Perfluoroalkyl carbanions

Perfluoroalkyl carbanions, generated by reversible nucleophilic addition of a fluoride anion to fluoroalkenes, react with dry benzenediazonium chloride in dimethyl formamide, giving phenylazoperfluoroalkanes in 41-53% yield (Dyatkin et al., 1972). The dianion obtained from 1,2-dinitrobenzene with dipotassium cyclo-octatetraenide reacts in a complex way with arenediazonium salts, forming 4-aryl-azo-2-nitrophenol in 46-58% yield (Todres et al., 1988). 

For medium-scale synthesis of fine chemicals and pharmaceuticals, especially, a variety of methods for nucleophilic perfluoroalkylation have assumed an important role. For nucleophilic perfluoroalkylation, either perfluoroalkyl carbanions, carba-nionoid , or perfluoroalkyl metal species must be generated, stabilized, and reacted with suitable electrophiles [33]. 

All perfluoroalkyl carbanions are stabilized by the negative inductive effect —If) of their fluoro substituents. At the same time, a-fluoro carbanions are destabilized by electronic p-tr repulsion of the lone electron pairs of the fluorine and at the anionic center (+f effect). This is reflected in the relatively weak acidity of CHF, in comparison with the other haloforms - the pfQ values of the various trihalo-methanes are CHF, 30.5, Cl ICI, 22.4, CHBr, 22.7, and Cl I, 68-70 [34]. 

I. L. Reactions of perfluoroalkyl carbanions with sulfur. Tetrahedron 1973, 29(18), 2759-2767. 

Further fragmentation of perfluoroalkyl carbanions was studied very thoroughly by Arsenault et al. [66], who found that the initial formation of the respective CmF2m+A ion is followed by fluorine atom migration and thus charge migration throughout the whole linear perfluoroalkyl chain (Fig. 4). They rationalize this... 

ONSH is an efficient tool for introduction of perfluoroalkyl groups into electron-deficient arenes. Due to moderate nucleophilicity and stability of perfluoroalkyl carbanions, the reaction proceeds only with highly electrophilic arenes such as azinium salts (Scheme 11.10) [20, 21]. 

A simple method for the generation of metal derivatives of perfluoroalkyl carbanions by the decarboxylation of alkali salts of perfluorocarboxylic acids, has also been used. For example, heating potassium perfluoroalkyl carboxylates in the presence of dipyridine disulfides in DMF or sulfolane leads to the formation of the corresponding pyridine perfluoroalkyl sulfides [61] (Scheme 28). 

Sodium nitrite in dimethylformamide acts as a nucleophile and reacts with perfluoropropene to generate a perfluoroalkyl nitrite anion The intermediate carbanion undergoes intramolecular nitrosation with loss of carbonyl difluoride to give tnfluoroacetic acid upon hydrolysis [5] (equation 6)... 

The haloform reaction of unsymmetrical perfluoroalkyl and co-hydroper-fluoroalkyl trifluororaethyl ketones gives the alkane corresponding to the longer alkyl chain [54] (equation 53) If the methyl group contains chlorine, the reaction can take different pathways, leading to loss of chlorine (equation 54), because of the variable stability of the chlorine-substituted methyl carbanions in alkali. 

The reactivities of the substrate and the nucleophilic reagent change vyhen fluorine atoms are introduced into their structures This perturbation becomes more impor tant when the number of atoms of this element increases A striking example is the reactivity of alkyl halides S l and mechanisms operate when few fluorine atoms are incorporated in the aliphatic chain, but perfluoroalkyl halides are usually resistant to these classical processes However, formal substitution at carbon can arise from other mecharasms For example nucleophilic attack at chlorine, bromine, or iodine (halogenophilic reaction, occurring either by a direct electron-pair transfer or by two successive one-electron transfers) gives carbanions These intermediates can then decompose to carbenes or olefins, which react further (see equations 15 and 47) Single-electron transfer (SET) from the nucleophile to the halide can produce intermediate radicals that react by an SrnI process (see equation 57) When these chain mechanisms can occur, they allow reactions that were previously unknown Perfluoroalkylation, which used to be very rare, can now be accomplished by new methods (see for example equations 48-56, 65-70, 79, 107-108, 110, 113-135, 138-141, and 145-146)... 

In this section the synthesis of fluoroalkyl (Section 15.1.4.1.3), a,a-difluoroalkyl (Section 15.1.4.2.3), and trifluoromethyl- and perfluoroalkyl ketones are discussed collectively. The second most widely used method for synthesizing peptide fluoromethyl ketones is the Henry nitro-aldol condensation reaction, which involves the use of (3-nitro alcohols to build the fluoromethyl ketones. As with the modified Dakin-West procedure, the Henry reaction has also been used to synthesize mono-, di-, tri-, and extended fluoromethyl ketones, making it another extremely versatile synthetic method.19 12 19 27 29 33 341 However, similar to the Dakin-West procedure, the products of the Henry reaction are not chiral, since an achiral carbanion is involved in the crucial carbon bond forming step. 

Photo-stimulated reactions of neopentyl iodide with several carbanionic nucleophiles have been studied in which inhibition experiments with the TEMPO radical trap suggest the reaction occurs via an SrnI mechanism.76 Comparison of 22 nucleophiles in then. Srn 1 reactions with iodobenzene by Fe(II)- and photo-induction has revealed that both are enhanced by high electron-donation ability of the nucleophile. The radical anion Phl is a key intermediate.77 The SET reactions of perfluoroalkyl iodides have been reviewed.78 Flash photolysis of H2O2 was used to generate HO and 0 radicals which were reacted with a, a. z-trifluorotolucnc (TFT) and 4-fluorotoluene (4FT) and the rate constants calculated.79 The diminished reactivity of TFT towards HO or O with respect to toluene or benzene was consistent with radical addition to the aromatic ring, whilst the reactivity of 4FT was of the same order as electron-deficient toluenes, which favour H abstraction from the aliphatic side-chain. 

Clearly, factors influencing electron-affinity of the fluorinated alkene, i.e. the influence of F or perfluoroalkyl (RP) as a substituent at the double-bond, are important to consider, as are the effects of these substituents on carbanion (3) stabilities. 

Phenylenediamine and 2-aminophenol initially give N-arylimidoyl fluoride. Elimination of hydrogen fluoride from the product and further intramolecular nucleophilic cyclization lead to perfluoroalkyl derivatives of benzimidazole and benzoxazole, respectively. In the case of 2-aminothio-phenol, the reaction occurs at the sulfur atom and forms a carbanion. If RF is fluorine, then the carbanion is destabilized by the interaction of the lone electron pairs of fluorine with the center, and the stabilization reactions occur with participation of the proton. If, however, RF is the trifluoro-methyl group, the negative charge is stabilized by it. The fluoride ion is eliminated with further intramolecular nucleophilic cyclization. 

These remarkable electrophilic reagents have been used to carry out perfluoroalkylation of various nucleophilic systems, including carbanions, activated aromatics and enolate derivatives examples are shown in Figure 5.11. 

The reason for this - at first glance - unexpected behavior is inversion of the electrostatic partial charges (compared, e. g., with the corresponding iodoalkanes) by the negative inductive effect of the perfluoroalkyl moiety. Nevertheless, in the presence of some classes of nucleophile, for example thiolates, resonance-stabilized carbanions, or enamines, the behavior of perfluoroalkyl halides is sometimes puz-... 

Resonance-stabilized carbanions, for example enamines [29], are good substrates for the SET-induced radical perfluoroalkylation (Scheme 2.104). 

Scheme 2.109 Principal methods for generation of fluorinated carbanions and perfluoroalkyl metal compounds (Rp = (per)fluoroalkyl, Arp = (per)fluoroaryl, M = metal, X = halogen, B = base, S = solvent). The particularly unstable trifluoromethyl anion can be stabilized by formation of an adduct with a suitable solvent, for example DMF, which itself acts as a CFj"" source in a haloform-like reaction (bottom).

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