Transition-Metal-Catalyzed Asymmetric Benzylic Substitutions Through η³-Benzyl-Metal Intermediates

Although transition-metal-catalyzed asymmetric benzylic substitution is conceptually analogous to asymmetric allylic substitution, proceeding via η³-benzyl-metal and η³-allyl-metal intermediates, respectively, the development of the former, involving benzylic electrophiles, has received comparatively less attention within the synthetic community. This limited progress is largely attributed to the low reactivity of benzylic electrophiles and the associated challenge in achieving stereoselective control. Over the past several decades, different catalytic strategies, such as single metal catalysis, bimetallic catalysis, metal/organo catalysis, and ternary catalysis, have been developed to address these challenges. Asymmetric versions of these transformations have also been established, enabling the construction of stereocenters either at the benzylic electrophiles, at nucleophile, or simultaneously at both sites. This review provides a comprehensive overview of this field from its inception to the present. It summarizes advances in substrate scope, mechanistic understanding, synthetic applications, and remaining challenges, with the aim of fostering further progress in this emerging area.