Palladium-promoted reactions Suzuki

At the opposite of the molecular chemistry described until now, nanoparticles are reminiscent of heterogeneous catalysts. However, these colloid-derived materials have been shown to catalyze efficiently in water coupling reactions which have been previously described in pure homogeneous systems. For instance, poly(N-vi-nyl-2-pyrrolidine)-stabilized palladium nanopartides promote the Suzuki crosscoupling in aqueous media with high yields (see also Section 6.6) [87]. 

Application of immobilized palladium catalyst under the action of MW, with phase-transfer agents, has also been reported to promote the Suzuki reactions of a range of aryl halides and triflates in solvents such as water and ethanol under MW conditions [120, 121]. Similar results were obtained when aryl halides were attached to a PEG matrix as para-substituted benzoates [122]. It was found that conventional thermal conditions induced up to 45% cleavage of the benzoates whereas this side reaction was suppressed when MW conditions were employed. 

Another topic often encountered in the literature on microwave-promoted reactions is the lower consumption of energy associated with the use of MW technology in small-scale chemistry. For the palladium-catalyzed Suzuki reaction there have been attempts to investigate this matter in more detail. Clark et al. have performed a comparative study of the energy efficiency of the different reaction techniques. The Suzuki reaction was analyzed and under the reaction conditions used the MW-assisted reaction was 85 times more energy-efficient than the corresponding oil-bath-heated reaction. As there are a multitude of reaction conditions for the Suzuki coupling, this value should be seen as an example, rather than a definite value [20]. 

A more sophisticated procedure has recently allowed the preparation of palladium complex 34, based on an intramolecular Suzuki coupling. The key intermediate 39 is generated by oxidative addition of palladium(O) to 38, and treatment of 39 with base promotes a Suzuki-type intramolecular reaction leading to 34 (Scheme 7) [26]. The same procedure is applicable to the synthesis of benzyne-nickel complexes with a variety of ligands (PPh3, PCy3, PEt3) [26]. 

Due to their widespread application in the Suzuki-Miyaura reaction, arylboronic acids are attractive aryl transfer precursors. However, in the zinc-promoted reaction, an excess of Et2Zn (up to 7equiv.) must be added in order for efficient transmetallation to occur. The application of a reactive aryl metal species necessitating only a catalytic amount of metal would thus be advantageous. In recent years, several rhodium-catalyzed enantioselective protocols have been described, as well as processes involving palladium and nickel. 

Bromo- and iodoimidazoles are useful intermediates for further functionalization. 4(5)-Aryl- I //-imidazoles 57 can be efficiently and selectively prepared by palladium-catalyzed Suzuki-Miyaura reaction of commercially available 4(5)-bromo-l//-imidazole 56 with arylboronic acids under phase-transfer conditions, which then underwent highly selective palladium-catalyzed and copper(I) iodide mediated direct C-2-arylation with a variety of aryl bromides and iodides under base-free and ligandless conditions to produce 2,4(5)-diaryl-l//-imidazoles 58 in modest to good yields <07JOC8543>. A new procedure for the synthesis of a series of substituted 2-phenylhistamines 60 utilizing a microwave-promoted Suzuki... 

Phenylazo-1,2,4-triazole were prepared from benzenediazonium chloride and 1,2,4-triazole <07SC1977>. 5-Aryltriazole acyclonucleosides 134 with various aromatic groups on the triazole ring were synthesized from precursor 133 via the Suzuki coupling reaction in aqueous solution and promoted by microwave irradiation <07TL2389>. 1-Methyl-1,2,4-triazole 135 participated in a palladium-catalyzed C-H arylation reaction with 3,5-dimethoxychlorobenzene 136 to give coupled product 137 <07OL1449>. 

Erdelyi, M., Gogoll, A. Rapid Microwave Promoted Sonogashira Coupling Reactions on Solid Phase. J. Org. Chem. 2003, 68, 6431-6434. Najera, C., Gil-Molto, J., Karlstroem, S., Falvello, L. R. Di-2-pyridylmethylamine-Based Palladium Complexes as New Catalysts for Heck, Suzuki, and Sonogashira Reactions in Organic and Aqueous Solvents. Org. Lett. 2003, 5,1451-1454. 

However, efforts were also directed to the development of phosphine-free catalysts. For example, the ligand-free Pd(OAc)2 promoted Suzuki reaction in water was reported using microwave heating. In this way, a low palladium loading (0.4 mol.%) was required and the cross coupling proceeded quickly (5-10 min reaction time), using boronic acids and aryl iodides, bromides and chlorides. 

Under the reaction conditions, phenylacetylene was found to be a much more reactive coupling partner than arylboronic acids in the analogous Suzuki-Miyaura coupling, as in addition to the desired product (38), alkynylation and further addition reactions occurred with a variety of transient palladium(II) species (Scheme 27). Despite these undesired side reactions, Catellani was able to fine-tune the reaction conditions to form predominantly product 38 or 39. The formation of the desired product 38 (and suppression of product 39) is promoted by acceleration of norbomene carbopalladation by KOAc [47] and by using an excess of alkyl halide affording several structurally similar unsymmetrical alkyne products in good yields (Scheme 28). 

Couplings. Both bis(imidazolylidene) and mixed imidazolylidene-phsophine complexes of palladium (1,2) are good catalysts for promoting Suzuki and Stille coupling reactions. 

The reaction is not restricted to forming biaryls. Aryl boronic acids can also react with vinyl halides and vinyl triflates in the presence of palladium (0). Thallium (I) ethoxide is known to promote Suzuki cross coupling reactions for vinyl or arylboronic acids with vinyl and aryl halide partners. 3 synthetic example is... 

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