Evidence for Suzuki-Miyaura cross-couplings catalyzed by ligated Pd₃-clusters: from cradle to grave

Pd clusters offer unique selectivity and exploitable reactivity in catalysis. Understanding the behavior of Pd clusters is thus critical for catalysis, applied synthetic organic chemistry and greener outcomes for precious Pd. The Pd₃ cluster, [Pd₃(μ-Cl)(μ-PPh₂)₂(PPh₃)₃][Cl] (denoted as Pd₃Cl₂), which exhibits distinctive reactivity, was synthesized and immobilized on a phosphine-functionalized polystyrene resin (denoted as immob-Pd₃Cl₂). The resultant material served as a tool to study closely the role of Pd₃ clusters in a prototypical Suzuki-Miyaura cross-coupling of 4-fluoro-1-bromobenzene and 4-methoxyphenyl boronic acid at varying low Pd ppm concentrations (24, 45, and 68 ppm). Advanced heterogeneity tests such as Hg poisoning and the three-phase test showed that leached mononuclear or nanoparticulate Pd are unlikely to be the major active catalyst species under the reaction conditions tested. EXAFS/XANES analysis from (pre)catalyst and filtered catalysts during and after catalysis has shown the intactness of the triangular structure of the Pd₃X₂ cluster, with exchange of chloride (X) by bromide during catalytic turnover of bromoarene substrate. This finding is further corroborated by treatment of immob-Pd₃Cl₂ after catalyzing the Suzuki-Miyaura reaction with excess PPh₃, which releases the cluster from the polymer support and so permits direct observation of [Pd₃(μ-Br)(μ-PPh₂)₂(PPh₃)₃]⁺ ions by ESI-MS. No evidence is seen for a proposed intermediate in which the bridging halogen on the Pd₃ motif is replaced by an aryl group from the organoboronic acid, i.e. formed by a transmetallation-first process. Our findings taken together indicate that the 'Pd₃X₂' motif is an active catalyst species, which is stabilized by being immobilized, providing a more robust Pd₃ cluster catalyst system. Non-immobilized Pd₃Cl₂ is less stable, as is followed by stepwise XAFS of the non-immobilized Pd₃Cl₂, which gradually changes to a species consistent with 'Pd(PPh₃)' type material. Our findings have far-reaching future implications for Pd₃ cluster involvement in catalysis, showing that immobilization of Pd₃ cluster species offers advantages for rigorous mechanistic examination and applied chemistries.