Suzuki catalyst recycle

Palladium-catalyzed Suzuki cross-coupling reactions can be conducted in the ambient temperature ionic liquid, l-butyl-3-methylimidazolium tetrafluoroborate (29), in which unprecedented reactivities are witnessed, and which allows easy product isolation and catalyst recycling (Eq. (60)) [96]. 

Nitrile-functionalized ILs have been used in Stille, Suzuki and Heck reactions and their usefulness became apparent upon catalyst recycling while in conventional ILs the activity rapidly decreased to zero, in nitrile-functionalized... 

Catalyst Recycling in Batch and Semi-Continuous, Fixed-Bed Processes for Suzuki Cross-Coupling Reactions... 

Although a recent report by Hirao and co-workers presents Pd/C as a reusable catalyst for Suzuki coupling of iodophenols in aqueous media, studies that examine reuse of Pd/C for coupling of aryl bromides have not been reported. In this paper we describe both a batch Suzuki cross-coupling reaction with catalyst recycling and a semi-continuous fixed bed system for Suzuki coupling of aryl bromides. 

Due to the growing importance of asymmetrically substituted biaryl derivates used as drug intermediates, the Suzuki coupling reaction is increasingly important. Mostly, however, large amoimts of catalyst are used and the catalyst recycling is often hindered by precipitation of palladium black. 

Catalyst recycling can be affected by adding a fresh heptane solution of the reactants (plus a new portion of phenylboronic acid to the DMA layer for the Suzuki reactions), reseaUng the system, and heating to 95°C. 

An early example of Suzuki-Miyaura coupling smdied at an industrial laboratory is shown by reaction 7.4.2.3. The product 2-cyano-4 -methylbiphenyl is a building block for a class of antihypertensive pharmaceuticals. The use of triphenyl phosphine trisulfonated (TPPTS) as the ligand allows the formation of a biphasic system and easy catalyst recycle. 

Scheme 6.28 Catalyst recycle in Suzuki coupling in water.

Table 27.3. Effect of recycling the BaCeo 95Pdo o503. catalyst, on yields in Suzuki coupling ...

Shylesh, S., Wang, L. and Thiel, W.R. (2010) Palladium(II)-phosphine complexes supported on magnetic nanoparticles filtration-free, recyclable catalysts for Suzuki-Miyaura crosscoupling reactions. Advanced Synthesis and Catalysis, 352 (2-3), 425-432. 

Stevens, P.D., Li, G.F., Fan, J.D., Yen, M. and Gao, Y. (2005) Recycling of homogeneous Pd catalysts using superparamagnetic nanoparticles as novel soluble supports for Suzuki, Heck, and Sonogashira cross-coupling reactions. Chemical Communications (35), 4435-4437. 

Apart from examples involving Suzuki reactions with standard soluble palladium catalysts, there is a growing number of publications reporting the use of immobilized, recyclable palladium catalysts for carrying out Suzuki and other cross-cou-... 

The group of Ley has reported on the use of palladium-doped perovskites as recyclable and reusable catalysts for Suzuki couplings [151]. Microwave-mediated cross-couplings of phenylboronic acid with aryl halides were achieved within 1 h by utilizing the supported catalyst (0.25 mol% palladium) in aqueous 2-propanol (Scheme 7.127). The addition of water was crucial as attempted transformations in non-aqueous mixtures did not proceed. 

Greater durability of the colloidal Pd/C catalysts was also observed in this case. The catalytic activity was found to have declined much less than a conventionally manufactured Pd/C catalyst after recycling both catalysts 25 times under similar conditions. Obviously, the lipophilic (Oct)4NCl surfactant layer prevents the colloid particles from coagulating and being poisoned in the alkaline aqueous reaction medium. Shape-selective hydrocarbon oxidation catalysts have been described, where active Pt colloid particles are present exclusively in the pores of ultramicroscopic tungsten heteropoly compounds [162], Phosphine-free Suzuki and Heck reactions involving iodo-, bromo-or activated chloroatoms were performed catalytically with ammonium salt- or poly(vinylpyrroli-done)-stabilized palladium or palladium nickel colloids (Equation 3.9) [162, 163],... 

Kim, S.W. et al., Fabrication of hollow palladium spheres and their successful application to the recyclable heterogeneous catalyst for Suzuki coupling reactions, J. Am. Chem. Soc., 124, 7642, 2002. 

Buchwald has shown that, in combination with palladium(II) acetate or Pd2(dba)3 [tris(dibenzylideneacetone)dipalladium], the Merrifield resin-bound electron-rich dialkylphosphinobiphenyl ligand (45) (Scheme 4.29) forms the active polymer-supported catalysts for amination and Suzuki reactions [121]. Inactivated aryl iodides, bromides, or even chlorides can be employed as substrates in these reactions. The catalyst derived from ligand (45) and a palladium source can be recycled for both amination and Suzuki reactions without addition of palladium. 

Corma et al compared the use of different IL solvents and polyethylene glycol (PEG) using a carbopalladacycle complex as catalyst for Suzuki and Sonogashira reactions. They showed that the dialkyl-substituted imidazolium compounds had poor stability, reactivity and recyclability when compared with trialkyl substituted imidazolium compounds and PEG. They concluded that this result could be attributed to the stabilization of the Pd nanoparticles in the solvent. They showed that PEG was a better solvent since it gave better yields, had good stability, low cost and low toxicity. 

A similar reaction was reported by Kabalka et al. where ligandless and solvent-free Suzuki couplings were performed with potassium fluoride on alumina. This reaction is very interesting as the catalyst used was palladium powder, the least expensive form of palladium available32. The authors demonstrated the simplicity of the procedure by efficient isolation of the biaryl products via a simple filtration. This could be done as the palladium catalyst remains adsorbed on the alumina surface. A small amount of water in the matrix was beneficial for the outcome of the reactions. Recycling of the catalyst was possible by adding fresh potassium fluoride to the palladium/alumina surface and the catalytic system remained effective at least through six reaction cycles (Scheme 2.6). 

The use of solid supported, recyclable catalysts, is a well-assessed technique in classic organic chemistry, and many exhaustive reviews dealing with this subject are available [105, 115]. The use of solid supported catalysts for library synthesis in solution has also been reported. Among others, Kobayashi et al. presented the use of a new supported scandium catalyst for 3CC reactions leading to solution libraries of amino ketones, esters, and nitriles (24-member model discrete library) [116], or to quinolines (15-member model discrete library) [117], and Jang [118] presented a polymer bound Pd-catalyzed Suzuki coupling of organoboron compounds with halides and triflates. This area was also briefly reviewed recently [119]. 

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