A computational investigation into the substituent effect on the chemo- and stereoselectivity of crossed intermolecular radical anion [2 + 2] cycloadditions of enones

Abstract

Density functional theory calculations have proven the polar nature of the crossed intermolecular radical anion cycloadditions of various enones. The substituent effects on the chemo- and stereoselectivity of the cycloadditions have been elucidated. The electronic structures of the substituents strongly influence the formation of the radical anion and the reactivity of cycloaddition. The amino and nitryl substituents are both unfavorable for the cycloaddition. The cycloaddition is sensitive to the substituents on the C atoms which form a σ bond in the first cycloaddition step by both steric hindrance and electronic effect. To improve the chemoselectivity, one of these C atoms should be unsubstituted. The stereoselectivity mainly caused by the difference in steric interaction between the trans and cis transition states is benefited by the bulky substituents on the carbonyl.