The Dual Effect of the Acetate Ligand on the Mechanism of the Pd-Catalyzed C-H/C-H Coupling of Benzene

Pd(II)carboxylates have emerged as potent catalysts for the direct coupling of (hetero)aromatics, enabling a two-fold C-H activation with various oxidants. Yet, prior research on the mechanism of the C-H/C-H coupling without directing group(s) has led to contrasting insights. In this work, a direct effect of acetic acid (AcOH) concentration on the mechanism of Pd-catalyzed benzene coupling to biphenyl is uncovered. The catalytic cycle was investigated via kinetic isotope effects, H/D exchange experiments and by assessing the reactivity of the Pd(aryl)-intermediates. The study revealed that the catalytic reaction makes a transition between two dissimilar C-H activation steps: a "concerted metalation-deprotonation" (CMD) mechanism followed by an electrophilic substitution (SEAr). A dual role of the acetate ligand explains the transition between these mechanisms, mediating the deprotonation via CMD and coordinating on the Pd(II) ion to preclude a SEAr mechanism for the first C-H activation.