Reactivity and Regioselectivity of Palladium-Catalyzed Direct Arylation in Noncooperative and Cooperative Processes

Recent discovery (J. Am. Chem. Soc 2012, 134, 3683) of the involvement of the cyclometalated [Pd ((Bu2PCMe2CH2)-Bu-t)(OAc)](2) complex in direct arylation of pyridine N-oxide suggested that the mechanism of this reaction may involve a process in which C-H activation occurs at one Pd center and the aryl group undergoes coupling with another aryl group at a second Pd center (a cooperative catalysis). In this work, cleavage of arene C-H bonds of different (hetero)arenes via a concerted metalation-deprotonation (CMD) pathway was evaluated for both noncooperative and cooperative processes so that the two processes could be compared in terms of reactivity and regioselectivity. The distortion-interaction analysis was performed to quantify the various contributions to the CMD transition states. Calculated barriers of the C-H bond cleavage in the two processes indicate that the cooperative and noncooperative processes lead to the same regioselectivity of arylation. Differences in contributions to the activation barriers between the two processes are fairly minor. This allows us to use the existing data about (hetero)arene C-H reactivity and regioselectivity in the noncooperative arylation and apply it to predict reactivity and regioselectivity of arylation in the cooperative process.