Aryl homocoupling

Abstract This chapter highlights the use of iV-heterocyclic carbenes as supporting ligands in arylation reactions different than the more common cross-coupling reactions, including C-F bond activation, catalytic arylation, homocoupling, direct arylation and oxidative Heck reactions. 

A convergent synthetic route to the highly symmetrical biphenylene dimer 61 was implemented based on a stepwise connection via an aryl-aryl homocoupling reaction. As can be seen in Scheme 5.9, after the lithiation of 1,3-dibromo-2-iodobenzenes 62 in diethyl ether, the resulting aryllithium was oxidized with CuBr2 to give the corresponding 2,6,2, 6 -tetrabromobiphenyls 63. Upon... 

Three oxidative reactions of benzene with Pd(OAc)2 via reactive rr-aryl-Pd complexes are known. The insertion of alkenes and elimination afford arylalk-enes. The oxidative functionalization of alkenes with aromatics is treated in Section 2.8. Two other reactions, oxidative homocoupling[324,325] and the acetoxylation[326], are treated in this section. The palladation of aromatic compounds is possible only with Pd(OAc)2. No reaction takes place with PdCl2. 

Traditionally, the synthesis of symmetrical biaryls was routinely accomplished using the Ullmann reaction. Recently, palladium-catalyzed homocoupling of aryl halides has also been demonstrated to rival the utility of the Ullmann coupling. As illustrated in Scheme 21, using Pd(OAc)2 as the... 

Ni(0)-mediated homocouplings of 2-subslituted l,4-phcnylenebis(triflate)s have been reported by Percec et al. [15] to provide substituted poly(/ -phenylene)s 7 containing alkyl, aryl or ester substituents in the 2- and 3-positions of the 1,4-phenylcnc skeleton. This method of preparation appears to be broad in scope, especially due to the ease of preparation of the bis(lriflatc) monomers starting from the corresponding hydroquinone derivatives. 

The use of imidazolium salts for in situ catalyst formation was shown to be optimal for the coupling of TMS-protected alkynes even with sterically demanding aryl bromides and avoids the formation of homocoupling-derived products. For this reaction, Nolan reported that the activation of chlorobenzene by this catalytic system was possible in moderate yield [125] (Scheme 6.41). 

The homocoupling of aryl halides and triflates can be made catalytic in nickel by using zinc as a reductant for in situ regeneration of the active Ni(0) species. 

The homocoupling of aryl halide to diaryl compounds, known as Ull-mann coupling, is a synthetically useful reaction and has wide applications in material research. Such couplings have been studied in aqueous conditions. In 1970, arylsulfinic acids were coupled with Pd(II) in aqueous solvents to biaryls (Eq. 6.25).53 However, the reaction required the use of a stoichiometric amount of palladium. In the presence of hydrogen gas, aryl halides homocoupled to give biaryl compounds in moderate yields (30-50%) in an aqueous/organic microemulsion (Eq. 6.26).54... 

In addition, arylthiophene 70 was obtained by a one-pot Suzuki coupling of p-methoxyiodobenzene and 3-bromothiophene via an in situ boronate formation using one equivalent of the thermally stable diborane 69 [55], This method avoids the isolation of boronic acids and is advantageous when base-sensitive groups such as aldehyde, nitriles and esters are present. However, the cross-coupling yields are low when both aryl halides are electron-poor because of competitive homocoupling during the reaction. 

Homocoupling of aryl acetic acid derivatives has been achieved by deprotonation and oxidation by I2 as outlined... 

It was shown a few years ago that a-haloesters can react with an aryl-nickel compound generated electrochemically in a divided cell (Eq. 8) [57]. The main drawback for this two-step method is the use of a large excess of PPhs to prevent the homocoupling reaction ... 

Homocoupling of aryl halides in the presence of Cu or Ni or Pd to afford biaryls. 

A second example from the same group is the synthesis of an elaborate diethynyltriphenylene derivative (Scheme 7 Table 8,entries 12,13) [58].Zn/Pd-promoted homocoupling of a 4-iodo-l,2-dialkoxybenzene furnishes the desired tetraalkoxybiphenyl, an electron-rich aromatic system. Iron trichloride-catalyzed Friedel-Crafts arylation of the biphenyl derivative with dimethoxy-benzene furnishes an unsymmetrical triphenylene derivative. Deprotection, oxidation, and subsequent Diels-Alder reaction with cyclohexadiene is followed by catalytic hydrogenation and reoxidation. TMS-CC-Li attack on the quinone delivers the alkyne modules, treatment with SnCl2 aromatizes the six-mem-bered ring, while KOH in MeOH removes the TMS groups cleanly to give the elaborate monomer. 

A similar cross-coupling reaction between triarylbismuth(V) compounds and aryl-, heteroaryl-, or styryltributylstannanes smoothly proceeded under the same reaction conditions as those for the iodonium salts (Scheme 17) [34]. Homocoupling side products were not mentioned. 

Symmetrical biaryls are important intermediates for synthesising agrochemicals, pharmaceuticals and natural products (1). One of the simplest protocols to make them is the Ullmann reaction (2), the thermal homocoupling of aryl chlorides in the presence of copper iodide. This reaction, though over a century old, it still used today. It has two main disadvantages, however First, it uses stoichiometric amounts of copper and generates stoichiometric amounts of CuL waste (Figure 1, left). Second, it only works with aryl iodides. This is a problem because chemicals react by their molarity, but are quantified by their mass. One tonne of iodobenzene, for example, contains 620 kg of iodo and only 380 kg of benzene . 

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