Intramolecular cyclization reaction mechanism and regioselectivities of unsubstituted and benzene-substituted 4-penteniminyl radicals: A DFT investigation

The cyclization mechanisms and regioselectivities of 4-penteniminyl and benzene-substituted 4-penteniminyl radicals were investigated systematically by density functional theory method and Marcus theory. For the 4-penteniminyl radical, the 5-exo-trig cyclization via a boat-like transition state was found to be the dominant pathway, whereas for the benzene-substituted 4-penteniminyl ring closure processes the 6-endo-trig is the favorable reaction mode. The preferred 5-exo-trig over 6-endo-trig in 4-penteniminyl radical cyclization is believed to come from a stereoelectronic effect and can be elucidated by orbital interactions between HOMO of iminyl radical and FMO of unsaturated CC double bond in the transition state models. The Marcus theory analysis demonstrated that the surprising regiochemistry of benzene-substituted 4-penteniminyl radical cyclization can be attributed to a thermodynamic effect. The extremely high thermodynamic stability of 6-endo-trig product radical resulting from strong p–π delocalization of unpaired electron in benzene ring leads to a significant decrease in reaction activation energy, and further makes the reaction regioselectivity reverse dramatically relative to the unsubstituted system. Therefore, the kinetic and thermodynamic effects dominate the regioselectivities of 4-penteniminyl and benzene-substituted 4-penteniminyl radical cyclization reactions, respectively.