Suzuki coupling procedure

Using Kishi s modification of the Suzuki coupling procedure,45 Nicolaou et al. accomplished the convergent union of compounds 112 and 113 (see Scheme 28).38b 46 This coupling is the key step in a synthesis of (55,6/ )-dihydroxyeicosatetraenoic acid [(55,6/ )-diHETE] methyl ester (115). Importantly, the configurations of the two coupling partners are reflected in the Suzuki coupling product 114. 

Retrosynthetic Analysis. Propose syntheses of the following compounds using a Suzuki coupling procedure as a key step. Show (1) your retrosynthetic analysis and (2) all reagents and reaction conditions required to transform commercially available starting materials into the target molecules. 

The utility of this process was further demonstrated when the one-pot Suzuki coupling procedure was demonstrated to produce 188 in excellent yield [96]. Procedurally, after the first coupling had occurred, phenyl boronic acid was added along with additional Pd(PPh3)4. 

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]. 

General procedure for Suzuki coupling. 4-Bromoanisole (125 pL, 1 mmol), phenylboronic acid (186 mg, 1.5 mmol), K2CO3 (0.55 g, 4 mmol) and the BaCei.j,Pdj,03.j, catalyst were mixed in a 20 ruL scintillation vial. A preheated 2-propanol/water solution (IPA/H2O, 1 1 v/v, 12 ruL, 80°C) was added, the vial was immediately placed on a hot plate stirrer and its temperature was maintained at (80 1) °C. The reaction mixture was stirred at 1000 rpm for 3 min, then cooled to room temperature. The 4-methoxybiphenyl product was extracted with diethyl ether (3 x 15 ruL). The organic fractions were washed with deionized water and dried with MgS04. After filtration, volatiles were removed under reduced pressure to yield the isolated product. 

General procedure for Suzuki coupling reaction. A 100 mL of round-... 

General microwave assisted Suzuki-Miyaura cross-coupling procedure... 

In closely related work, similar solid-phase chemistry was employed by the same research group to prepare biaryl urea compound libraries by microwave-assisted Suzuki couplings followed by cleavage from the resin with amines (Scheme 7.47) [18]. The above described procedure enabled the generation of large biaryl urea compound libraries employing a simple domestic microwave oven. 

In a more recent study, Wang and coworkers have discussed microwave-assisted Suzuki couplings employing a reusable polymer-supported palladium complex [141]. The supported catalyst was prepared from commercial Merrifield polystyrene resin under ultrasound Bonification. In a typical procedure for biaryl synthesis, 1 mmol of the requisite aryl bromide together with 1.1 equivalents of the phenyl-boronic acid, 2.5 equivalents of potassium carbonate, and 10 mg of the polystyrene-... 

Several microwave-assisted procedures have been described for soluble polymer-supported syntheses. Polyethylene glycol) (PEG)-supported aryl bromides have been shown to undergo rapid palladium(0)-catalyzed Suzuki couplings with aryl boronic acids in water (Scheme 12.16) [63], The reaction proceeded without organic cosolvent... 

The procedure described here incorporates a number of modifications to the Suzuki coupling that result in a sound, efficient and scaleable means of synthesizing biaryls. First, the catalytic use of palladium acetate and triphenylphosphine to generate palladium(O) eliminates the need for the expensive air and light sensitive tetrakis(triphenylphosphine)palladium(0). No purification of reagents is necessary, no special apparatus is required, and rigorous exclusion of air from the reaction mixture is not necessary. Furthermore, homo-coupled products are not present in significant levels (as determined by 500 MHz 1H NMR). 

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). 

In a related study, the Shibasaki group examined cyclizadon of naphthyl triflate 10.1 (Scheme 8G.10) [23], Cyclization of 10.1 under standard cationic conditions gave Heck product 10.2 in 78% yield and 87% ee. Evidently, the reaction is fairly tolerant of the nature of the aryl group, because both 10.1 and 9.3 behaved similarly. An interesting variation of this reaction was also demonstrated in which Suzuki coupling and asymmetric Heck cyclization were performed in a one-pot operation. Thus, treatment of ditriflate 10.3 with borane 10.4 under standard Heck conditions provided 10.2 in similar enantioselectivity to the stepwise procedure, albeit in quite low yield. Heck product 10.2 was converted in several steps to the natural products, halenaqui-none (10.5) and halenaquinol (10.6). 

General Procedure for Cleavage of Phenols Using the Suzuki Coupling Reaction Preparation of Resins 15-17 and Compounds 18... 

An improved procedure of Suzuki-couplings was recently described by Buchwald [5] et al. By using 0-(di-tert.butyl-phosphino)-biphenyl as ligand, palladium acetate and potassium carbonate couplings are facilitated at room temperature [eq. (c)]. 

In 1996, workers at GlaxoWellcome disclosed the solution-phase preparation of 2-aminothiazole combinatorial libraries [99], Utilizing 20 glass vials and a DPC liquid dispensing robot, they prepared a library of 2500 compounds by this procedure. Also in 1996, Argonaut reported the use of their computer-controlled fluid delivery system for biaryl synthesis via a Suzuki coupling reaction [61],... 

Another total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B has been developed by Hoye et al. [32], who emphasized that Suzuki coupling of the boronic acid derived from the naphthalene moiety with a THIQ-iodide proved to be the most generally effective method for forming the hindered biaryl bond. A racemic isochromane analogue of michellamines has been synthesized by a similar procedure [33]. 

Cypridina luciferin is an imidazopyrazinone involved in the bioluminescence of the crustacean Cypridina (Vargula) hilgendotfii. The first total synthesis of this natural product was achieved by Kishi in 1966, which was followed by that of White and Karpetsky in 1971. Most recently, Nakamura et al. developed a convenient, direct procedure for this synthesis, employing Suzuki coupling (Eq. (36)) [67]. 

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