Site-selective dihalogenated heteroarene cross-coupling with organometallic reagents usually occurs at the halogen proximal to the heteroatom, enabled by intrinsic relative electrophilicity, particularly in strongly polarized systems. An archetypical example is the Suzuki–Miyaura cross-coupling (SMCC) of 2,4-dibromopyridine with organoboron species, which typically exhibit C2-arylation site-selectivity using mononuclear Pd (pre)­catalysts. Given that Pd speciation, particularly aggregation, is known to lead to the formation of catalytically competent multinuclear Pd n species, the influence of these species on cross-coupling site-selectivity remains largely unknown. Herein, we disclose that multinuclear Pd species, in the form of Pd3-type clusters and nanoparticles, switch arylation site-selectivity from C2 to C4, in 2,4-dibromopyridine cross-couplings with both organoboronic acids (SMCC reactions) and Grignard reagents (Kumada-type reactions). The Pd/ligand ratio and the presence of suitable stabilizing salts were found to be critically important in switching the site-selectivity. More generally, this study provides experimental evidence that aggregated Pd catalyst species not only are catalytically competent but also alter reaction outcomes through changes in product selectivity.

Agarose-supported copper nanoparticles (CuNPs@agarose) were prepared by immobilization of copper bromide on agarose followed by in situ chemical reduction. The new material was characterized by SEM, EDX, TEM, TGA, XRD, nitrogen adsorption–desorption, and solid UV–vis analysis. The catalytic activity of CuNPs@agarose was assessed in the three component click synthesis of 1,2,3-triazoles in water under low catalyst loading and mild reaction conditions. The easy synthesis and air-stable catalyst was recycled for five runs with small drops in catalytic activity.

Palladium nanoparticles supported on agarose functionalized Fe3O4 catalyzed C–C bond formation reactions.

Tripalladium clusters of the type [Pd 3 (PPh 3 ) 4 ] 2+ , wherein three linearly connected Pd atoms are stabilized by phosphine and arsine ligands, have been detected and isolated as intermediates during the reduction of well-defined mononuclear [Pd(OTf) 2 (XPh 3 ) 2 ] (X = P and X = As, respectively) to Pd nanoparticles (PdNPs). The isolated [Pd 3 (PPh 3 ) 4 ] 2+ cluster isomerizes on broad-band UV irradiation to form an unexpected photoisomer, produced by a remarkable change in conformation at one of the bridging PPh 3 ligands. A catalytic role for these [Pd 3 (XPh 3 ) 4 ] 2+ species is exemplified in Suzuki−Miyaura crosscoupling (SMCC) reactions, with high activity seen in the arylation of a brominated heterocyclic 2-pyrone. Use of the [Pd 3 (PPh 3 ) 4 ] 2+ cluster enables a switch in site selectivity for SMCC reactions involving 2,4-dibromopyridine from the typical C2bromide site (seen previously for mononuclear Pd catalysts) to the atypical C4-bromide site, thereby mirroring recently reported cyclic Pd 3 clusters and PdNPs. We have further determined that the thermal isomer and photoisomer of [Pd 3 (PPh 3 ) 4 ] 2+ are similarly catalytically active in the Pd-catalyzed hydrogenation of phenylacetylene to give styrene. Our findings link the evolution of mononuclear Pd(II) salts to PdNPs via the intermediacy of linear [Pd 3 (XPh 3 ) 4 ] 2+ clusters.