Fluoroalkylated aromatics

Other well-known reactions are those offluorinated olefins with fluoride ion and negatively substituted aromatic compounds leading to the formation of per-fluoroalkylated aromatic compounds The reaction may be considered an anionic version ot a Friedel Crafts process and can result m introduction of one or several perfluoroalkyl substituents [HI] Aromatic substrates include substituted and unsubstituted perfluorobenzenes [131, 212, 213, 214], fluorinated heterocycles [131, 203, 215, 216, 217, 218, 219, 220, 221, 222, 223], perchlonnated heterocycles [224] (equation 44), and other activated aromatic compounds [225] (equation 45) The fluorinated olefins can be linear or cyclic [208] (equation 46)... 

Synthesis of Fluoroalkyl Aromatics by Exchange of Activated Benzylic... 

Majority of known perfluoroalkylated aromatic heterocyclic compounds contain one or several nitrogen atom(s) in the aromatic ring. Examples of fluoroalkylated aromatic six-membered heterocycles containing atoms, such as phosphorous or antimony are extremely rare and this is the reason why this chapter is mostly limited to preparation and chemical transformations of nitrogen-cotitammg aromatic heterocycles, providing limited number of references to only few known examples of trifluoromethyl s-1,3,5,2,4,6-triazatriphosphinines. 

Konno T, Moriyasu K, Kinugawa R, Ishihara T. Rhodium-catalyzed [2 -I- 2 -I- 2] cycloaddition of various fluorine-containing aUcynes-novel synthesis of multi-substituted fluoroalkylated aromatic compounds. Org. Biomol Chem. 2010 8 1718-1724. 

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,... 

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)... 

Selectivity and reactivity of mixed anhydrides toward primary and secondary aliphatic and aromatic amines has been studied in details [42, 43] (equation 22) Fluorocarboxyhc acids and then denvahves are used as building blocks m condensa non reactions widi dmucleophihc species for the synthesis of fluoroalkyl-subshtuted lieteroaromahc systems [S 9, 40, 44, 45, 46, 47 4S] (equations 20 21, and 23)... 

In aromatic series, when hydrogen atoms are replaced by fluorine atoms or by fluoroalkyl groups, an enhancement of the log P occurs (Table 3) [13]. The CF3, CF3O and CF3S groups are the most hydrophobic substituents known. They are widely used in crop science [41]. 

Trifluoromethyl-3-amino-2-propanols are powerful (submicromolar) and reversible inhibitors of CEPT in human plasma. Reversibility of the inhibition seems to indicate that the inhibitor acts as a substrate analogue (Figure 7.64). Three important factors for the gain of affinity must be underlined (1) replacement of the propyl group by a trifluoromethyl (affinity 30x), (2) the R configuration at the hydroxyl (affinity 40x), and (3) the presence of a fluoroalkyl substituent on the third aromatic ring (affinity 40x)." ... 

The most reactive of the fluoroalkyl thioketones is hexafluorothioacetone which provides cycloadducts with numerous helerodienophiles, including butadiene and some aromatic compounds at low temperature. In the case of the aromatic compounds 2 1 cycloadducts are obtained (Table 6). ... 

In the presence of tris(dimcthylamino)sulfonium difluorotrimethylsilicatc64 65 as a source of nonhydrated fluoride ion.66 trimethyl(trifluoromethyl)si]anc undergoes perfluoroalkylation of polyfluoroaromatic compounds.64 Fluorinated aromatic substrates such as perfluoropyridinc, perfluorotoluene, perfluorobenzonitrile, and perfluorobiphcnyl can be fluoroalkylated, but se-lcctivities are difficult to control and some multiple substitution takes place, resulting in modest yields of monoadducts 8 in the 30-50% range.64... 

Dioxanes have been synthesized from l-O-allyl-l,2-diols by radical addition of per-fluoroalkyl iodides and subsequent nucleophilic cyclization.561 With sodium hydride, elimination occurs from iodides such as 1.3 other bases also give unsatisfactory results, whereas N-bromosuccinimide seems to be the reagent of choice for the cyclization to 1,4-dioxane 14. Similar results arc obtained with dibromodimethylhydantoin.561 Dihydrobenzofurans are synthesized by cyclodehydration utilizing the Vilsmeier reagent (chloromethylene)dimethylam-monium chloride is most practical.562 Nucleophilic aromatic substitution reactions with catechol derivatives also give the six-membered heterocycles.563 564 1.4-Dioxan-2-ones arc pre-... 

An interesting photochemical formation of different 1,4-dihydro-1,3,5-triazines (168-171) was demonstrated by Kobayashi et al.261 who irradiated substituted 1,3,5-triazines (167) of low aromaticity in pentane or cyclohexane, utilizing compounds with two different fluoroalkyl groups on the triazine ring. Two or three distinct products were isolated, the ratio of these dihydro compounds depending on the nature of both substituents and the solvent (which also serves as a reagent) [Eq. (82)].267... 

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