Indoles fluoroalkylated

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... 

Only 2-fluoroalkyl derivatives 573 were obtained when pyrrole and indole were treated with per(poly)fluoroalkyl chlorides (RpCl) in the presence of sodium dithionite in DMSO (Equation 137) <2001JEC(111)107>. 

Electro chemically reducible nitro- and cyanoarenes are used as mediators for SRN1 per-fluoroalkylation of heteroaromatics such asuracils (17) [15], purines (18), pyrimidines (19) [16], indoles (20), and imidazoles (21) [17] where the electroreductively generated arene anion radicals initiate the SET reaction [18] (Scheme 2.37). 

Knochel and coworkers discovered that phenylmagne-sium chloride transforms 2-nitrostilbenes to 2-aryIindoles (Scheme 2, equation 1) [6]. Hao s team reported a novel preparation of 2-fluoroalkyl indoles via the Grignard cyclization of Af-(2-bromoalkyl)phenyl imidoyl chlorides, which were prepared in two steps from the appropriate o-alkylaniline (eqnation 2) [7]. 

Akiyama et al. [33] were the first to introduce chiral phosphoric acids to the FCA reaction of nitroalkenes, and they found that the addition of 3-A molecular sieves dramatically improved both the reactivity and selectivity of the reaction between (3-nitrostryrene and indole (Scheme 9.13). A catalytic working model was proposed that phosphoric acid performed as a bifunctional catalyst to activate both indole and nitroalkene. This methodology was further extended to the reactions with pyrroles as nucleophiles [34] and fluoroalkylated nitroalkenes as electrophiles [35]. 

A convenient pathway to 2-fluoroalkyl-substituted indoles 114 was elaborated using the fluorinated A-[2-(haloalkyl)aryl]imidoyl chlorides 112 as key intermediates [45]. Treatment of the latter compounds with magnesium in tetrahydrofu-ran gave the Grignard compounds 113, which afforded the indoles 114 in high yields by intramolecular cyclization initiated by attack of the nucleophile on imidoyl fragment. 

The Friedel-Crafts fluoroalkylation of indoles (298) with fluoroalkylated nitroalkenes (299), catalysed by chiral phosphoric acid (300), has been described by Lin and Xiao (Scheme 78). ° ... 

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