THE SUZUKI COUPLING REACTION

The Suzuki coupling reaction, also called the Suzuki-Miyaura reaction, couples an aryl, or vinyl halide to an aryl or vinyl boronic acid in which the Suzuki catalyst—a palladium catalyst with four triphenylphosphine ligands—plays the central bond forming role. 

The palladium, Pd(0), atom of the catalyst is at the center of a tetrahedron. A triphenylphosphine group (PPh3) is at each corner of the tetrahedron. 

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Of particular synthetic importance is the coupling of aryl- and hetarylboronic acids to aryl- and hetaryl halides (or triflates), allowing for a convenient synthesis of biphenyls, even sterically demanding derivatives such as 14, hetaryl phenyls and Zj/ -hetaryls. With appropriately disubstituted aromatic substrates, the Suzuki coupling reaction can be applied in the synthesis of polyphenylene materials. 

The biaiyl phenol (X) was the penultimate intermediate in the synthesis of this final drag substance. Thus after the Suzuki coupling reaction is performed to give the phenol, the levels of Pd have to be lowered to < 10 ppm. In the pharma industry this can be a significant problem. Additionally there is always batch to batch variability observed when catalysts like Pd2(dba)3 have been used in Suzuki couphng reactions. 

Polymer 163 (and similar alternating copolymers of 9,9-dioctylfluorene and oxadiazole <2002MM3474>) with blue-light-emitting activity were synthesized by the Suzuki coupling reaction and studied by GPC, MALDI-TOF MS, LJV spectroscopy, and several other techniques <2002ANC6252>. 

As we have seen in Chapter 1, the Suzuki coupling reaction is a powerful method for preparing biaryls and several applications in pyrrole chemistry have been described. Schliiter reported the first pyrrole boronic acid 57, but, surprisingly, the related pyrrole borate 58 could not be hydrolyzed [15]. 

S. Guillerez and G. Bidan, New convenient synthesis of highly regioregular poly(3-octylthiophene) based on the Suzuki coupling reaction, Synth. Met., 93 123-126, 1998. 

The palladium nanoparticle is prepared from the reaction of the stabilizer, 4,4 -bis(perfluorooctyl)dibenzylideneacetone with palladium(II) chloride. The average size of the nanoparticle varied according the ratio of PdCF to the stabilizer, but was typically around 4 or 5 nm. The initial yield observed in the Suzuki coupling reaction was 90%, but decreased to 78% after five consecutive runs. Fluorous boronates (alternative precursors in Suzuki reactions), have also been developed for use in fluorous biphasic processes [12], A generic structure of a fluorous boronate is shown in Figure 10.2. 

Palladium catalysts have been found which are effective in the Suzuki coupling reaction of arylboronic acids with aryl chlorides carrying electron-withdrawing groups.73 Biaryls may also be synthesized by cross-coupling of arylboronic acids with arenediazonium salts.74,75 There has been a report of the polymer-bound palladium-catalysed Suzuki coupling of aryl triflates with organoboron compounds.76 Arylbor-onates may themselves be synthesized by the palladium-catalysed reactions of... 

Cleavage of the Resin-Bound Phenols Using the Suzuki Coupling Reaction... 

The Suzuki coupling reaction is a powerful tool for carbon-carbon bond formation in combinatorial library production.23 Many different reaction conditions and catalyst systems have been reported for the cross-coupling of aryl triflates and aromatic halides with boronic acids in solution. After some experimentation, we found that the Suzuki cleavage of the resin-bound perfluoroalkylsulfonates proceeded smoothly by using [l,l -bis (diphenylphosphino)ferrocene]dichloropalladium(II), triethylamine, and boronic acids in dimethylformamide at 80° within 8 h afforded the desired biaryl compounds in good yields.24 The desired products are easily isolated by a simple two-phase extraction process and purified by preparative TLC to give the biaryl compounds in high purity, as determined by HPLC, GC-MS, and LC-MS analysis. 

The Suzuki coupling reaction of 2-haloselenophenes with boronic acids catalyzed by palladium salt is a new route to prepare 2-arylselenophenes and 2,5-diarylselenophenes in good yields. In addition, 2-arylselenophenyl ketones were also obtained by this protocol from 2-iodoselenophene and boronic acids via a carbonylative process [130],... 

Ladlow and coworkers recently developed an acid-labile fluorous benz-aldehyde protecting group 43 to facilitate the parallel synthesis of sulfonamides 44 (Scheme 25) [56]. The Suzuki coupling reaction was conducted under microwave irradiation. All the intermediates and the final products were purified by F-SPE. 

The microreactor plant will be equipped with the process control and online analysis [47]. The Suzuki coupling reaction is investigated as a common synthetic route for polymeric semiconductors. The transfer of the developed microflow process into chemical production is accompanied by economic and ecologic evaluations. 

Molander GA, Ellis N (2007) Organotrifluoroborates protected boronic acids that expand the versatility of the Suzuki coupling reaction. Acc Chem Res 40 275-286... 

A modification of the Suzuki coupling reaction proved to be a clean and useful method for the preparation of monosubstituted arylferrocenes. Iodoferrocene was reacted with a series of substituted arylboronic acids in the presence of sodium carbonate and palladium acetate in aqueous ethanol at room temperature to produce a range of substituted monoarylfer-rocenes (Eq. (19)). A systematic investigation undertaken to determine the optimal reaction conditions indicated that scrupulous deoxygenation of the solvent is critical. The use of... 

Zhang and Allen [97] have recently reported an easily prepared, air- and moisture-stable resin-bound palladium catalyst for the Suzuki coupling reaction. Commercially available resin-bound thiourea, Deloxan THP II [98], was used as the starting material. The resin-bound catalyst was prepared simply by treating the wet Deloxan resin with a solution of Pd(OAc)2 in methanol. Suzuki coupling reactions were then carried out using the resin at a... 

In the course of a study of structure-based design and synthesis of a potent matrix metallo-proteinase-13 inhibitor based on a pyrrolidinone scaffold, the Suzuki coupling reaction of a,/ -unsaturated /-lactam iodide (40) with 4-methoxyphenylboronic acid was carried out to give the corresponding coupling product in 77 % yield (Eq. (76)) [119]. 

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>. 

Narayanan R, El-Sayed MA (2004) Effect of colloidal catalysis on the nanoparticle size distribution dendiimer-Pd vs PVP-Pd nanoparticles catalyzing the Suzuki coupling reaction. J Phys Chem B 108 8572... 

The Suzuki coupling reaction is a powerful tool for the construction of biaryl compounds and their homologues, which are key structural elements of various natural products, polymers, and compounds of medicinal interest. Aryl boronic acids and their esters are the usual substrates in reactions with aryl or heteroaromatic halides and... 

As was shown earlier with the Suzuki coupling reactions, organopalladium intermediates can show good stability to water and other protic sources. This stability has been exploited in the synthesis of polyacetylene under air- and moisture-stable conditions. It was found that simple palladium(II) salts (PdCl2, Pd(CH3C02)2, etc.) can be used to initiate the 1,2-insertion polymerization of strained cyclic alkenes in water (eq. (8)) [31]. Once formed, poly-8 can be converted to polyacetylene through a retro-Diels-Alder reaction. 

A polyarylene, 123, containing a chiral binaphthyl group has been synthesized via the Suzuki coupling reaction.207 The polymer may have a helical structure segmented by a phenylene group. Another optically active polyarylene has been synthesized and its conformation has been considered.208... 

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