Unsymmetrical biaryls

A number of methods, all catalyzed by palladium complexes, have been used to prepare unsymmetrical biaryls (see also 13-14). In these methods, aryl bromides or... 

Another free-radical arylation method consists of the photolysis of aryl iodides in an aromatic solvent. Yields are generally higher than in 14-17 or 14-21. The aryl iodide may contain OH or COOH groups. The mechanism is similar to that of 14-17. The aryl radicals are generated by the photolytic cleavage ArI AR + T. The reaction has been applied to intramolecular arylation (analogous to the Pschorr reaction). A similar reaction is photolysis of an arylthallium bis(trifluoroacetate) (12-21) in an aromatic solvent. Here too, an unsymmetrical biaryl is produced in good yields. ... 

Unsymmetrical coupling of vinylic, alkynyl, and arylmercury compounds was achieved in moderate-to-good yields by treatment with alkyl and vinylic dialkylcopper reagents (e.g., PhCH=CHHgCl -t- Mc2CuLi PhCH=CHMe). Unsymmetrical biaryls were prepared by treating a cyanocuprate ArCu(CN)Li (prepared from ArLi and CuCN) with an aryllithium Ar Li. ... 

The Stille reaction has developed as a popular protocol for the formation of C-C bonds due to the air- and moisture-stability as well as functional group compatibility of organotin compounds. Together with the Suzuki-Miyaura coupling it is one of the most powerful methods for the synthesis of molecules containing unsymmetrical biaryl moieties. However, despite its efficiency, this versatile reaction has slowly been displaced by other procedures that avoid the use of highly toxic organostannanes. 

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]. 

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. 

Substituted unsymmetrical biaryls can be readily obtained from 6-aryl-3-cyanopyran-2-ones on treatment with acetone and a base. Initial nucleophilic attack at C-2 is followed by a C-C cyclisation (Scheme 38) <00JCS(P1)37I9>. 

Pershichini 2003 Kotha et al. 2002), which is by far the most versatile synthetic method available for the generation of unsymmetrical biaryl compounds and so was an obvious target for the development of flow... 

SYNTHESIS OF UNSYMMETRICAL BIARYLS USING A MODIFIED SUZUKI CROSS-COUPLING 4-BIPHENYLCARBOXALDEHYDE ([1,1 -Biphenyl]-4-carboxaldehyde)... 

Unsymmetrical biaryls, notably those having both an electron-releasing and an electron-withdrawing group, have interesting physical properties in the field of... 

So far a high selectivity in the electrochemical synthesis of unsymmetrical biaryls has only been obtained in two-step processes. 

This was done, for example, with a Pd-PPha complex used stoichiometri-cally as outlined in Eq. 7 [28, 37, 54]. The electrochemically generated Pd° complex first reacts with one aryl halide. The electroreduction of this cr-Pd-complex in the presence of the other aryl halide affords the unsymmetrical biaryl in good yield ... 

Decomposition of this equilibrium mixture with catalytic amounts of CuOTf affords a mixture of all three possible biaryls. The formation of the unsymmetrical biaryl 2-Me2NCH2C6H4C6H4Me-4 can only be explained by the occurrence of aggregated copper species in which both the C6H4CH2NMe2-2 and the C( H4Me-4 groups are bound to the same copper core [77]. It was furthermore observed that the ratio of the formed biatyls is not statistical, which points to significant differences in the thermodynamic stabilities of the various mixed aggregates present in solution. 

Constitutionally Unsymmetrical Biaryls by Nucleophilic Aromatic Substitution... 

The procedure described above is based on a paper reporting the Ni- or Pd-catalyzed reaction of arylzinc derivatives with aryl halides. The Ni- or Pd-catalyzed cross coupling reaction represents one of the most general and satisfactory routes to unsymmetrical biaryls. 

Unactivated aryl iodides undergo the conversion Arl — ArCHj when treated with tris(diethylamino)sulfonium difluorotrimethylsilicate and a palladium catalyst.131 A number of methods, all catalyzed by palladium complexes, have been used to prepare unsymmetrical biaryls (see also 3-16). In these methods, aryl bromides or iodides are coupled with aryl Grignard reagents,152 with arylboronic acids ArB(OH)2,153 with aryltin compounds Ar-SnR3,154 and with arylmercury compounds.155 Unsymmetrical binaphthyls were synthesized by photochemically stimulated reaction of naphthyl iodides with naphthoxide ions in an SrnI reaction.156 Grignard reagents also couple with aryl halides without a palladium catalyst, by the benzyne mechanism.157 OS VI, 916 65, 108 66, 67. 

The coupling of aryl halides with copper is called the Ullmann reaction.m The reaction is of broad scope and has been used to prepare many symmetrical and unsymmetrical biaryls.187 When a mixture of two different aryl halides is used, there are three possible products, but often only one is obtained. For example, picryl chloride and iodobenzene gave only 2,4,6-trinitrobiphenyl.188 The best leaving group is iodo, and the reaction is most often done on aryl iodides, but bromides, chlorides, and even thiocyanates have been used. 

Unsymmetrical biaryls.14 The Pd(0)- or Ni(0)-catalyzed coupling of arylzinc derivatives with aryl halides appears to be the method of choice for synthesis of unsymmetrical biaryls (equation I). Both Pd[P(C6H5)3]4 and Ni[P(C6H5)3]4 are usually equally effective with aryl iodides, but only activated aryl bromides can be coupled with Pd(0). 

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