Biaryls formation

Scheme 1 Arylcopper-copper bromide aggregates and biaryl formation.

The biaryl formation is likely the result of more complex processes, involving probably intermediary species such as ArCo1 coming from the reduction of ArConX (equation 58). 

In a simple strategy to biaryl formation, Han et al.89 showed that silicon-directed ipso-substitution and concomitant cleavage from supports could be used for formation of functionalized biphenyls. For this they used a tethered silyl aryl bromide in a Suzuki cross-coupling reaction, followed by the ipso-substitution/cleavage step (Scheme 39). A variety of boronic acids were coupled in this manner. The only difficulty occurred with electron-deficient nitrophenylboronic acid where the desired product was formed under anhydrous conditions in only 33% yield (the remainder being starting material). Reversion to the more usual conditions of aqueous base-DME (i.e., those used by Frenette and Friesen)70 improved the yield to 82%. 

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

Thermal decomposition of diazo ethanoates in an aromatic solvent leads to biaryl formation by attack of aryl radicals on solvent. 

Moreover, the rate of transmetalation must be in accord with this scenario. Sila-nols work best because they undergo transmetalation fast enough to avoid prior cyclopalladation (faster than boronic acids which fail to induce catalytic Cycle 2, affording 6), however at the same time not fast enough to favor a second transmetalation and biaryl formation over desired pathway to the phenyl-substituted complex (cf. 7, catalytic cycle 1 phenyl stannanes, for example, form biphenyl as major product.). 

During their work on the arylation of aromatic compounds by substitution, Fujiwara, et al. observed biaryl formation when aromatic compounds were placed in the presence of olefin-palladium complexes and silver nitrate.80 Developing this reaction as a method for biphenyl synthesis, these authors showed that the more stable the olefin-palladium complex was, the lower the yield. Ethylene dichloropalladium proved to be the best choice, when used with silver nitrate. However, the reaction required stoichiometric amounts of both catalysts (Scheme 10.47). Benzene derivatives substituted by electron-donating or -withdrawing groups reacted as well, but a mixture of regioisomers was produced, except for nitrobenzene, which only gave m,m -dinitrobiphenyl. 

It is also likely that radical cation formation occurs in reactions of very reactive arenes with Pd(II) (see Section II.B.3.b), which would also lead to biaryl formation. That the reactions of arenes with Pd(II) compounds are far from simple is illustrated by the work of Arzoumanidis and Rauch.573,574 In the reaction of Pd(02CCF3)2 with benzene or naphthalene in TFA, a variety of polynuclear complexes, containing both Pd(I) and Pd(II) and arenes, were isolated574 in addition to the usual biaryls. 

Arylmercury(II) compounds have been shown575 to undergo substitution by Pd(II) salts with subsequent biaryl formation. The following mechanism was suggested ... 

In the presence of oxygen, the formation of biaryls by Pd(II) oxidation of arenes can be made to be catalytic in palladium.576 For example, toluene with Pd(OAc)2 and 02 at 150°C for 16 hr afforded bitolyls in 20,600% yield based on palladium. It was concluded that biaryl formation in these systems occurs via free aryl radicals.576 The role of homolytic processes in these reactions is not clear, and further clarification of the mechanism is desirable. 

Scheme 1. The essentials of biaryl formation by oxidative coupling of arenes.

Scheme 9. Removable tether strategy for biaryl formation.

Scheme 28. Lead(IV)-mediated oxidation (Wessely reaction) of a simple gallic acid derivative without biaryl formation.

Biaryl formation is important when cationic substrates are used, such as diazonium salts (usually in the intramolecular version, the photo-Pschorr reaction [113]) or quaternary ammonium salts [114], In this case PET generates a neutral radical, and this expels nitrogen or an amine molecule yielding an aryl radical. Although the present discussion generally does not include ma-... 

Biaryl formation using Stille coupling suffers from the problem of by-product formation, which is apparently due to ligand exchange between palladium and phosphorus subsequent to oxidative addition of the aryl halide to palladium (Scheme 4-35). A detailed paper dealing with this phenomenon has appeared [128]. In unfavorable cases the required biaryl can be the minor product. 

Palladium, in the form of palladium(II) acetate, has also been used to catalyze biaryl formation directly from aryl iodides (R3N 100 °C), especially P-NO2 and p-Cl derivatives. As usual, ortho substituents severely hinder this type of coupling. Related reductive couplings of aryl halides have been achieved using hydrazine and a Pd-Hg catalyst, electrochemically generated Pd° catalysts, or a palladium on carbon catalyst in the presence of aqueous sodium formate, sodium hydroxide and, crucially, a catalytic amount of a surfactant. The first two procedures look to be particularly selective and efficient, while the latter, rather different, method is not so efficient but does look amenable to large scale work. 

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