Synergistic combinations of transient directing groups and 3d transition metal catalysis for C-H functionalization.

The transient directing group (TDG) strategy enables site-selective C-H functionalization without the need to install and remove covalent directing groups. Combining TDGs with cost-effective 3d transition metals such as Cu, Ni, Co, and Mn offers both step/atom economy and sustainability, making this an attractive approach for synthetic organic chemistry. Recent years have seen rapid progress in TDG/3d transition-metal systems, leading to diverse C-H functionalizations, including sulfonylation, thiolation, alkynylation, amidation, etherification, halogenation, deuteration, and annulation of aromatic aldehydes and benzylamines. This review summarizes recent advances in this area, categorized by the metal catalyst, with discussion of reaction types, catalytic systems, substrate scope, and mechanisms. Applications in constructing nitrogen-containing heterocycles and late-stage modification of drug molecules are highlighted. Current challenges, such as limited reaction types, harsh conditions, a lack of enantioselective transformations, and the underdeveloped nature of C(sp3)-H functionalization, are discussed, along with future directions including milder reaction conditions, asymmetric catalysis, and the development of new reactions.