Halides, aryl reaction with arylboronic acids

Under copper catalyzed conditions azoles (i.e. imidazoles) couple not only with aryl halides but also with arylboronic acids. The reaction, run in the presence of oxygen, follows a unique path (for details see Chapter 2.5.). From the synthetic point of view, the arylation of imidazole proceeds in good yield, although the regioselectivity in the arylation of 4-substituted imidazoles is only moderate (6.70.),102... 

Alkylboronic acids and arylboronic acids, RB(OH)2, and ArB(OH)2, respectively, are increasingly important in organic chemistry. The palladium catalyzed coupling reaction of aryl halides and aryl triflates with arylboronic acids (the Suzuki-Miyaura... 

Unactivated aryl iodides undergo the conversion Arl — ArCHj when treated with tris(diethylamino)sulfonium difluorotrimethylsilicate and a palladium catalyst.131 A number of methods, all catalyzed by palladium complexes, have been used to prepare unsymmetrical biaryls (see also 3-16). In these methods, aryl bromides or iodides are coupled with aryl Grignard reagents,152 with arylboronic acids ArB(OH)2,153 with aryltin compounds Ar-SnR3,154 and with arylmercury compounds.155 Unsymmetrical binaphthyls were synthesized by photochemically stimulated reaction of naphthyl iodides with naphthoxide ions in an SrnI reaction.156 Grignard reagents also couple with aryl halides without a palladium catalyst, by the benzyne mechanism.157 OS VI, 916 65, 108 66, 67. 

Although steric hindrance of aryl halides is not a major factor in the formation of substituted biaryls, low yields are obtained when ortho-disubstituted arylboronic acids are used. For example, the reaction with mesitylboronic acid proceeds only slowly because of steric hindrance during transmetalation to the palladium(II) complex. 

After the discovery of a cross-coupling reaction of arylboronic acids with aryl halides or triflates, numerous syntheses of natural and unnatural biaryls have been explored (Equation (204)). 

Although there is no direct evidence that the boronate anions, such as RB(OH)3, are capable of effecting the transmetafl tiQQjit is quite reasonable to assume a similar effect of the base for the transmetallation of organoboronic acids. The cross-coupling reaction of arylboronic acids with aryl halides at pH 7-8.5 is retarded relative to the reaction at pH 9.5-11 [51]. The of phenylboronic acid is 8.8, thus suggesting the formation of the hydroxyboronate anion [RB((OH)3 at pH > pA and its transmetallation to the palladium(II) halides. The formation of ArB(OH)3 at pH 11-12 has been reported [52]. 

The so-called Suzuki coupling reaction [1] is considered one of the most important synthetic tools to make unsymmetrical biaryl building blocks [2]. It comprises the coupling of aryl- or vinyl halides with arylboronic acids according to eqs. (la) and (lb). Palladium compounds are the catalysts of choice. 

The coupling reaction of arylboronic acids with aryl halides offers a direct and excellent route for the synthesis of a variety of biaryls. The same type of reaction proceeds with pyridylborane derivatives to provide an efficient alternative for the arylated pyridines as well. For example,... 

Several chemo-selective aryl-aryl coupling reactions of aromatic halides and organometallics with transition-metal catalysts are known.16 For example, coupling reactions of arylboronic acids with aryl halides with Pd(0) catalyst,17 arylmagnesium halides with aryl halides with Ni(II) catalysts,18 and aryl trialkyl tin compounds with aryl halides with Pd(0) catalyst19 are well known. The polyhalo-aromatic substances were converted into AB -type monomers by selective metallation of one of the halo-functional groups in each monomer. 

The Suzuki reaction of arylboronic acid derivatives with aryl halides is one of the most powerful methods for construction of an unsymmetrically substituted biaryl derivative [11, 23, 85]. Due to the importance of substituted biaryls as building blocks for pharmaceuticals, there is currently a great deal of interest in the coupling of economically attractive aryl halides with arylboronic acids [86-98]. 

Palladacycles prepared by the addition of furancarbothioamide to a methanol solution of Li2PdCl4 at room temperature are soluble in hexane, chloroform, and moderately soluble in polar solvents DMF and DMSO [187]. These palladacycles are thermally stable, not sensitive to air or moisture, and can be applied effectively in the Heck reaction of aryl halides with terminal olefins and in the Suzuki reaction of aryl halides with arylboronic acids. These reactions were performed under aerobic conditions, leading to turnover numbers... 

Diarylimidazoles were prepared by Suzuki cross-coupling reactions of imidazole halides with arylboronic acids <05H(65)1975>. Suzuki cross-coupling reactions of 6-bromoimidazo[l,2-a]pyridines have been developed <05H(65)2979>. Cul-catalyzed iV-arylation of imidazoles and benzimidazoles with aryl bromides was achieved in a near-homogeneous system that utilized tetraethylammonium carbonate as base, 8-hydroxyquinoline as ligand and water as cosolvent <05JOC10135>. 

The palladium-catalysed Suzuki coupling reaction of aryl halides with arylboronic acids has proved to be a general and convenient synthetic tool employed in organic chemistry to prepare biaryl compounds.[1] The discovery and development of active and efficient palladium-catalyst systems have been the focus of great interest recently. New catalytic systems based on paUadium-oxazolines, such as 2-aryl oxazolines and 2,2 -(l,3-phenylene)bisoxazoline (Figure 4.1) have been developed for the coupling reaction. These catalytic systems have the potential to overcome... 

Finally, the Suzuki-Miyaura reaction, which has become one of the most versatile and important reactions for the construction of C-C bonds, could be performed in a continuous flow process under ligand-free conditions [43]. The PASSfiow reactor is suited for the coupling of 4-iodoacetophenone and other aryl halides with arylboronic acid to yield the corresponding diaryls within 3 h without formation of homocoupling by-products (Scheme 15). After collecting... 

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