Aromatic compounds biaryls, synthesis

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. 

The carboxylates of indium and thallium are obtained by dissolving the oxides in acid. Acetate and trifluoroacetate salts are used extensively as reagents in organic synthesis. Certain other thallium compounds have been used also. The trifluoroacetate, T1(02CCF3)3, will directly thallate aromatic compounds to give arylthal-lium species, for example, C6H5T1(02CCF3)2 (cf. aromatic mercuration, Section 15-15) and oxidize arenes to biaryls. 

This method has been applied to the synthesis of various polycyclic aromatic compounds [91]. Among the interesting applications are lactone formation in the preparation of natural products having biaryl skeletons (Eq. 42) [87] and double cyclization leading to spirocyclic compounds (Eq. 43) [92] and a fullerene fragment (Eq.44) [93]. 

The two coupling reactions appear to have a common free-radical intermediate. Functional groups already in the aromatic compound, Axil, orient ortbo-para regardless of their nature. The reactions are most valuable for the preparation of biaryls of unequivocal structure when the hydrocarbon, Ar H, is unsubstituted. Good directions are given for the synthesis of p-bromobiphenyl (35%), and the literature of the reaction has been reviewed. Among the hydrocarbons prepared in this way are a- and yS-phenylnaphthalenes, o-, m-, and p-methylbiphenyls and m- and p-terphenyls. Thiophene and pyridine nuclei also have been aryl-ated. ... 

Aryllead tricarboxylates have been shown to react in trifluoroacetic acid with a range of aromatic compounds to give biaryls [31c]. With aromatic compounds that are more electron-rich than toluene the yields are generally good and the method is a useful synthesis of unsymmetrical biaryls (Scheme 13.18). It has been reported that a cationic intermediate generated from aryllead tricarboxylates was probably involved. 

Organocopper reagents, such as methylcopper prepared from MeLi were also used as catalyst recently [148]. Yields could be further improved by ultrasonic irradiation [149],.as well as under phase transfer conditions [150]. It is surprising that, in contrast to the Ullmann biaryl synthesis, activated aromatic fluoro compounds (e.g. fluoro-esters, -nitrils, -aldehydes and -acetophenones) can couple with phenols in good yield. The reaction does not require any catalysts, but only K2CO3 as a base, [146] (Scheme 56). ... 

Electron-rich aromatic compounds may be coupled to biaryls under the action of T1(0C0CF3)3, and the utility of this approach is illustrated in the synthesis of... 

The arylation of aromatic compounds with aryldiazonium salts (III) in the presence of base affording biaiyls (II) is called the Gomberg-Bachmann-Hey (GBH) reaction [46]. First observations were published by Bamberger [47] and Kuhling [48] more than a century ago. However, the first practical synthesis of biaryls was discovered by the former authors, and was further developed by Hey. The original... 

An interesting chemical oxidative methodology, first reported many years ago (the Scholl reaction), has gained significant interest in recent years, due to its potential in the synthesis of several TT-conjugated materials. This reaction is an intramolecular oxidative C—C bond formation, mediated by various metal-based oxidants, between two benzenoid rings to produce a biaryl linkage and it has been extensively utilized for the synthesis of planar polycyclic aromatic compounds. 

In this chapter, the intermolecular multicomponent aromatic ring construction reactions and intramolecular single-component aromatic ring construction reactions are described. Among them, the [2+2+2] cycloaddition and intramolecular hydroarylation reactions are the most widely employed and reliable method. Various polycyclic and sterically hindered aromatic compounds have been synthesized by this method. In the past 10 years, the asymmetric [2+2+2] cycloaddition and intramolecular hydroarylation reactions have been developed, which enabled the enantioselec-tive synthesis of sterically hindered chiral aromatic compounds, such as axially chiral biaryls, planar chiral cyclophanes, and helically chiral heUcenes. Details of the transition metal-mediated aromatic ring construction reactions are comprehensively covered in the recently published book... 

Perhaps the most important preparative use of aryl free radicals is in the synthesis of biaryls. If an aryl free radical is generated in the presence of a second aromatic compound, substitution leading to the biaryl is observed. Yields in this... 

Importantly, asymmetric variants of the foregoing reactions have been developed by using the cationic or neutral rhodium(I)/axially chiral biaryl bisphosphine complexes as catalysts. Although the rhodium-based catalysts are expensive, these are highly stable and can be handled readily using conventional laboratory equipment. Therefore, I believe that rhodium-catalyzed [2 - - 2 - - 2] cycloaddition reactions wiU be employed continuously for the synthesis of complex aromatic compounds. 

Preparation of the chiral biphenyls and binaphthyls with high enantiose-lectivity can be achieved via substitution of an aromatic methoxyl group with an aryl Grignard reagent using oxazoline as the chiral auxiliary.38 Schemes 8-10 and 8 11 outline the asymmetric synthesis of such chiral biaryl compounds. 

T1 resin traceless linker [131-134], synthesis of phenols [135], biaryls, alkyl arenes [136, 137], azides [138], aromatic hydrazines, halides [cf. 128, 129, 139], ester, azo compounds, cinno-lines [140], benzotriazoles [141]... 

More recent studies, however, have proved that these anions, mainly di-7-butyl substituted phenoxides and 1- and 2-naphthoxide ions, are excellent nucleophiles under electrochemical or photostimulated conditions. These anions behave as bidentate nucleophiles and couple with radicals through the carbons of their aromatic ring. This has been proved to be a powerful route to biaryls unsymmetrically substituted by EWG and electron-acceptor groups, which are of interest in non-linear optics, as well as in the synthesis of cyclic compound (Section V.E.2). 

In aromatic systems, oxazolines can have three different functions (Fig. 4). Firstly, they can be used as protecting groups for carboxylic acids. Secondly, they activate even electron-rich aromatic systems for nucleophilic substitution. Fluorine or alkoxy groups in the ortho position can be substituted by strong nucleophiles such as Grignard reagents. Thirdly, when biaryl compounds with axial chirality are synthesized in these reactions, oxazolines can induce the formation of only one atropisomer with excellent selectivity. These three qualities were all used in the synthesis of 20, a precursor of the natural product isochizandrine [10]. 

Quinolinyl moiety has been applied in the Negishi reaction either as an electrophile or as nucleophile. 2- or 4-substituted quinolinyl triflates or bromides have been used extensively for introduction of aromatic rings at the C2 or C4 positions of the heterocycle. In a representative example, Murata et al. employed a Negishi reaction in his effort toward the formal synthesis of antitumor compound camptothecin. In accordance to that, 2-chloropyridine was allowed to react with lithium naphthalenide, followed by zinc chloride, to afford the corresponding zinc pyridine salt. Reaction of the resulting organozinc intermediate with 2-chloro-3-quinoline carboxylate provided the hetero biaryl core of camptothecin. ... 

Exactly the same method was successfully employed in the synthesis of 2,2 -bipyridines bearing a free amino group. Thus 4,4 -diamino-2,2 -bipyridine was prepared from 5-amino-2-chloropyridine in 60% yield, respectively [38]. Nickel-catalysed synthesis of biaryls and related vinyl halides were successfully used in a great number of examples [39,40], including the strained aromatic ether-sulfone oligomers [41]. For instance, compound 84 was cyclized to a very strained cyclic... 

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