Selective anodic fluorination reaction

Fuchigami and coworkers have developed conditions for highly selective anodic fluorination reactions of various heterocyclic compounds including sulfur-containing heterocycles, as discussed later [3,6]. 

Selective anodic fluorination reactions of aldehydes and cyclic ketones can be successfully carried in EtjN-SHF to give the corresponding acyl fluorides and fluoroacyl fluorides in good yields (Table 12, Scheme 31). In these reactions, fluoride salts such as EtjN 3HF... 

Early studies in electrofluorination were conducted by fluorination of chiral benzylic esters at a platinum anode in EtaN x 3HF/CH3CN moderate diastereomeric excesses up to 60% were recorded (Scheme 44.29). The diastereo-selective anodic fluorination of A -protected thiazolidines derived from L-cysteine or sulfides gave the corresponding fluoro derivatives in a Pummerer-type reaction mechanism in moderate yields and high to very high diastereoselectiv-ities, up to 99% (Scheme 44.30). ... 

Kirste A, Nieger M, Malkowsky IM, Stecker F, Fischer A, Waldvogel SR (2009) ortho-Selective phenol-coupling reaction by anodic treatment on boron-doped diamond electrode using fluorinated alcohols. Chem-Eur J 15 2273-2277... 

Generally, anodic benzylic substitution reactions take place readily. However, anodic benzylic fluorination does not always occur. The major competitive reaction is acet-amidation when MeCN is used as a solvent [24-26]. In contrast to these cases, triphenylmethane is selectively monofluorinated in 80% yield [27]. When Et4NF-/7HF n = 3,4,5) is used in the absence of MeCN, anodic fluorination of toluene and mono-fluoromethylbenzene provides mainly mono- and difluoromethylbenzenes, respectively [22]. On the other hand, difluoromethylbenzene affords only products fluorinated in the benzene ring [Eq. (4)] [28]. 

Anodic monofluorination of the side chain of various heterocyclic compounds has been systematically studied [82-84]. The active methylenethio group attached to heterocycles is selectively fluorinated to give the corresponding a-fluorinated products in moderate to good yields [Eqs. (36) and (37)] [82-87]. In these reactions, the choice of solvent and supporting fluoride salt is of great importance in order to achieve efficient fluorination reaction [84-87]. 

In contrast to the cathodic reduction of organic tellurium compounds, few studies on their anodic oxidation have been performed. No paper has reported on the electrolytic reactions of fluorinated tellurides up to date, which is probably due to the difficulty of the preparation of the partially fluorinated tellurides as starting material. Quite recently, Fuchigami et al. have investigated the anodic behavior of 2,2,2-trifluoroethyl and difluoroethyl phenyl tellurides (8 and 9) [54]. The telluride 8 does not undergo an anodic a-substitution, which is totally different to the eases of the corresponding sulfide and selenide. Even in the presence of fluoride ions, the anodic methoxylation does not take place at all. Instead, a selective difluorination occurs at the tellurium atom effectively to provide the hypervalent tellurium derivative in good yield as shown in Scheme 6.12. 

Laurent and coworkers found that anodic benzylic mono- and difluorination proceeds selectively when the benzylic position is substituted by electron-withdrawing groups (EWG) [Eq. (5)] [29,30]. In these cases, / -methoxy or />-chloro substituents on the benzene ring are necessary for the operation of efficient fluorination. In their absence, benzylic acetamidation becomes a major reaction. The use of sulfolane as a solvent instead of MeCN leads to higher yields of fluorinated products owing to the absence of competing acetamidation [31]. 

Suda and his co-workers reported anodic fluoro desilylation of P-trimethylsilyl-P-lactams as shown in Scheme 43. In this reaction, the selection of the trimethylsilyl as a good leaving group enables regioselectivity control in the fluorination process. 

Oxidation and reduction reactions in series of fluorinated pyrroles were also reported. Anodic oxidation of 5-fluoro-l-methyl-lH-pyrrole-2-carbonitrile 487 in acetonitrile in the presence of EtsN 3HF complex afforded 2,5,5-trifluoro-l-methyl-2,5-dihydro-lH-pyrrole-2-carbonitrile 488 with traces of 5,5-difluoro-l-methyl-lH-pyrrol-2(5H)-one 489. a-Methyl group in ethyl 4-fluoro-3,5-dimethyl-lH-pyrrole-2-carboxylate 44 can be selectively oxidized by Pb(OAc)4 in the presence of p-methyl group. The reaction led to a mixture of aldehyde 490 and acetate of the corresponding alcohol 491 in high total yield [23]. 

Another pioneering electrosynthesis was the soft fluorination developed by I.N. Rozhkov, I.L. Knunyants, etc. [64, 65]. Unlike the known hard fluorination in liquid HF [66], which leads to perfluorinated compounds, often accompanied by side reactions, the soft fluorination is a selective electrosynthesis. The process is performed on a Pt anode in MeCN at the oxidation potential of the substrate RH. The -eajv-e-p mechanism is suggested for this reaction [67-69] (Figs. 9.4 and 9.5) ... 

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