Biaryl synthesis arene arylation

B.iv.e. Biaryl Synthesis by Arylation ofArenes. The intramolecular arylation of arenes on a polymer support to produce a library of phenanthridones has been described in a patent (Scheme 14). ... 

When Pschorr reported more than a century ago on the first intramolecular homolytic aromatic substitution [25], he showed that biaryls could be readily prepared by intramolecular homolytic aromatic substitution using reactive aryl radicals and arenes as radical acceptors. The aryl radicals were generated by treatment of arene-diazonium salts with copper(l) ions. Today, this reaction and related processes are referred to as Pschorr reactions. It was later found that radical biaryl synthesis could be conducted without copper salts by photochemical or thermal generation of the aryl radical from the corresponding diazonium salt [26], Moreover, the reduction of aryl diazonium salts offers another route to generate reactive aryl radicals. Hence, electrochemistry [27], titanium(lll) ions [28], Fe(II)-salts [29], tet-rathiafulvalene [30] and iodide [31] have each been used successfully for the reduction of diazonium salts to generate the corresponding aryl radicals [32]. As an example, the iodide-induced cycUzation of diazonium salt 6 to phenanthrene derivative 7 is presented in Scheme 13.3 [31]. For further information on the... 

Scheme 10 Regioselective biaryl synthesis by direct arylation of unactivated arenes.

SYNTHESIS OF BIARYLS AND POLY ARYLS BY OXIDATIVE COUPLINGS OF ARENES... 

Campeau L-C, Fagnou K (2006) Palladium-catalyzed direct arylation of simple arenes in synthesis of biaryl molecules. Chem Commun 1253-1264... 

Palladium-catalysed direct arylation of simple arenes in the synthesis of biaryl molecules , Campeau, L.-C. and Fagnou, K., Chem. Commtm., 2006, 1253. 

Table 3. Synthesis of biaryls by arylation of arenes with arylboronic acid under an influence of manganese(III) acetate [9]...

Additional useful access to axially chiral biaryls is the diastereoselective intramolecular palladium-catalysed arylation of arenes with aryl halides. Bringmann s group has employed this reaction in the key-step of the synthesis of naphthyl... 

In a handful of cases, two CCXIH groups have been activated for the synthesis of biaryls. Larrosa and coworkers reported for the first time the decarboxylative homocoupling of aromatic acids mediated by Pd and Ag [62a]. The reaction makes use of Pd(TFA)j as a catalyst and Ag CO as an additive to afford the desired biaryls in 76-95% yields. The only by-products observed were due to the proto-decarboxylation of the aryl carboxylic acid. Both metals are essential for the reaction, and the role of the Ag salt is not only as the terminal oxidant but also as a mediator of the decarboxylation process. The method is subject to some limitations on the substituents on the benzoic acids. Thus, m- and p-nitrobenzoic acids as well as benzoic acids ortho substituted with F, Br, or MeO failed to give decarboxylative homocoupling products. In all cases, protodecarboxylations to the corresponding arenes were the main products observed. The same problem was reported in the protocol developed by Deng and coworkers, where the best results were obtained with PdCl and PPhj in the presence of Ag COj [62b]. 

The Suzuki coupling of aryl boronic acids is a widely used method for the synthesis of functionalized arenes, including biaryls (Scheme 2.86). orfAo-Metallation can be an effective method for introduction of the boronic acid group. 

Kita and coworkers developed an efficient synthesis of aiyl(phenyl)iodonium tosylates from HTIB and arenes in TFE at room temperature [29, 30]. This type of iodonium salt is chemoselectively employed in metal-free syntheses of biaryls (see Sect. 4.2.1). The synthetic strategy has been employed, for example, in the synthesis of polyfluorinated At21X [81] and acid-labile boron-substituted diaryliodonium salts firom aryl boronates with HTIB or the reagent combination PIFA/AcOH (Scheme 4a) [82]. Suna and coworkers have recently described the synthesis of heteroaryl(aryl)iodonium salts from heteroarenes and [hydroxy(tosyloxy)iodo] mesitylene or DIB combined with TsOH or AcOH. The salts were either isolated or used in situ (see Sects. 3.1.2 and 3.2.2) because of their relative instability [83, 84]. (Diacetoxyiodo)arenes were recently combined with electron-donating arenes and trimethylsilyl triflate (TMSOTf) to provide unsymmetric iodonium trifiates without the need for acid addition [85]. 

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