Investigating Transformations in Catalytic Pathways and Site Selectivity of Pd ₃ Nanocluster-Catalyzed Cross-Coupling Reactions

Atom-precise nanoclusters (NCs) of Pd have emerged as highly active and selective catalytic systems for cross-coupling and hydrogenation reactions. The unique Pd speciation in NCs has enabled unconventional site selectivity in cross-coupling reactions, which is challenging to obtain using mononuclear Pd complexes. However, the mechanism behind the distinct catalytic behavior of NCs in cross-coupling reactions and the influence of reaction conditions on these mechanisms are poorly understood. Herein, the catalytic behavior and speciation evolution of [Pd3(μ-Cl)(μ-PPh2)2(PPh3)3]+ (i.e., Pd3) NCs have been studied in Suzuki–Miyaura cross-coupling reactions using in situ XAS analysis complemented by mass spectrometry. Our results indicate that the Pd3 NCs can catalyze cross-coupling reactions via a homogeneous pathway and show very high site selectivity toward atypical C4-arylation in the cross-coupling reaction between 2,4-dibromopyridine and phenylboronic acid. After extended reaction times (>2 h), the transformation of Pd3 NCs into nanoparticles generates additional heterogeneous catalytic centers in the reaction mixture, which significantly influences the overall outcome of the reaction by switching the site selectivity from C4-arylation to C2-arylation. This further favors a secondary arylation of the C4-arylated product to form a biarylated product. However, the addition of quaternary ammonium hydroxide to the reaction mixture and/or performing the reaction under mild conditions (∼25 °C) provided stability to Pd3 NCs against aggregation, leading to very high C4-arylation selectivity (i.e., ∼70%) throughout the reaction. The quaternary ammonium salts were found to directly interact with the metallic core of the Pd3 NCs, forming another homogeneous intermediate in the reaction mixture. Overall, the results from this work indicate that the use of Pd NCs as catalysts in cross-coupling reactions can provide unusual site selectivity; however, care needs to be taken to ensure their stability in long and large-scale catalytic processes.