Biaryl by-products

Fenton s reagent hydroxylates aromatic rings, generally with low yields, at the more nucleophilic carbon positions, and gives substantial amounts of biaryl by-products resulting from the dimerization of intermediate radical species (equation 217).491... 

The total synthesis of the proteasome inhibitor cyclic peptide TMC-95A was accomplished by. S.J. Danishefsky and co-workers. The biaryl linkage in the natural product was constructed by a Suzuki cross-coupling between an aryl iodide and an arylboronic ester derived from L-tyrosine. The required arylboronic pinacolate substrate was prepared using the Miyaura boration. The aryl iodide was exposed to b/s(pinacolato)diboron in the presence of a palladium catalyst and potassium acetate in DMSO. The coupling proceeded in high yield and no symmetrical biaryl by-product was observed. 

A novel macrocyclization reaction was developed based on a domino Miyaura boration intramolecular Suzuki crosscoupling sequence in the laboratory of J. Zhu. " This strategy was applied in the synthesis of biaryl-containing macrocycles. The diiodide substrate was dissolved in degassed DMSO, and then the catalyst and the base were added. Successful macrocyclization required extensive experimentation, and the authors determined that the concentration and the nature of the base were the two most important factors. Interestingly, potassium carbonate is not suitable as a base in the Miyaura boration, since it tends to give biaryl by-products, but in this particular macrocyclization reaction it proved to be completely ineffective because the reaction failed to take place. 

The Pd-catalyzed cross-coupling reaction of the pinacol ester of diboronic acid with aryl halides and triflates gives a direct procedure for various functionalized arylboronic esters (Table 6), which are useful for highly efficient and selective carbon-carbon bond formation by Pd catalysts (Sect. III.2.2). The combination of PdCl2(dppf) with KOAc (and dppf) is effective in the carbon-boron bond formation. KOAc is essential not only to accelerate the reaction but also to prevent the formation of biaryl by-products. 

In 1993 Suzuki and colleagues described the palladium-catalyzed carbonylative coupling of aryl iodides with aryl boronic acids [13]. Various diarylketones were produced in high yields (Scheme 4.4). The choice of base and solvent was essential to obtain the desired ketones without biaryl by-products. The coupling of benzyl bromide was also described. In 1998 the group extended this methodology to aryl bromides and triflates [14]. In the case of aryl bromides, Nal or KI was required as an additive. The in situ transformation of aryl bromides to aryl iodides may be involved. 

An alternative reaction mechanism has been suggested for nitroarylation of enolates. An impetus for considering other mechanisms is the fact that the by-products which might be expected from aryl radicals, such as reduction products from hydrogen abstraction from the solvent or biaryls from coupling, are not observed. One alternative is that, rather than being a chain process, the reaction may involve recombination whereby the radicals combine more rapidly than they separate. 

Several products other than 2,2 -biaryls have been isolated following reaction of pyridines with metal catalysts. From the reaction of a-picoline with nickel-alumina, Willink and Wibaut isolated three dimethylbipyridines in addition to the 6,6 -dimethyl-2,2 -bipyridine but their structures have not been elucidated. From the reaction of quinaldine with palladium-on-carbon, Rapoport and his co-workers " obtained a by-product which they regarded as l,2-di(2-quinolyl)-ethane. From the reactions of pyridines and quinolines with degassed Raney nickel several different types of by-product have been identified. The structures and modes of formation of these compounds are of interest as they lead to a better insight into the processes occurring when pyridines interact with metal catalysts. 

Biaryl ethers are a well-known motif in medicinal chemistry. The reaction of p-nitrophenol with 2,4-dichloropyrimidine was performed in a mixture of acetone and water from which the product precipitated after completion. Work-up and isolation of the product was therefore very simple. We also observed the formation of a by-product (depend-... 

The reactions are performed treating diarylteUurium dichlorides or aryltellurium trichlorides with excess olefin (5-10 mol equiv) in the presence of Pd(II) chloride-sodium acetate in refluxing acetic acid or acetonitrile. The yields are moderate to good with the dichlorides and poor with the trichlorides. Minor amounts of biaryls are the usual by-products beyond acetoxylated arylalkenes (formed by the addition of acetic acid to the olefins). 

Tllmann Reaction. Although the -Ullmann reaction is considered usually, in connection with the preparation of symmetrical biaryls, it has been employed also to prepare unsymmetrical biaryls. Thus, o-terphenyl has been synthesized by heating a mixture of iodobenzene and 2-iodobiphenyl with copper 44 biphenyl and 2,2 -diphenylbiphenyl were by-products of the reaction. 

When it is difficult to remove traces of azo compounds from the biaryl by distillation or recrystallization, chemical means may be employed. Colorless 4-bromobiphenyl was obtained by treating an alcoholic solution of the yellow product with a little zinc dust and hydrochloric acid.60 In the preparation of 3-bromobiphenyl, the crude reaction mixture was shaken with portions of concentrated sulfuric acid until the red color of the solution was removed.61... 

A new synthetic approach to fluorescent 4-amino-4 -boryl biaryls by a boronate selective Suzuki-coupling of / -(dimesitylboryl)phenylboronates with haloarenes under the employed reaction conditions has been reported. The triarylboryl unity is not attacked whereas non-sterically hindered triarylboranes like tri-l-naphthylborane gave coupling products in good yields 207.120... 

Treatment of diaryl tellurium dichlorides, obtainable from tellurium tetrachloride and aromatic compounds, with carbon monoxide in the presence of palladium(II) chloride/lithium chloride gives arenecarboxylic acids. Biaryls are formed as by-products . Similar products were obtained when the diaryl tellurium dichlorides were reacted with nickel tetracarbonyF. 

Biaryl formation using Stille coupling suffers from the problem of by-product formation, which is apparently due to ligand exchange between palladium and phosphorus subsequent to oxidative addition of the aryl halide to palladium (Scheme 4-35). A detailed paper dealing with this phenomenon has appeared [128]. In unfavorable cases the required biaryl can be the minor product. 

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