Biaryl phenol coupling

Biaryl phenol coupling.1 The natural dibenzylbutanolide lignans, prestegane A (la) and B (lb), are converted to the corresponding bisbenzocyclooctadiene lactones (2) by oxidation with Ru02 in TFA-TFAA in 80-85% yield. The usual reagent for this oxidation, thallium tris(trifluoroacetate), is less efficient (45-50% yields). 

In connection with another project being developed we needed large quantities of a biaryl phenol or biaryl aryl methyl ether which was being prepared by a Suzuki coupling reaction (Scheme 6). 

The Ullmann coupling is the classical example of Cu-catalyzed biaryl coupling, wherein (a) a phenol and arylhalide substrate are converted to a bis-arylether or (b) two arenes are coupled to form a bis-arene species. These coupling reactions are of great importance for general organic synthesis as well as pharmaceutical and fine chemicals. The copper-catalyzed phenol coupling to arrive at chiral biphenol derivatives is used extensively as a test reaction for the catalytic activity of new copper complexes [254,255]. 

Macrocyclic diarylheptanoids can be derived from their open chain congeners by oxidative phenol coupling resulting in macrocyclic biaiyls or biaryl ethers. Usually they were named after the plant source and can be conveniently classified according to the plant families in which they occur. 

One-electron oxidation of an aryl ether, for example at the anode, gives rise to a radical cation whose fate may be radical coupling (shown as dimerization) or substitution into a neutral phenol ether both paths are shown in Scheme 6 and converge to a biaryl product. Other products are possible if coupling at a quaternary center takes place. Mechanisms of this type must operate for the important couplings of phenol ethers with phenol ethers, and phenols with phenol ethers possibly they should not be neglected for phenol-phenol coupling also, in certain cases. 

As mentioned in Section 3, oxidative phenolic coupling plays an important role in the biosynthesis of a wide range of natural products. This stimulated the application of this reaction to the biomimetic synthesis of natural biaryls. Unlike the in vivo processes, very probably following a radical dimerization pathway [91] yields of in vitro syntheses are generally moderate or low. Classical work in this field has been extensively reviewed [92], and important developments after the 70s will therefore be summarised here. 

The use of air-sensitive TTFA was later replaced by its in situ preparation from thallium(III) oxide and TFA [121]. This method represented a new and effective route to biaryls. Conversions were significantly improved, the formation of overoxidized by-products could be decreased and in most cases yields were better than those in classical phenolic couplings or in other previously known methods [122]. Phenolic ethers could also be transformed to biaryls in this way [123] (Scheme 53). The TTFA/ TFA system was occasionally used for the regioselective formation of aryl-aryl bonds [124]. 

A simplification of the classical Baker-Venkataraman 3-step route uses DBU to effect a one-pot synthesis of 2,8-disubstituted chromones <97SYN195>. Solid state phenol coupling of a 2 -hydroxyacetophenone is the key step in a total synthesis of the natural atropisomer of a biflavone <97JOC7222>. An alternative approach involves an asymmetric intramolecular oxidative coupling to produce the biaryl precursor <97TL1087>. 

To form the biaryl ether linkage, a biosynthetic type of oxidative phenolic coupling is used. After trials employing several oxidizing reagents, the best results were obtained with potassium ferricyanide in a two-phase system. Following a diazomethane reaction, low yields of two para coupling products, ( )-cularine (11) and ( )-enneaphylline (9), are obtained. 

Stereospecific phenol coupling. Oxidation of (S)-(+)-7-hydroxy-l,5,6-tri-methyl-l,2,3,4-tetrahydronaphthalenc (1) in ether with K3Fe(CN)e in 0.2 N NaOH at 20 yields the optically active dimer shown to be the (SSytrans-enantiomer (2). The dl-(orm of the biaryl is also the major product of oxidation of (RS)-(l) together with smaller amounts of two diastereomeric forms. It... 

Enantioselective synthesis of axially chiral biaryls include all approaches where the starting material is achiral and the chirality is induced by an influence of chiral catalyst or reagent. Among enantioselective reactions that have been successfully used in the synthesis of axially chiral biaryls are the Kharasch reaction [34-36], Suzuki-Miyaura reaction [37,38], oxidative phenolic coupling mediated by copper complexes... 

Oxidation of phenols and aromatic amines using HRP is generally of little synthetic value, as oligomers and polymers are the main products (5, 260). Under certain conditions oxidative coupling of phenols or naphthols to give biaryls can be achieved, but with low selectivity (262). In contrast, HRP can catalyze a number of useful oxidative N-and 0-deaIkyIation reactions that are relatively difficult to carry out synthetically. This area has been described in detail by Meunier (263). A method for the preparation of optically active hydroperoxides using HRP C has been developed (264). Optically pure (S)-hydroperoxides... 

Murrayafoline A (7) required for this total synthesis was obtained starting from 3-formylindole (618) (577) (see Scheme 5.40). Lead tetraacetate-mediated oxidative non-phenolic biaryl coupling of 7 led to murrastifoline F (191) in 60% yield. The... 

The well-known and widespread phenolic oxidations3 and the related nonphenolic oxidations4-6 for the formation of biaryl linkages are not restricted to the classic cases ofintermolec-ular coupling reactions. There are also examples of intramolecular coupling reactions with the option of performing the reaction stereoselectively, provided that some electronic requirements are fulfilled ... 

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). 

Figure 5.20. Biaryl formation from resin-bound aryl bromides and arylzinc compounds [32,204], and by oxidative coupling of phenols [205],...

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