Boronic acids palladium-catalyzed cross-coupling

The Suzuki reaction (the palladium-catalyzed cross-coupling of aryl halides with boronic acids) is arguably one of the most versatile and at the same time also one of the most often used cross-coupling reactions in modern organic synthesis [32], Carrying out high-speed Suzuki reactions under controlled microwave conditions can today be considered almost a routine synthetic procedure, given the enormous literature precedent for this transformation [7]. 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

Phosphoric acids 3 bearing different aromatic substituents at the 3,3 -positions can be synthesized in a few steps starting from commercially available BINOL (6) (Scheme 3). The key step involves a palladium-catalyzed cross-coupling of boronic acid 7 and the respective aryl halide. Both the electronic and steric properties of potential catalyst 3 can be tuned by a proper choice of the substituents at the 3,3 -positions. Besides a simple phenyl group, Akiyama et al. introduced monosubsti-tuted phenyl derivatives as well as a mesityl group, whereas Terada and coworkers focused on substituents such as biphenyl or 4-(2-naphthyl)-phenyl. 

Chloro-P-carboline (25) has served as a common intermediate in palladium-catalyzed cross-coupling reactions, offering easy access to several pyridine alkaloids. In Bracher s total synthesis of perlolyrine (27), a P-carboline alkaloid, the Suzuki reaction of 25 with 5-formylfuranyl-2-boronic acid (26) formed the C-C bond between the pyridine and the furan rings <92LA1315>. Reduction of the resulting Suzuki adduct with NaBIL subsequently... 

Li and Yue also reported the intermolecular palladium catalyzed cross coupling reactions of bromo quinoxalines 214 and 216 with aryl boronic acids and heterocyclic stannanes, respectively <99TL4507>. The Suzuki couplings (i.e., 214 215) required the use of a... 

The benzene derivatives containing the fluorinated sulfone have been prepared either by nucleophilic substitution of the 4-fluorophenyl derivative (e.g. 1) or by starting with the appropriately substituted sodium thiophenoxide and reacting with perfluoroalkyl iodide follow by oxidation with either MCPBA or chromium oxide (12. li.) The biphenyl derivatives have been prepared by palladium catalyzed cross coupling chemistry of the 4-bromophenyl derivative (e.g. 2) with substituted phenyl boronic acid (yields 37-84%) (JLH, .). Compound 16 has been prepared by palladium catalyzed cross coupling of (4-bromophenyl)perfluorohexyl sulfone with vinyl anisole in 37 % yield (JJL). The vinyl sulfones, 7 and 9, have been prepared by condensation of CH3S02Rf (JJL) with the appropriate aldehyde (yields 70,and 73%) following a literature procedure (1 ). Yields were not optimized. 

Suzuki couphng, the palladium-catalyzed cross-coupling of aryl or vinyl hahdes with organoboronates, is employed widely in organic synthesis. The reaction is most often carried out in an organic solvent (benzene) in the presence of a base [228]. Because of the reasonable stabihty of boronic acids and esters towards hydrolysis, Suzuki couphng can also be carried out in aqueous media. An extensive study of the reaction has shown that similar results are obtained in aqueous and non-aqueous systems [229]. 

Imidazoles and fused-derivatives have participated in a myriad of cross-coupling reactions. 2-Thiomethylrmidazolm-5-one 102 underwent efficient palladium-catalyzed cross-coupling reactions with boronic acids in the presence of copper(l)thiophene-2-carboxylate (CuTC) to give... 

The procedure is very easy to reproduce and the palladium-catalysed crosscouplings may be applied to a wide range of substituted 4-tosylcoumarin and arylboronic acids. The method successfully broadens existing approaches for the cross-couplings of tosylate with boronic acids by using palladium as the catalyst. Table 4.1 demonstrates diverse tosylates that can undergo palladium-catalyzed cross-couplings with various arylboronic acids successfully. 

The coupling of stable organosulfur compounds with boronic acids is of great synthetic importance, since both reaction partners are readily available, low toxicity, and are stable toward many reagents. 4-Halo-n-butyl and normal thio esters (Fig. 2) were prepared and investigated as substrates for palladium-catalyzed cross-coupling with boronic acids. 

Palladium catalyzed cross coupling between 4-iodo substituted pyridines, (55) and (56), and aryl boronic acids, (57) and (58), has been used in syntheses of 1,7-naphthyridine (94JHC(31)11) and P-carboline (Scheme 25) (94TL(35)2003>. 

Suzuki-Miyaura reactions are perhaps the most widely employed palladium catalyzed cross-couplings in the realm of thiazole medicinal chemistry. They typically take place only when the thiazole is an electrophile in the transformation. The nucleophilic thiazole boronic acid or ester, especially at the 2-position, is relatively unstable and therefore difficult to prepare. The electrophiles namely the 2-, 4-, or 5-substituted halothiazoles are often readily accessible in terms of their synthetic ease or commercial availability. A remarkable application has been described by Jang et al. in the discovery... 

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