Biaryls are present in multiple current drugs as well as drug candidates; they have displayed a broad range of therapeutic activities including antifungal, anti-inflammatory, antirheumatic, antitumor, and antihypertensive agents. Therefore, a great deal of effort has been dedicated to the development of efficient methods for their regioselective synthesis. To date, there is no precedent for a catalytic, highly regioselective, an intermolecular direct arylation of simple arenes (arenes lacking activating or directing groups or both) with aryl (pseudo)halides for the synthesis of biaryls in which the reaction occurs with a 1:1 ratio of arene and aryl (pseudo)halide. This proposal outlines a detailed strategy to achieve this objective by developing a cooperative catalytic system which consists of one cycle leading to C-H bond cleavage through the use of a metal pincer complex and a second cycle that is akin to the cycle for palladium-catalyzed cross-couplings of aryl halides or sulfonates. Initial investigation will center on the identification of suitable metal pincer complexes that cleave arene C-H bonds under mild conditions followed by the development of catalytic, regioselective C-H arylations of simple arenes with a stoichiometric amount of an isolated arylpalladium complex obtained by oxidative addition of an aryl (pseudo)halide to palladium (0) species. Mechanistic studies will be conducted to understand factors controlling this new reactivity as well as site-selectivity. Finally, the cooperative catalytic system will be developed by combining an oxidative addition process of aryl (pseudo)halides to a palladium (0) complex with the catalytic C-H activation of simple arenes. Success in the proposed study will provide a practical method for the preparation of medicinally important biaryls as well as new mechanistic insights for further applications in the development of cooperative catalysis that involves site-selective functionalizations of simple arenes.