Biaryls from aryl halides

Recently, chloro-, bromo-, and iodoben-zenes have been subjected to electroreduction using Ni(0) complex mediators to yield biphenyl. NiCl2L2 and NiBr2L2 [L= P(Ph)3, (Ph)2PCH2CH2P(Ph)2] have been used as catalysts [259-265]. Pro-tic media such as alcohols, that is, methanol, ethanol or alcohol-water mixtures are found to be suitable solvents for achieving the electrosynthesis of biaryls from aryl halides according to a procedure that involves a catalytic process by nickel-2,2 -bipyridine complexes [266]. Electrochemical cross-coupling between... 

Additional procedures which produce biaryls from aryl halides include catalytic hydrogenation, the action of the binary mixture magnesium-magnesium iodide, and the use of powdered iron in hydroxylated media. ... 

TABLE 3. Preparation of Biaryls from Aryl Halides Using Sodinm Formate, Pd/C, and Snrfactant in Sodinm Hydroxide Liqnor ... 

Table 2. Synthesis of biaryls from aryl halides catalysed with Ni(PPh3)4 prepared by electrochemical reduction [25]...

Copper-based methods for synthesis of biaryls from aryl halides may become dominant in the future research. 

The Suzuki-Miyaura reaction is widely used to form biaryls from aryl halides and arylboronic acids. The reaction involves oxidative addition of the palladium to the aryl halide, followed by reaction with base, transmetallation with the boronate and... 

The direct preparation of arylboronic esters from aryl halides or triflates now allows a one-pot, two-step procedure for the synthesis of unsymmetrical biaryls (Scheme 1-41) [147]. The synthesis of biaryls is readily carried out in the same flask when the first coupling of the triflate with diboron 82 is followed by the next reaction with another triflate. The synthesis of naturally occurring biflavanoids and the couphng of N-(phenylfluorenyl)amino carbonyl compounds to polymeric supports are reported [154]. 

Biaryl synthesis from aryl halides is a more interesting reaction due to the value of these molecules and their difficult access by chemical methods. The first electrosyntheses were simultaneously done in 1979-80 by three groups [21-23] who used NiCljPPha (1-20%) as catalyst precursor in the presence of excess PPhs. Later, several groups investigated the use of bidentate phosphines like dppe associated with nickel in the synthesis of various biaryls, and notably 2,2 -bipyridine and of 2,2 -biquinoline from respectively 2-chloropyridine and 2-chloroquinoline [24], More recently new nickel complexes with l,2-bis(di-2-alkyl-phosphino)benzene have been studied from both fundamental and synthetic points of view [25]. They have been applied to the coupling of aryl halides. 

Cross coupling. Biaryls are obtained from aryl halides and aryl(halo)silanes in the presence of the palladium complex and KF. 

Apart from aryl halides, other very easily available substrates for nickel-catalysed biaryl (II) synthesis are aryl sulfonates (XII). Method D is very efficient in the homocoupling reactions of substituted aryl sulfonates in good to excellent yields [15], Table 6. Substituted aryl sulfonates are readily obtained from phenols and trifluoromethanesulfonic anhydride, benzenesulfonyl-, tosyl- or methanesulfonyl chloride in pyridine, or in a suitable inert solvent such as dichloromethane in the presence of triethylamine or Hiinig s base. Among other nickel complexes, Ni(dppe)Cl2 and Ni(dppf)Cl2 have been used (10 mo1%) as slightly less versatile catalysts for the homo-couplings of naphthyl sulfonates in refluxing THF, DMF or their mixtures [42]. 

Ready availability of arylboronic esters from aryl halides or triflates (Eqs. 13 and 14) now offers a one-pot, two-step procedure for synthesizing unsymmetrical biaryls. The cross-coupling reaction of bis(pinaco-lato)diboron with triflate in dioxane is followed by a subsequent coupling with another triflate in the presence of K3PO4 to furnish an unsymmetrical biaryl from two triflates (Eq. 63). The synthesis from two different... 

Arylcopper intermediates can be generated from organolithium compounds, as in the preparation of cuprates.95 These compounds react with a second aryl halide to provide unsymmetrical biaryls in a reaction that is essentially a variant of the cuprate alkylation process discussed on p. 680. An alternative procedure involves generation of a mixed diarylcyanocuprate by sequential addition of two different aryllithium reagents to CuCN, which then undergo decomposition to biaryls on exposure to oxygen.96 The second addition must be carried out at very low temperature to prevent equilibration with the symmetrical diarylcyanocuprates. 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

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