Concerted metalation-deprotonation (CMD) is a mechanistic pathway through which transition-metal catalyzed C–H activation reactions can take place. In a CMD pathway, the C–H bond of the substrate is cleaved and the new C–Metal bond forms through a single transition state. This process does not go through a metal species that is bound to the cleaved hydrogen atom. Instead, a carboxylate or carbonate base deprotonates the substrate. The first proposal of a concerted metalation deprotonation pathway was by S. Winstein and T. G. Traylor in 1955 for the acetolysis of diphenylmercury. It was found to be the lowest energy transition state in a number of computational studies, was experimentally confirmed through NMR experiments, and has been hypothesized to occur in mechanistic studies.
While there are a number of different possible mechanisms for C–H activation, a CMD pathway is common for high valent, late transition metals like Pd, Rh, Ir, and Ru. The C–H bonds that have been found to undergo C–H activation through CMD include those that are aryl, alkyl, and alkenyl. Investigations into CMD paved the way for the development of many new C–H functionalization reactions, especially in the areas of direct arylation and alkylation by palladium and ruthenium.