Aromatic perfluoroalkylation

Aromatic perfluoroaLkylation can be effected by fluorinated aUphatics via different techniques. One category features copper-assisted coupling of aryl hahdes with perfluoroalkyl iodides (eg, CF I) (111,112) or difluoromethane derivatives such as CF2Br2 (Burton s reagent) (113,114), as well as electrochemical trifluoromethylation using CF Br with a sacrificial copper anode (115). Extmsion of spacer groups attached to the fluoroalkyl moiety, eg,... 

Alkylated aromatic lubricants, phosphate esters, polyglycols, chlorotrifluoroethylene, siUcones, and siUcates are among other synthetics that came into production during much that same period (28,29). Polyphenyl ethers and perfluoroalkyl polyethers have followed as fluids with distinctive high temperature stabiUty. Although a range of these synthetic fluids find appHcations which employ their unique individual characteristics, total production of synthetics represent only on the order of 2% of the lubricant market. Poly(a-olefin)s, esters, polyglycols, and polybutenes represent the types of primary commercial interest. 

Other well-known reactions are those offluorinated olefins with fluoride ion and negatively substituted aromatic compounds leading to the formation of per-fiuoroalkylated aromatic compounds The reaction may be considered an amonic version of a Fnedel Crafts process and can result in introduction of one or several perfluoroalkyl substituents [/ /] Aromatic substrates include substituted and unsuhstiluled perfiuorobenzenes [J3l, 212, 213, 214], fiuorinated heterocycles [131, 203, 215, 216, 217, 218, 219, 220, 221, 222, 223],perchlorinated heterocycles [224] (equation 44), and other activated aromatic compounds [225] (equation 45) The fluonnated olefins can be linear or cyclic [208] (equation 46)... 

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)... 

Perfluoroalkylation of substituted benzenes and heterocyclic substrates has been accomplished through thermolysis of perfluoroalkyl iodides in the presence of the appropriate aromatic compound Isomeric mixtures are often obtained W-Methylpyrrole [143] and furan [148] yield only the a-substituted products (equation 128) Imidazoles are perfluoroalkylated under LTV irradiation [149] (equation 129). 4-Perfluoroalkylimidazoles are obtained regioselectively by SET reactions of an imidazole anion with fluoroalkyl iodides or bromides under mild conditions [150] (equation 130) (for the SET mechanism, see equation 57)... 

The reaction of perfluoroalkyl iodides with calcium amalgam at -20 to 40 °C has been used to prepare perfluoroalkyl carbinols in 30-70% yields [/, 2] Aromatic aldehydes (equation 1) and ketones (equation 2) undergo this reaction, aliphatic aldehydes give high boiling mixtures The results are interpreted in terms of the intermediate formation of an organocalcium species... 

Typical perfluoroalkylated aromatic derivatives prepared via this type of reaction are illustrated in Table 6. This methodology has been used for the preparation 5-(perfluoroalkyl)pyrimidines [194], heptafluoroisopropylated aromatics... 

Table 6, Perfluoroalkyl Aromatic Compounds Prepared via the Reaction of Perfluoroalkylcopper Reagents with lodo-or Bromoaromatic Compounds...

Perfluoroalkylation can be accomplished via direct reaction of peifluoroalkyl halides and copper with aromatic substrates [232, 233, 234, 235, 236] Thus, perfluoroalkyl iodides or bromides react with functionalized benzenes m DMSO m the presence of copper bronze to give the corresponding perfluoroalkylated products directly in moderate to good yields [233] (equation 157) Mixtures of ortho, meta, and para isomers are obtained [232, 233], The use of acetic anhydride as solvent gives similar results [234, 235], Similarly, the direct reaction of perfluoroalkyl iodides and pyrroles with copper metal regiospecifically gives the 2-perfluoroalkylpyrroles [236] (equation 158). 

FITS reagents), has undergone considerable development recently [141,142,143, 144, 14S. These compounds, available fromperfluoroalkyhodides (equation 76), are very effective electrophilicperfluoroalkylating agents They react with carban-lons, aromatic compounds, alkenes, alkynes, silyl enol ethers, and other nucleophiles under mild conditions to introduce the perfluoroalkyl moiety mto organic substrates (equation 77) (see the section on alkylation, page 446). 

Perfluocoalkyl groups thermodynamically destabilize double bonds and small rings, but they can kineiically stabilize highly stramed molecules [75]. This remarkable perfluoroalkyl effect has made possible the isolation of stmctures that are uncommon m hydrocarbon chemistry, especially valence-bond isomers of aromatics and heteroaromatics such as 1, 2, and 3 [108],... 

A model with overlapping perfluoroalkyl tail should be excluded, since in this case the difference A is independent of the length of the fluorinated chain. The calculations for the molecular form factor gives a reasonable agreement with the intensities of successive (OOn) harmonics for the model with overlapping aromatic parts of the molecules and the tilt (approximately 35°) of perfloro chains [41c]. This model also satisfies fhe requiremenfs for dense Ailing of space. The smecfic layers in fhe dimeric smecfic phase are well defined (cr = 2.5-3 A) and consisf of fwo sublayers of fhe fluorinafed and aromafic parfs of fhe molecules. 

Fig. 15. Tilt angles of the different molecular fragments as a function of temperature for polyphilic compound FsHnOCB aromatic core (circles), alkyl chain (crosses) and perfluoroalkyl chain (diamonds) (Ostrovskii et al. [45])...

The steric bulk of the perfluoroalkyl group can be demonstrated by examining crystal structures of suitable compounds. For example, the crystal structure of the para-substituted phenol clearly shows the size of the C6F13 group with respect to the aromatic ring (Figure 3.5). 

Cyclizations with perfluoroacylating agents seem to be quite general for the synthesis of 5(2i7)-oxazolones with aromatic substituents directly bonded to the heterocyclic ring. For example, perfluoroacylation of a solution of an arylgly-cine containing a phosphorus trihalide affords 4-aryl-2-(perfluoroalkyl)-5(2//)-oxazolones (Table 7.1, Fig. 12) Similar results were obtained when amino nitriles were used as starting materials. ... 

Supercritical CO, offers many advantages over conventional solvents for organic reactions. The challenge has been to find surfactants that will allow typical organic substrates to dissolve. Shu Kobayashi of the University of Tokyo has described (J. Org. Chem. 2004,69,680) the development of perfluoroalky) aromatics that serve well, as illustrated by the conversion of 10 to 11. Both the perfluoroalkyl aromatic and the Sc(OTf), are recovered at the end of the reaction. 

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... 

Aromatization of l-(perfluoroalkyl)-3,4-dihydroisoquinolines to the corresponding isoquinolines is accomplished by catalytic dehydrogenation using palladium on charcoal (Table 16).260... 

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