Theoretical calculational investigation on the regioselectivity of the ring opening of thiiranes with ammonia and amines

The course, especially the regioselectivity, of the nucleophilic ring opening of thiiranes with ammonia and amines was investigated with the density functional theory (DFT) calculation. In the ring-opening reaction, thiiranes could be attacked on either their less or more substituted carbon atoms. The analyses of the potential energy surfaces, the bond lengths, and charges of key species in both pathways indicate that alkyl-substituted thiiranes are attacked dominantly on their less substituted ring carbon atom, whereas arylthiiranes are on their more substituted one due to the existence of the p-π conjugative effect, which stabilizes the transition states generated in the reaction. Furthermore, the Lewis acid can modulate the regioselectivity. However, the steric hindrance of nucleophiles and solvents affect the regioselectivity slightly as they show similar influence on both pathways, despite the fact that they can put an impact on the energy. NBO and MO analyses also support the substituent-depended regioselectivity. This is the first DFT calculational investigation on the regioselective ring opening of thiiranes and provides a rational explanation for the experimental results. The theoretical investigation gives a general understanding and a rule for the rationale and prediction of the regioselectivity in the nucleophilic ring opening of thiiranes, even other three-membered heterocycles.