Suzuki couplings solvent free

A recent publication by the group of Barbarella has disclosed the rapid preparation of poorly soluble unsubstituted and modified a-quinque- and sexithiophenes by the extensive use of bromination/iodination steps and microwave-assisted Suzuki and Sonogashira cross-couplings (Scheme 6.16) [42]. Suzuki reactions were either carried out under solvent-free conditions on a strongly basic potassium fluoride/ alumina support for the synthesis of soluble oligothiophenes, or in solution phase for the preparation of the rather insoluble a-quinque- and sexithiophenes. In both cases, 5 mol% of [l,l -bis(diphenylphosphino)ferrocene]dichloropalladium(II)... 

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). 

Scheme 2.6 Solvent-free and ligandless Suzuki coupling on potassium fluoride impregnated alumina.

Recently, microwave-assisted Suzuki couplings under solvent-free conditions resulting in thiophene oligomers have also been reported41. 

Melucci, M., Barbarella, G. and Sotgiu, G., Solvent-free, microwave-assisted ynthesis of thiophene oligomers via Suzuki coupling, /. Org. Chem., 2002,67, 8877-8884. 

The diazonium group can be replaced by a number of groups. " Some of these are nucleophilic substitutions, with S l mechanisms (p. 432), but others are free-radical reactions and are treated in Chapter 14. The solvent in all these reactions is usually water. With other solvents it has been shown that the Sj-jl mechanism is favored by solvents of low nucleophilicity, while those of high nucleophilicity favor free-radical mechanisms. The N2 group can be replaced by CP, Br, and CN, by a nucleophilic mechanism (see OS IV, 182), but the Sandmeyer reaction is much more useful (14-20). Transition metal catalyzed reactions are known involving aryl-diazonium salts, and diazonium variants of the Heck reaction (13-10) and Suzuki coupling (13-12) were discussed previously. As mentioned on p. 866 it must be... 

Heck and Stille coupling reactions, also allowing reactions to be conducted under solvent-free conditions. The synergic effect of polymer 96 and TSIL not only reflected an increased stability during storage but also an enhanced activity during catalysis. Scheme 1.62 shows a typical Suzuki reaction occurring in an aqueous biphasic medium. 

T pe of reaction C-C bond formation Reaction condition solvent-free Keywords Suzuki coupling, boronic acid... 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [222]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [223]. A solvent-free Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as base [224]. This approach has been extended to the Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 8.89) [225]. 

New labeled stilbene derivatives, such as ris-3,5-dimethoxy-4 -[ C]methoxystilbene, as-3,4, 5-trimethoxy-3 -[ C]methoxystilbene, trans-3,5-dimethoxy-4 -[ C]methoxys-tilbene, trans-3,4, 5-trimethoxy-3 -[ CJmethoxystilbene, cis-3,5-dimethoxy-4 -[ F] fluorostilbene, and trans-3,5-dimethoxy-4 -[ F]fluorostilbene, were designed and synthesized [94]. The synthesis of ( )-tris-0-methylresveratrol and ( )-3,5-dimethox-ystilbene via the Miyaura-Suzuki coupling was described [95]. This reaction has been carried out in air without solvent/substrate purification and in the absence of additional free ligand. Figure 1.18 shows a scheme of deoxyschweinfurthin synthesis accomplished in Ref [96]. 

The cross-coupling of boron compounds with aryl or alkenyl halides (Suzuki coupling) was used for the preparation of polycyclic aromatic compounds in a biphasic reaction medium. For example, 2-bromobenzonitrile and 4-methylphenylboronic acid gave 4-methyl-2"-cyanobiphenyl in good jdeld with Pd/TPPTS catalyst at 80°C in a toluene-ethanol-aqueous Na2C03 solvent mixture (Scheme 37). The product, isolated by phase separation, was free of metal or ligand impurities and the catalyst could be recycled in the aqueous phase (208). 

A facile surfactant-mediated Heck and Suzuki coupling procedure in water has been developed nsing ligand-free Pd catalysts. The procedure which involves nanometric palladinm colloids is operationally simple, environmentally benign, and synthetically as efficient as conventional procednres using organic solvents [21]. 

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