promotes the formation of the first O–C single bond by donation of some electron density of oxygen atom lone pairs