Unveiling the reaction mechanism and the regioselectivity of Diels–Alder cycloadditions between 2-methoxy-3-thiophenylbutadiene and methyl vinyl ketone using topological tools

Abstract

The [4 + 2] Diels–Alder cycloaddition reaction between 2-methoxy-3-thiophenylbutadiene 1 and methyl vinyl ketone 2 has been studied at the density functional theory level using a panoply of tools to unravel the regioselectivity and the reaction mechanisms. From the analysis of the CDFT reactivity indices, 2 behaves as an electrophile, while 1 behaves as a nucleophile. This cycloaddition is characterized by a non-polar character as evaluated by a low value of the electrophilicity difference between the reactants as well as a low value of the global electron density transfer at the transition state. Futher, the bonding evolution theory shows that this reaction takes place via a one-step asynchronous mechanism. QTAIM descriptors also highlight the asynchronicity, which confirms the absence of the formation of a new covalent bond. Generally, the ortho/endo pathway is both thermodynamically and kinetically favored over the other routes as revealed by the Distortion/Interaction-Activation Strain (DIAS) analysis, which shows that this preference is primarily driven by differences in interaction energies.