Initiation of Palladium Precatalysts: Efficiency and Product Selectivity as a Function of Ligand, Substrate, and Reaction Conditions

This article describes a detailed interrogation of the initiation step (reduction of Pd^II to Pd⁰) for Buchwald’s G3 palladium precatalysts and derivatives thereof. These studies demonstrate that under Suzuki–Miyaura cross-coupling conditions, the cyclometalated Pd^II complexes initiate to form a mixture of two organic products: carbazole (via intramolecular C(sp²)–N coupling) and biaryl (via intermolecular C(sp²)–C(sp²) coupling with the arylboronic acid substrate). The overall yield and rate of initiation, as well as the organic product ratio, vary dramatically as a function of the phosphine ligand, base, solvent, and boronic acid structure. Implications of these results for catalysis are discussed, and the findings are applied to a different class of cyclometalated precatalysts. Overall, this work shows that precatalyst activation is highly condition-dependent and that this step should be a key consideration in the optimization of Pd-catalyzed cross-coupling reactions.