Activation and Deactivation Strategies Promoted by Medium Effects for Selective Aliphatic C−H Bond Functionalization

Selective functionalization of unactivated aliphatic C−H bonds represents an important goal of modern synthetic chemistry. Differentiating between such bonds in organic molecules with high levels of selectivity remains a crucial issue, and a profound understanding of even the subtlest reactivity trends is needed. Among the methods that have been developed, those based on hydrogen atom transfer (HAT) have attracted considerable interest. Within this framework, medium effects have proved effective in altering the reactivity and site selectivity in synthetically useful C−H functionalization procedures. In this Review, the mechanistic features behind the available strategies are discussed. It is shown that hydrogen bonding and acid–base interactions can promote C−H bond activation or deactivation toward HAT reagents, thereby providing fine-control over the site selectivity and product chemoselectivity as well as useful guidelines for future development and applications.