Steering Site-Selectivity in Transition Metal-Catalyzed C-H Bond Functionalization: the Challenge of Benzanilides

Selective C-H bond functionalization catalyzed by metal complexes have completely revolutionized the way in which chemical synthesis is conceived nowadays. Typically, the reactivity of a transition metal catalyst is the key to control the site-, regio- and/or stereo-selectivity of a C-H bond functionalization. Of particular interests are molecules that contain multiple C-H bonds prone to undergo C-H bond activations with very similar bond dissociation energies at different positions. This is the case of benzanilides, relevant chemical motifs that are found in many useful fine chemicals, in which two C-H sites are present in chemically different aromatic fragments. In the last years, it has been found that depending on the metal catalyst and the reaction conditions, the amide motif might behave as a directing group towards the metal-catalyzed C-H bond activation in the benzamide site or in the anilide site. The impact and the consequences of such subtle control of site-selectivity are herein reviewed with important applications in carbon-carbon and carbon-heteroatom bond forming processes. The mechanisms unraveling these unique transformations are discussed in order to provide a better understanding for future developments in the field of site-selective C-H bond functionalization with transition metal catalysts.