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 PdII to Pd0) for Buchwald’s
G3 palladium precatalysts and derivatives thereof. These studies demonstrate
that under Suzuki–Miyaura cross-coupling conditions, the cyclometalated
PdII 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.