Electron-rich heteroarenes

Reissert compounds (l-acyl-l,2-dihydro-2-quinolinecarbonitriles) have been prepared on cross-linked polystyrene and C-alkylated in the presence of strong bases (Entry 8, Table 15.25). Treatment of polystyrene-bound C-alkylated Reissert compounds with KOH leads to the release of isoquinolines into solution (Entry 9, Table 15.25). The reaction of support-bound quinoline- and isoquinoline /Y-oxides with acy-lating agents followed by treatment with electron-rich heteroarenes and enamines has been used to prepare alkylated and arylated derivatives of these heterocycles (Entry 10, Table 15.25 see also Table 15.26). 

Electronic properties of the substrate often activated C-H bonds are targeted, for example, with electron rich heteroarenes electrophilic palladation is favored at the most nucleophilic position and relies on the inherent reactivity of the system. Similarly if a proton-transfer pathway is under operation, activation is favoured on the most acidic C-H bond. 

Intermolecular direct arylations of heteroarenes with aryl halides were thus far predominantly accomplished with palladium or rhodium complexes [31, 39,75, 76], Hence rhodium catalysts proved applicable to various electron-rich heteroarenes. In contrast, less expensive and more versatile palladium catalysts allowed for direct arylations of both electron-rich and electron-deficient substrates. Generally, the problem of achieving regioselectivities in direct arylation reactions of heteroarenes is less pronounced than it is for simple arenes, since in many cases the heteroatom can be considered as an endocyclic directing group. 

Coupling reactions. Electron-rich heteroarenes (furan, thiophene, indole,...) couple with Arl using a catalyst derived from [Rh(CO)2Cl]2 and [(CF3)2CHO]3P and Ag2C03. ... 

After realizing that our hypotheses about oxidative cross-coupling reactions were not as unique as assumed, we quickly turned our attentirai to intermolecular oxidative amination reactions. In the carbazole example, regioselectivity was coti-trolled by the presence of a Lewis base that was attached near the C—H bmid that would be cleaved, resulting in a metallacyle intermediate. For die development of an intramolecular reaction, we chose to take advantage of the selectivity that is often observed in the selective metalation of electron-rich heteroarenes. At the time, the palladation of indoles was presumed to operate by an electrophilic aromatic substitution mechanism. (This has since been demonstrated to be incorrect, vide infra.) We hypothesized that regioselective palladation of an indole substrate could be followed by a subsequent C—N bond reductive elimination. At the time, the exact mechanism by which the intermediate containing Pd—C and Pd—N bonds could be formed was not clear, nor was the order of the two metalation steps, but the overall process seemed plausible. 

A visible light-mediated C—H difluoromethylation of electron-rich heteroarenes with PhS02CF2l was reported by Wang and co-workers... 

C—H borylation of indoles has been reported by a number of groups. Chirik and coworkers utilized pincer-ligated cobalt complexes with N-methyhndole and recorded the C-2 borylated indole (133) as the major product (2014JAC4133). The catalysts employed demonstrated high catalysis turnover and low catalytic loading and also demonstrated efficacy with other electron-rich heteroarenes (furan, thiophene, benzofuran) as well as electron-deficient pyridines. More recendy, platinum-NHC complexes have been used in the selective C—H borylation of indoles (2015JAC12211). The authors reported higher isolated yields with this... 

Regioselectivity for direct arylation of electron-rich heteroarenes ... 

C-H/C-X Coupling ofVarious Heteroarenes and Aryl Halides 17.2.4.1 Indoles and Pyrroles - Electron-Rich Heteroarenes... 

Scheme 11 Trifluoromethylation of electron-rich heteroarenes by photoredox catalysis...

Around the same time, the photocatalytic trifluoromethylation of electron-rich heteroarenes such as indole, furan, pyrrole, and thiophene using CF3I as the tri-fluoromethane source was reported by Cho and coworkers (Eq. (13.24)) [66b]. 

Compared to processes with electron-rich heteroarenes, the direct C-H arylation of electron-deficient Af-heteroarenes is often difficult. Recently, an efficient visible-light-induced arylation of electron-deficient Af-heteroarenes with aryl diazonium salts has been developed by Xue (Scheme 13.36) [72]. Using Ru(bpy)3Cl2 6H2O as photocatalyst, the reaction proceeds smoothly... 

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