Pyrrole radical trifluoromethylation

Other electron-rich aromatic compounds can be employed as substrates. Pyrroles were trifluoromethylated regioselectively at the 2-position (ref. 27). Recently, the system trifluoromethyl iodide-zinc-sulfur dioxide in DMF at low temperature was used for the trifluoromethylation of aminonaphtalenes and aminoquinolines (ref. 28). Computational results support the mechanism in which the electrophilic trifluoromethyl radical intertact with the aromatic ring at the sites with the greatest electron density of the HOMO orbitals. 

Bis(perfluoroalkanoyl)peroxides were also appUed for radical trifluoromethylation of pyrrole 2b [34], Performing the reaction in freon 113 at -30 °C was found to be optimal for aU peroxides. In this way 2-CF3-pyrrole 38b was regioselectively synthesized in 72 % yield (Table 1, entry 7). Lower yields were obtained both at higher temperature and in diethyl ether as a solvent. 

The A -nitrososulfonamide 70 was shown to be a convenient reagent for radical trifluoromethylation. UV irradiation of lb with 70 in the presence of diacetyl as a sensitizer led to 38b in 51 % yield (Table 1, entry 8). Distinct advantage of this method is easy handling of the solid 70 instead of gaseous CF3I or of the quite unstable bis(perfluoro-aIkanoyl)peroxides. 70 is assessable from trifluoronitroso-methane 69 in a one-pot procedure [35]. Te(CF3)2 was also used as a trifluoromethyl radical source for trifluoromethylation. The reaction proceeded under UV irradiation and led to a 25 1 mixture of pyrroles lb and 2b (Table 1, entry 9) [36]. 

Trifluoromethylation of pyrrole (and indole and imidazole) occurs on irradiation of a mixture of the compound with difluorodiiodomethane, again via a SET mechanism involving fragmentation of the radical anion (Scheme 31). The presence of the CF3 group in the final products, 45 and 46, is a result either of secondary decomposition of the initially formed—but not isolated—difluoroiodomethyl derivatives, or of formation of the CF3 anion or radical in situ [94], Perfluoroalkyla-tion of pyrroles can also be achieved by an SrnI mechanism—by reaction with perfluoroalkyl iodides in the presence of magnesium or zinc [95]. Indole, on the other hand, gives a mixture of the seven possible alkylated derivatives when irradiated in the presence of ethyl chloroacetate [96],... 

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