Arene oxidative coupling

Arene coordination to Pd is invoked in the arene C-H bond activation and arene oxidative coupling by cationic Pd(ll) complexes. 

The oxidative coupling of thiophene, furan[338] and pyrrole[339,340] is also possible. The following order of reactivity was observed in the coupling of substituted furans[338] R = H > Me > CHO > CO Me > CH(OAc)i > CO2H. The cross-coupling of furans and thiophenes with arene is possible, and 4-phenylfurfural (397) is the main product of the cross-coupling of furfural and benzene[341]. 

As expected, reaction of A-aroylpyrroles 28 in the absence of added arene affords the bipyrroles 29 or cyclized product 30 [32, 33], Bipyrrole 31 was prepared via this oxidative coupling reaction [32],... 

Diarylamides with arenes activated by electron-donating substituents can be converted to azacycles by anodic oxidation through phenolic oxidative coupling reactions that can be a key step in the synthesis of alkaloids (Schemes 16 and 17). According to the nature of substituents and the experimental conditions, either spiro compounds [22] or non-spiro compounds [23, 24] were obtained. 

A molybdenum-mediated oxidative coupling of aniline 1 with cyclohexene 2a provides carbazole 3. Alternatively, the same overall transformation of aniline 1 to carbazole 3 is achieved by iron-mediated oxidative coupling with cyclo-hexa-1,3-diene 2b or by palladium-catalyzed oxidative coupling with arenes 2c. The use of appropriately substituted anilines and unsaturated six-membered hydrocarbons opens up the way to highly convergent organometallic syntheses of carbazole alkaloids. 

Utilization of oxidative coupling reactions has been reported (74AG(E)291,78AG(E)755) for the construction of novel heterocyclic arenes such as (18). 

The use of hypervalent iodine reagents in carbon-carbon bond forming reactions is summarized with particular emphasis on applications in organic synthesis. The most important recent methods involve the radical decarboxylative alkylation of organic substrates with [bis(acyloxy)iodo]arenes, spirocyclization of para- and ortho-substituted phenols, the intramolecular oxidative coupling of phenol ethers, and the reactions of iodonium salts and ylides. A significant recent research activity is centered in the area of the transition metal-mediated coupling reactions of the alkenyl-, aryl-, and alkynyliodonium salts. 

In the non-phenolic oxidative coupling reaction the electron-rich arene 19 undergoes electron transfer yielding the radical cation 20, which is preferably treated in chlorinated solvents or strongly acidic media. Attack of 20 on the electron-rich reaction partner 21 will proceed in the same way as an electrophilic aromatic substitution involving adduct 22 which extrudes a proton. The intermediate radical 23 is subsequently oxidized to the cationic species 24 which forms the biaryl 25 by rearomatization. In contrast with the mechanism outlined in Scheme 5, two different oxidation steps are required. 

A more general and efficient approach to alkynyl carboxylates, also thought to involve alkynyliodonium carboxylate intermediates, entails the treatment of bis(acyloxyiodo)-arenes with alkynyllithium reagents (equation 88)81. These reactions are best conducted in the presence of 2-nitroso-2-methylpropane in order to suppress oxidative coupling of the lithium acetylides by the acyloxyiodanes. 

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

It is difficult to make generalizations about the oxidative coupling of arenes, given the number of possible mechanisms. Factors that influence the reaction course include the oxidation potential of each aryl unit, the substitution pattern, the solvent system, and the oxidation reagents themselves. Optimization then becomes a case-by-case effort in order to obtain the best selectivities and the best yields. Nevertheless, results over the last decade have... 

Oxidative coupling was used to form alkyl- and alkoxy-substituted phenanthrenedione products lOOa-d (Table 22) [73]. These compounds can be obtained by other methods, albeit in much lower yields. In this instance, oxidative coupling proceeds even with carbonyl-substituted arenes, and VOF3 gives much better results than thallium- or palladium-mediated coupling procedures. 

As can be seen in the scheme below, a series of substituted 2-(2-aminothiazol-4-yl)-benzo[ ]furans with inhibitory activity for leukotriene B4 were made from benzofurans via acylation, followed by Hantzsch thiazole formation <070BC3083>. 2-Substituted benzo[ ]furans could also be generated via an aerobic oxidative coupling of 2-unsubstituted benzo[ ]furans with arenes through the palladium-catalyzed double C-H activation <07OL3137>. In addition, 2,3-diarylbenzo h I uran could be constructed by a palladium-catalyzed arylation of benzo[6]furan with an aryl chloride in the presence of a bulky, and electron-rich phosphine <07OL1449>. 

Biaryls. Biaryls can be prepared by oxidative coupling of arenes with palladium(II) compounds, but the coupling is not regioselective. Regioselectivity is considerably improved by use of TTFA as oxidant and only catalytic amounts of Pd(OAc),. Formation of 4,4 -biaryls is favored from arenes substituted with either electron-donating or moderately electron-withdrawing substituents. The first step is thallation to form ArTlfOCOCF,)-. Example ... 

Aryl C-H bonds are known to be active and thns benzenes undergo auration, which has been exploited as the oxidative coupling of arenes. ... 

Ortho,ortho -coupling of the phenoxy radical produces V, its further oxidation forms via an arene oxide the benzofuran VI, and the ortho, para -coupling leads after a subsequent Michael addition to the Pummerer ketone VII. 

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