C-H aryl

The direct arylation of heteroaryls is particularly attractive due to the fact that these moieties are present in many biologically active compounds [58], Recently, etinkaya and co-workers reported the direct arylation of benzoxazoles and ben-zothiazoles with aryl bromides catalysed by a bis-NHC-palladium complex [59], Also, Sames and co-workers have described the C-H arylation of different SEM-protected heteroarenes, catalysed by NHC-Pd complex 28 (Scheme 7.12, pathway a) [60],... 

Several metal cross-coupling reactions have been applied to pyrazoles. C-H Arylation of aryl tosylates or chlorides could be achieved with a ruthenium catalyst at the C-2 phenyl position of... 

When aryl (sp2) and benzylic (sp3) C-H bonds are available, as in 2-(2-tolyl)pyridine, an Si-aryl bond is formed preferentially despite the higher dissociation energy for a C-H aryl bond compared with a benzylic C-H (110 vs. 90kcal mol 1). 

Moreover, in this particular example, the distribution of mono- and bis-silylated products changes over time improved yields of the mono-silylated (sp2-functionalized product) are observed after 1 h reaction, whereas overnight reaction leads to a good yield of bis-C-H aryl- and C-H benzyl-activated product (Equation (55)).ss... 

Intramolecular C-H arylations have been described and are mediated by a variety of palladium complexes, affording a host of heterocyclic products. Carbazoles can be synthesized by a sequential amination/C-H functionalization process (Equation (161)). 

Fig. 50 Pd-catalyzed oxidative C-H arylation using aroyl peroxides...

Aryl or diaryl substituted 3,4-(ethylenedioxy)thiophenes have been prepared by palladium-catalyzed direct C-H arylation of 3,4-(ethylenedioxy)thiophene itself with ary 1/he ternary 1 iodides/bromides <07TL539, 07T10363>, and direct coupling of... 

Phenylazo-1,2,4-triazole were prepared from benzenediazonium chloride and 1,2,4-triazole <07SC1977>. 5-Aryltriazole acyclonucleosides 134 with various aromatic groups on the triazole ring were synthesized from precursor 133 via the Suzuki coupling reaction in aqueous solution and promoted by microwave irradiation <07TL2389>. 1-Methyl-1,2,4-triazole 135 participated in a palladium-catalyzed C-H arylation reaction with 3,5-dimethoxychlorobenzene 136 to give coupled product 137 <07OL1449>. 

In general these methods, developed by Sames for C-H arylation of indoles, do not follow the expected electrophilic regiochemistry, instead showing high C2 selectivity (Scheme 14). Sames described how their mechanistic experiments point towards a mechanism involving electrophilic C-H activation [29], First, the reaction was shown to be first order in both substrate and catalyst. Moreover, a Hammett... 

Sames and co-workers also demonstrated that rhodium(I) catalysts also facilitate a C-H arylation of indole at the C-2 position (Scheme 16). While not explicitly described in their paper, they infer that the pivolate ligand may be involved in an internal proton-transfer, and it seems likely that this is in line with a CMD type activation step reported by Fagnou and Echaverran [20, 21] (opinion of Gaunt and... 

Scheme 57 Trauner s application of direct C-H arylation in the synthesis of ( )-rhazinilam...

Trauner applied a C-H bond activation approach to the synthesis of rhazinilam [81]. The synthetic power of direct C-H arylation on nucleophilic heteroarenes was demonstrated through formation of the strained 9-membered ring using intramolecular coupling to an unactivated pyrrole (Scheme 57). 

Third and finally, a short comparison of rhodium-catalyzed and other arene C-H arylation methods highlighting some of the challenges to overcome in the development of improved arene arylation methods will be given. 

Scheme 13 General catalytic cycle for the C-H arylation of arenes through iV-heterocyclic carbene formation [97-104]...

Scheme 14 First-generation Rh-catalyzed C-H arylation of heterocycles by Lewis et al. [102].

Scheme 25 Rh-catalyzed decarbonylative directed C-H arylation of arenes by Zhao and Yu [118]...

Scheme 27 Rh-catalyzed C-H arylation of benzene by Proch and Kempe [119]...

Scheme 30 Rh-catalyzed tandem addition/directed C-H arylation with NaBPh4 by Ueura et al. [123]...

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