Advances in Palladium-Catalyzed C(sp3)–H Functionalization: The Role of Traceless Directing Groups

Selective functionalization of a specific C(sp³)–H bond remains an open challenge in synthetic chemistry. One common strategy employed by chemists to address this challenge is the use of directing groups to select and break a particular C(sp³)–H bond. There are various types of directing groups, classified based on their roles during the reaction, such as removable, nonremovable, transient, and traceless directing groups (TDGs). Among them, TDGs including −I, −Br, −OTf, −ONf, and −COOH have been explored for C(sp³)–H functionalization using different catalysts. Palladium is one of the widely used catalysts for the functionalization of C(sp³)–H via TDGs, and Pd(OAc)₂ is the most commonly used palladium complex in these reactions. Palladium can form a palladacycle intermediate (usually a five-membered ring) to facilitate the activation and functionalization of target C(sp³)–H bonds, which is often crucial in these transformations. Literature review indicates that palladium-catalyzed C–H functionalization via TDGs has been successfully applied for the formation of several bonds, including C–C, C–N, C–B, and C–P bonds. This Review discusses palladium-catalyzed protocols, in which a TDG is employed to guide the palladium catalyst in activating and functionalizing desired C(sp³)–H bonds.