Unveiling the high reactivity of benzyne in the formal [3+2] cycloaddition reactions towards thioamides through the Molecular Electron Density Theory

Abstract

AbstractThe domino reaction of benzyne with thioamide has been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d) level. This domino reaction takes place through i) a formal [3 + 2] cycloaddition (32CA) reaction affording an ammonium ylide, and ii) an extrusion of ethylene from this species yielding a dihydrothiazole. Topological analysis of the electron density of benzyne shows its pseudodiradical structure, that is, without any energy cost, changes to a carbenoid one, allowing its participation as electrophile in polar reactions. As a consequence, the formal 32CA reaction does not have an activation enthalpy. Analysis of the changes of electron density along the domino reaction indicates that while the formal 32CA reaction takes place through a two-stage one-step mechanism, the extrusion of ethylene takes place through an intramolecular E2 elimination mechanism. The present MEDT study reveals the chameleonic structure/reactivity of benzyne, allowing its participation in both non-polar and polar reaction with an unappreciable activation enthalpy.