Dimer biaryls

Previously Davidson and Triggs have reported that arylboronic acids react with sodium palladate to give the dimeric biaryls. The synthetic utility of this dimerization reaction is, however, limited owing to stoichiometric requirement of the palladium compound. On the other hand, the palladium-catalyzed crosscoupling reaction between arylboronic acids and haloarenes in the presence of bases provides a clean synthesis of biaryls (Eq. 106) In this case, sodium carbonate has been proven to be most effective base. 

The very minor amounts of dimer biaryls which were formed in this discharge suggested that radical intermediates were not of dominant importance. The lack of formation of the xylene isomers was also interpreted as supporting the absence of methyl radicals in the plasma. 

The formation of substantial amounts of dimer biaryls bibenzyl, diphenylmethane and biphenyl is of particular significance since, as noted above, the formation of only trace amounts of these dimer biaryls was observed in the microwave discharge. Additional experiments were conducted in which a helium carrier gas was used, and no substantial difference in the nature and amounts of products formed was noted. The change in product ratios, therefore, appears to reflect a change in mechanism which results from the use of an RF. powered discharge. 

Functional biaryl derivatives are important industrial chemicals. They are used as monomers for the production of high performance and other polymers, as well as dyes, pharmaceuticals and agrochemical intermediates. We have developed an improved method for the dehalogeno-dimerization of aryl bromides to yield biaryl derivatives under mild conditions (temperature < 100°C, atmospheric pressure) using a common base, a 5 % Pd/C catalyst (0.1 - 10 % w/w, based on the starting material) in an aqueous medium and formyl hydrazine as the reducing agent. Several examples of biaryl derivatives are discussed. 

In the presence of a precious metal catalyst, aryl halides can undergo dehalo-dimerization to give biaryl products, with varying degrees of selectivity. The major byproduct of this reaction is usually the dehalogenated aryl compound. This type of chemistry is currently one of the very few viable means for the large scale preparation of biaryl compounds. 

In another nonelectrolytic process, arylacetic acids are converted to vi c-diaryl compounds 2A1CR2COOH —> ArCR2CR2Ar by treatment with sodium persulfate (Na2S20g) and a catalytic amount of AgNOs." Both of these reactions involve dimerization of free radicals. In still another process, electron-deficient aromatic acyl chlorides are dimerized to biaryls (2 ArCOCl —> ArAr) by treatment with a disilane RsSiSiRs and a palladium catalyst." " ... 

It was not until Cazin and co-workers introduced the well-defined dimer complex [Pd( J,-Cl)(Cl)(SIPr)]2 that the Kumada-Tamao-Corriu cross-coupling between severely sterically hindered partners was pursued, allowing the synthesis of tri- and tetra-orf/io substituted biaryls [81] (Scheme 6.20). 

To access the calphostins, (S)-16 was subjected to Mitsunobu conditions followed by the two-step dimerization protocol (lithiation, FeCl3) resulting in biaryl (R)-17 as the major diastereomer (Scheme 7.2). In this case, the relative stereochemistry matched the stereochemistry of calphostins A and D. Elaboration following the same protocol as for 5 completed the first total synthesis of calphostin D (4d). Calphostin A (4a) was also synthesized via benzoate protection of the secondary alcohols. 

When (V-acetylprimaquine (175) was incubated for prolonged periods of time with Candida tropicalis (ATCC 20021) (232) and Streptomyces rimosus (ATCC 23955) (233), two unusual minor dimeric metabolites were obtained. These were identified as the methylene-linked compound 177 formed by C. tropicalis and the biaryl-linked compound 178 formed by 5. rimosus. Both dimeric metabolites were prepared synthetically to confirm their identities. 

The low yields in the synthesis of electron-rich biaryls, which are the more frequently occurring natural biaryl targets, are clearly a limitation to this procedure. Further side reactions may arise from hydro-dehalogenation without biaryl coupling, and from intermolecular reactions, leading to dimers or oligomers34,35. 

Biaryls (8, 478-479). The details for oxidative dimerization of arcnes containing electron-donating groups to biaryls with Tl FA have been published. Lead tetraacetate and cobalt(III) fluoride are equally effective reagents.1... 

Complexes such as (6) have been postulated as intermediates in the PdCl2-catalyzed dimerization of arenesulfinic acids or their sodium salts to give the corresponding organic biaryls.36... 

Biaryls have also been prepared by coupling support-bound aryl halides with aryl-zinc compounds (Figure 5.20) or with aryl(fluoro)silanes [203]. As with Suzuki or Stille couplings, these reactions also require transition metal catalysis. An additional strategy for coupling arenes on solid phase is the oxidative dimerization of phenols (Figure 5.20). 

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... 

Oxidative dimerization of A,A-dialkyl-<9-(8-lithio-7-quinolyl)carbamates with anhydrous ferric chloride has been shown to be efficient for the preparation 1,1 -dioxygenated 8,8 -biquinolyls (Scheme 61) and it is anticipated that this tandem halogen-dance oxidative dimerization reaction will find further applications for the synthesis of other highly substituted biaryl molecules.96... 

Not many catalyzed processes involving free radicals are known with these metals. Some vanadium-catalyzed pinacol coupling reactions were developed (reviews [129, 171], [172, 173] and cited ref, [174]). Niobium and tantalum complexes were applied in pinacol coupling reactions [130]. Vanadium(IV) [175-179] and vanadium(V) ([129], reviews [180-186]) complexes are known to catalyze asymmetric oxidative dimerizations of phenols and naphthols in moderate to excellent ees applying oxygen as the terminal oxidant. Biaryls are accessible by intramolecular coupling of sodium tetraarylborates, catalyzed by EtOVOCl2 in the presence of air [187]. 

Detailed electrochemical studies on the synthesis of biaryls from the electrogenerated Ni°(dppe)-catalyzed dimerization of bromobenzene has implicated the steps in Scheme 4, involving Ni(I) and Ni(III) as well as Ni(II) and Ni(0) as being critical to the coupling256. 

Wulff and co-workers observed that the oxidative dimerization of 147 can be accomplished extremely efficiently when it is melted in a sealed tube in the presence of air, to furnish the biaryl product 148, a precursor to the natural compound gossypol (149) (Scheme 35) [99]. The same reaction with iron(III) chloride gives low yields and a less clean product distribution. It is interesting to note that in the case of 3-phenyl-l-naphthol (150), the regioselectivity of the iron(III) chloride-mediated oxidation is completely different from that observed with 02 as the oxidant, with the para-para-coupled product 152 being favored. This air oxidation procedure is also applicable to phenanthrol units (e.g. 153 —> 154), giving similarly high yields. 

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