Transient Directing Groups for Transformative C-H Activation by Synergistic Metal Catalysis

The development of methods for the functionalization of otherwise inert C-H bonds is one of the major foci in molecular syntheses. Recent advances have significantly improved the arsenal of synthetic chemistry, enabling the use of less functionalized starting materials, a reduction of energy consumption, and a minimization of waste production. Despite undisputable progress, the main challenge associated with synthetically meaningful C-H activations is achieving positional selectivity. Thus far, the most common approach to address site selectivity in transition-metal-catalyzed intermolecular transformations is constituted by chelation assistance through directing groups. The installation and removal of these directing groups adds additional steps, compromising the step-economical nature of the overall C-H activation strategy. In contrast, here we discuss the emergence of transient directing group approaches through the in situ installation and deconstruction of a Lewis-basic entity with the aid of co-catalytic additives for selective C-H functionalizations.