Heterogeneous (supported) palladium catalysts like palladium on carbon and a variety of metal oxides have been shown to be highly active for Suzuki coupling reactions in neat water under mild reaction conditions (T=65 °C). It has been demonstrated for the first time that hydrophobic effects of the catalyst surface play an important role for the catalyst activity in water. Catalysts possessing hydrophobic surfaces (e.g., palladium on carbon) show higher activity for Suzuki coupling reactions in water than their hydrophilic counterparts (palladium on metal oxides). Tuning of the surface polarity of metal oxide supports (by silylation) results in higher activity under these conditions. Stronger alkaline conditions (three-fold excess of base) compensate the effect of hydrophobic supports and result in high activity of the catalysts also with hydrophilic supports. The addition of tetrabutylammonium bromide to generate, activate and stabilize the catalytic species (dissolved palladium complexes) is necessary for the conversion of more demanding substrates. The reaction is considered to be homogeneous taking place near the catalyst surface inside a droplet or layer of the reactant.

Stabilization of palladium species against agglomeration is essential for reasonable catalytic activity in CC coupling reactions. In contrast to common methods of palladium(0) complex or particle stabilization, a new concept is introduced here: it is demonstrated that a controlled release of palladium from an inactive precatalyst provides stability, too, and leads to high catalytic activity. This paper presents surprising catalytic results for Heck and Suzuki reactions with aryl chlorides and bromides, using three highly stable macrocyclic palladium complexes as catalyst precursors. Three different behaviour patterns for the macrocyclic complexes can be deduced from the evaluation of catalytic activities, UV-Vis spectroscopy, recycling studies of immobilized complexes, and ligand addition experiments. (i) Palladium tetraphenylporphyrin reversibly releases only extremely low amounts of palladium during the reactions, and low coupling activities are observed. (ii) Release of palladium from its phthalocyanine complex is irreversible; cumulative release of palladium into the reaction mixtures leads to high catalytic activity. (iii) Extraordinary results were obtained with a Robson-type complex of palladium, which reversibly releases effectual amounts of palladium into solution under reaction conditions. This controlled release prevents the formation of inactive palladium agglomerates under harsh conditions and leads to high catalytic performances. Even strongly deactivated electron-rich aryl chlorides (4-chloroanisole) can be completely and selectively converted by the in situ formed anionic palladium halide complexes; the addition of typical stabilizing additives (TBAB) was found to be unnecessary. The bimetallic palladium complex is regenerated at the end of the reaction. These results contribute to the current understanding of the active species in CC coupling reactions of Heck and Suzuki types.

Irradiation with light (UV and visible) increases the rate of the Heck reaction using homogeneous (palladium(II) acetate) and heterogeneous (Pd/Al₂O₃ and Pd/TiO₂) catalysts. The rate of the coupling of bromobenzene, chlorobenzene, and 4-chloroacetophenone with styrene was increased under light irradiation at temperatures between 90 and 160 °C. Detailed investigations showed that light irradiation accelerates the reduction of the Pd^II precursor, as confirmed by ³¹P NMR spectroscopy, in which the in situ reduction of [Pd(OAc)₂(PPh₃)₂] to [Pd(PPh₃)_n] (n=2–4) in the presence of PPh₃ took only minutes under visible light irradiation and several hours in the dark. The role of light is, however, complex since it also influences other Pd^II reduction steps in conjunction with catalyst deactivation (Pd black formation). ³¹P NMR spectroscopy showed the same active species, anionic palladium halide complexes, in both irradiated and unirradiated reactions. UV/Vis absorption spectroscopy of Pd(OAc)₂ and DFT calculations, theoretical UV/Vis spectra, and orbital calculations of [PdI₄]²⁻, [PdBr₄]²⁻, and [PdCl₄]²⁻, showed that ligand-to-metal charge transfer (LMCT) is responsible for the accelerated reduction of Pd^II to Pd⁰ under light irradiation.

In order to control the interaction of palladium species with oxide supports, a sol-gel coprecipitation synthesis has been developed for Pd/MO_x. The resulting Pd/MO_x catalysts are characterized by a rather strong interaction between the highly dispersed Pd²⁺ species and the alumina and silica lattices. During coupling reactions of the Heck type the catalytically active species is generated by partial dissolution of Pd from the support surface. Due to the strong bonding of Pd to the support this dissolution occurs to significant extent only at comparatively high temperatures (≥160 °C). These temperatures are exactly necessary for the activation of less-reactive substrates like bromobenzene and aryl chlorides. In this way we are able to synthesize supported catalysts that facilitate a controlled release of soluble Pd species under reaction conditions that are required for the activation of aryl bromides and chlorides. The Pd/MO_x catalysts show excellent activity in the Heck reaction of bromobenzene (TON up to 10000; TOF up to 5000 h^–1) and 4-chloroacetophenone (TON up to 9300; TOF up to 1550 h^–1).(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Palladium on metal oxides and on activated carbon with particular properties (high palladium dispersion, low degree of reduction, water content) are shown to be highly active (tunrover number, TON=20,000; turnover frequency, TOF=16,600), selective and robust catalysts for Suzuki cross-couplings of aryl bromides and activated aryl chlorides. Catalysts and reaction protocol offer combined advantages of high catalytic efficiency under ambient conditions (air and moisture), easy separation and reuse and quantitative recovery of palladium. The palladium concentration in solution during the reaction correlates clearly with the progress of the reaction and indicates that dissolved molecular palladium is in fact the catalytically active species. Dissolved palladium is redeposited onto the support at the end of the reaction. Additional minimization of the palladium content in solution (down to 0.1 ppm) could be achieved by simple procedures which meet the requirements of pharmaceutical industry.