Unraveling the Polarization Effect of Sulfur Atom on the Mechanism and Selectivity in the 32CA Involving C–S and C–O Interactions: A Rationalization Study Using Bonding Evolution Theory

Abstract

A defined theoretical study was performed, the mainly factors controlling the preparation of 3-fluoroalkylated 1,4,2-oxathiazoles were completely investigated, to this end, the B3LYP/6–31G(d) computational level within the Molecular Electron Density Theory was employed. A significant predominance of 3-fluoroalkylated 1,4,2-oxathiazoles derivatives (D1) has been generated via [3 + 2] cycloaddition between thioketone and nitrile oxide, rationalized by the electrophilic P+ and nucleophilic P Parr functions at the reactive sites of reagents, affording the S1–C3 regioselectivity observed experimentally. Besides, an investigation of the relative energies of reaction, Gibbs free energy and barrier activation profile clearly evidences that experimentally isolated D1 is the most reachable product of this reaction, both kinetically and thermodynamically. Importantly, the high polarization of C=S bond toward S sulfur atom over O–C bond polarization make it the nitrile oxide more electrophile instead nucleophile. Furthermore, the ELF topological patterns of the most favorable product indicate that the formation of new bonds in the 32CA reaction between thioketone and nitrile oxide will appear through two unrelated manners, the first is formed by coupling of S- to -C pseudoradical center generated at the most significant atom, while the second is formed by sharing nitrogen non-bonding electron-density and a carbon pseudoradical center via a non-concerted two-stage one-step molecular mechanism.