Xenon difluoride with aromatics

The results given in both Table 1 and in the reviews [4, 5 7, 8, I0 show that xenon difluoride reacts with a wide variety of aromatic substrates to produce regioselecuvely monofluorinated aromatics An example is the preparation of 6-fluoro-L DOPA [83] (equation 48)... 

Carboxylic acids react with xenon difluoride to produce unstable xenon esters The esters decarboxylate to produce free radical intermediates, which undergo fluonnation or reaction with the solvent system Thus aliphatic acids decarboxylate to produce mainly fluoroalkanes or products from abstraction of hydrogen from the solvent Perfluoro acids decarboxylate in the presence of aromatic substrates to give perfluoroalkyl aromatics Aromatic and vinylic acids do not decarboxylate [91] (equation 51)... 

Pyridine is converted into perfluoropiperidine (82) in low yield by reaction with fluorine in the presence of cobalt trifluoride (50JCS1966) quinoline affords (83) under similar conditions (56JCS783). Perfluoropiperidine can be obtained electrochemically. This is useful, as it may be readily aromatized to perfluoropyridine by passing it over iron or nickel at ca. 600 °C (74HC(14-S2)407). Recently, pyridine has been treated with xenon difluoride to yield 2-fluoropyridine (35%), 3-fluoropyridine (20%) and 2,6-difluoropyridine (11%), but it is not likely that this is simply an electrophilic substitution reaction (76MI20500). 

Extensive work on the interaction of aromatic compounds with xenon difluoride has been carried out in order to investigate the reaction mechanism and the scope of the fluorination depending on the substituents electronic nature.26-59 62 It has been found that benzene and substituted aromatics react with xenon difluoride at room temperature in the presence of hydrogen fluoride to form the typical products of electrophilic fluorination contaminated with low quantities of difluoro-substituted molecules. 

Perfluoroalkanccarboxylic acids react with xenon difluoride to form corresponding unstable fluoroxenon esters, which decompose to give perfluoroalkyl radicals successfully trapped by various substrates. Treatment of benzene in dichloromethane with a modest excess of tri-fluoroacetic acid and xenon difluoride at room temperature gives trifluoromethylbenzene in 33-42% yield. The better yields are achieved with aromatics bearing electron-withdrawing substituents.8x86... 

Difluorotri(phenyl)-/.5-stibane, the most readily accessible among the aromatic anti-mony(V) fluorides, can be synthesized by several alternate methods in addition to those described above, i.e. by substitution of fluorine for chlorine in dichlorotri(phenyl)-/i5-stibane with potassium fluoride109 or hydrogen fluoride,110 and by oxidative fluorination of triphenylstibane with fluorine (in chloroform),111 perfluoro-l-fluoropiperidine,112 (difluoroiodo)ben-zene,107 or xenon difluoride.10 1... 

Fhiorination of aromatics. The reagent reacts with toluene to form benzyl fluoride as the major product ( 65% yield). It is also useful for fluorination of phenols- and of alkyl ethers of phenols the or/Ao-isomcr is formed as the major product. Reactions with this reagent thus differ from those with xenon difluoride, which generally favors formation of paro-isomers. 

Liquid-phase fluorination of alkyl-substituted anisole derivatives with xenon difluoride depends strongly on the structure of the aromatic molecule. Substitution and addition processes were observed in the case of the methyl derivative, while beside substitution of the hydrogen atom, dealkylation was also established with l-methoxy-4-J-butyl benzene89,90 (Scheme 29). 

The fluorination of 2-bromo-4,5-dimethylphenol with xenon difluoride has again confirmed the strong dependence of the course of reaction on the aromatic structure, and substitution, addition, rearrangement and oxidation processes were in competition91 (Scheme 31). 

The substitution of hydrogen atoms by fluorine in aromatic compounds has been investigated with many classes of reagent, including elemental fluorine. hypofluorites, " fluoroxysulfates. xenon difluoride," and N-F reagents. " ... 

The fluorination of aromatic compounds with xenon difluoride has been extensively investigated. The fluorination of benzene with xenon difluoride in the presence of hydrogen fluoride as a catalyst results in the formation of fluorobenzene in 68% yield. Monosub-stituted aromatic systems are reported to give high yields of monofluorinated compounds, the isomer distributions of which arc similar to those observed in electrophilic substitution (Table... 

One of the first reagents used for electrophilic fluorination ivas xenon difluoride (XeF2) [168], a solid which is easy to handle and which can be used in solvents which are relatively inert toward oxidation, for example acetonitrile and dichloromethane. The reactivity is mostly determined by its strong oxidizing power, rendering its mode of action more oxidative than electrophilic fluorination. With XeF2 not only are typical electrophilic fluorinations of aromatic compounds possible but also the Hunsdiecker-like fluorodecarboxylation of carboxylic acids and fluori-native rearrangements of carbonyl compounds to difluoromethyl ethers [169-171] (Scheme 2.76.). 

Fluorination Fluorination of arylalkenes with xenon difluoride is enhanced by Sip4. The reagent combination also transforms aromatic aldehydes into difluoromethox-yarenes. 

Fluorination of aromatics by XeF2 in the presence of HF is thought, contrary to earlier belief, not to involve the aromatic cation radical. However, a cation radical is thought to accept fluoride ion in reactions of XcF2 with easily oxidized aromatics (anisole) in the absence of HF (Anand etal., 1975). In this connection zinc tetraphenylporphyrin has been oxidized to its cation radical with xenon difluoride (Forman et al., 1971) although fluorine hyperfine splitting was found in the esr spectrum, reaction with fluoride ion did not occur. 

Tanahe, Y Matsuo, N. Ohno, N. Direct perfluoroalkylation including trifluoromethy-lation of aromatics with perfluoro carboxylic acids mediated hy xenon difluoride. J. Org. Chem. 1988, 53, 4582-A-585. 

Radical-cations may also be involved in the formation of phenyl esters from aromatic carboxylic acids and benzene in the presence of xenon difluoride, and can apparently be detected by e.s.r. spectroscopy during the reaction of iViV-dimethylaniline with perfluoropiperidine. The last reagent gives a low yield of o- and p-fluorophenol in the ratio 3.5 1 in its reaction with sodium phenoxide, and the predominance of ortho substitution is ascribed to a cage mechanism of the type shown in (3). However, towards 2,4,6-tri-t-butylphenoxyl radicals the piperidine acts as a source of fluorine atoms to give the dienone (4). ... 

Xenon difluoride has been used to initiate oxidative decarboxylation of perfluorocarboxylic acids for Rp generation and with aromatic and heterocyclic compounds the perfluoroalkyl groups can also become incorporated into the aromatic ring [59]. On the other hand, Sipyagin et al. [60] have employed this method for the perfluoroalkylation of thiols such as polychloropyridine thiols. Two different methods were used the action of preformed xenon carboxylates or treatment of a pyridinethiol solution in RpCOOH directly with xenon difluoride. A range of isomeric perfluoroalkyl sulfides was obtained (Scheme 27). 

Tanabe Y, Matsuo N, Ohno N (1988) Direct perfluoroalkylation including trifluoromethylation of aromatics with perfluoro carboxylic acids mediated by xenon difluoride. J Oig Chem 53 4582-4585. doi 10.1021/jo00254a033... 

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