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 (S E Ar). 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 S E Ar mechanism for the first C−H activation.