Internally Directed Stereochemical Alteration of Alkene Dihalogenation

Abstract

Electrophilic dihalogenation of alkenes is a powerful strategy for the construction of configurationally defined vicinal dihalides. However, because of its inherent anti-stereospecificity, the practical synthetic access has been largely restricted to only half of the diastereochemical space. Although recent advances enabled complementary syn-dihalogenations through sequences involving anti-addition followed by stereoinversion, these approaches often suffer from limitations when applied to aryl-substituted alkenes that are prone to loss of stereochemical integrity during electrophilic activation via stable benzylic cation formation. Our group previously reported an efficient syn-dichlorination of N-protected allylic amines by exploiting an internal assistance mechanism of a systematically identified stereodirecting group, which notably accommodated aryl alkenes. We present here a full account describing the detailed course of our study, including further efforts to expand the substrate and halogen scopes.