Theoretical examination on the regioselective ring-opening of substituted aziridines: steric vs. electronic effect

Abstract

Aziridines serve as versatile building blocks for organic synthetic chemistry and play a pivotal role in biologically relevant reactions. Thus, the regioselectivity in aziridine ring-opining reaction is highly important to get a target product. Aziridines usually prefer nucleophilic attack at the less-substituted carbon (C3) due to minimal steric hindrance. Occasionally, however, there are some exceptions where the more-substituted carbon (C2) undergoes nucleophilic attack. In this study, we examined the regioselectivity of aziridine ring-opening with quantum chemical DFT calculation methods including density functional theory [B3LYP/ 6-31+G(d)]. The energy profiles of aziridine ring-opening were obtained, the activation barriers $(\Delta E^‡)$ were compared, and then the regioselectivity was determined. The analysis of reactant properties provided good explanation for regioselectivity. It was demonstrated that the unusual ring-opening occurs along the C2-N bond, activated by the concerted interaction between electron-donating aryl group and electron-withdrawing pyridine moiety.