The electronic effects of Lewis acids (LAs) in nucleophilic substitution (SN) reactions are investigated from a molecular electron density theory (MEDT) perspective at the ωB97X-D/6-311G(d,p) level in dichloromethane. The LA-catalyzed ring-opening of two sulfonyl aziridines, typically classified as SN2-type processes, is analyzed, and the LA-assisted SN reactions of three N-alkylmethanesulfonamides toward the chloride anion. LAs do not significantly increase the electrophilicity ω of the substrate but markedly enhance the nucleofugality Λ of the sulfonamide-leaving group (LG), which governs SN feasibility. LAs lower activation enthalpies by over 17 kcal·mol-1, rendering the ring-opening of 2-phenylaziridines fully regioselective. Electron-density topological analyses show that at the transition-state structures (TSs), the C-N bond associated with the LG is already broken, whereas C-Cl bond formation has not begun, indicating a carbocation-like structure at the central carbon. A relative interacting atomic energy analysis of the LA-catalyzed ring-opening of 1-methanesulfonylaziridine by the chloride anion in the presence of Me4N+ reveals that stabilization of both the sulfonamide:LA LG and chloride accounts for the reduced activation barriers. LAs such as BF3 and AlCl3 enhance the LG ability (nucleofugality Λ) of sulfonamides, shifting the TS toward a more carbocation-like (SN1-like) structure and lowering the nucleophile participation.
Domingo et al. (2026) studied this question.