Indole perfluoroalkylation

Pyrroles, furans, and thiophenes react preferentially with radicals at the 2-position. Thus, reaction of pyrrole with benzyl radicals gives 2-benzylpyrrole. In rather better yields, pyrrole and indole treated with per(poly)fluoroalkyl chlorides (RfCI) in the presence of sodium dithionite in DMSO produce 2-perfluoroalkyl products <2001JFC(111) 107>. Furans trap aryl radicals, generated from the Mn(OAc)3 oxidation of arylboronic acids <2003JOC578> or... 

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],... 

The majority of published work on aza-ylides concerns their applications in synthesis, and here we report a selection of contributions from this area. The Staudinger reaction is a popular route to aza-ylides and has been used to prepare a series of perfluoroalkyl-tagged aza-Wittig reagents, e.g., (68), which were generated in situ (Scheme 22), and utilised in the synthesis of 3//-quinazolidine-4-ones in a fluorous biphasic system. A method for the preparation of aza-polycyclic compounds derived from pyrrolidine, indolizidine and indole has... 

There are few examples of radical substitution of benzofnran or benzothiophene perfluoroalkylation of benzofuran is one snch, as illnstrated. This process can also be applied to 2-snbstitution of thiophene, pyrrole, imidazole and indole. 

Figure 7.2 Perfluoroalkylation of indole using perfluoroacyl peroxide 2.

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