Furans, 2-fluoro-3-trifluoromethyl

Perfluoro ketones and perfluoro a-diketones, with a trifluoromethyl group in the -position to the carbonyl, cyclize in the presence of antimony(V) fluoride to give furan derivatives, as reviewed by Krcspan and Petrov.4 Perfluoro(4-methylpentan-2-one) (1) rearranges to per-fluoro(2,4-dimethyltetrahydrofuran) (2) in 84% yield, when heated in the presence of anti-mony(V) fluoride.5... 

In perfluoro a-diketone 7, which lacks a trifluoromethyl group /i to the carbonyl in the 2-position. it is the carbonyl in the 3-position that participates in the cyclization to form per-fluoro(2-acctyltetrahydrofuran) (8), when 7 is heated at 150 C in the presence of antimony(V) fluoride.5 Perfluoro(2-methyltetrahydropyran-3-one) also rearranges to furan derivative 8 in high yield when heated at 100 C in the presence of antimony(V) fluoride for 20 hours.5... 

The [4+1] cycloadducts formed from 4,4-bis(trifluoromethyl)-l-oxa-buta-1,3-dienes (92JPR219) and tin(II )-chloride are transformed on heating into 4,4-difluoro-3-trifluoromethylbut-3-en-l-ones, which on treatment with sodium hydride yield 2-fluoro-3-trifluoromethylfurans (92CC348). When heated with phosphorus pentasulfide, l-aryl-4,4-difluoro-3-trifluor-omethylbut-3-en-l-ones give 2-fluoro-3-trifluoromethylthiophenes. The fluorine atom at C—2 of the furans and thiophenes can readily be substituted by a wide variety of nucleophiles (92JPR3II). This reaction sequence represents a preparatively useful method for the selective introduction of biologically relevant substituents into the C—2 position of 3-trifluoro-methyl-substituted furans and thiophenes (Scheme 87). 

The reactions of hexafluoroacetone with trimethylsilyl ethers of enols form 4,4-bis(trifluoromethyl)-l-oxabuta-l,3-dienes (92JPC311). When heated in the presence of tin(II) chloride, the latter are transformed into 4,4-difluoro-3-trifluo-romethylbut-3-en-l-one. Subsequent treatment with sodium hydride leads to 2-fluoro-3-trifluoromethylfuran, while with phosphorus pentasulfide the product is 2-fluoro-3-trifluoromethylthiophene (92JCS(CC)348). Partially fluorinated 1-oxopenta-1,4-diene, derived from hexafluoroacetone, is employed as an intermediate in the syntheses of fluorinated furans (92JCS(CC)349) and thiophenes (92JFC(58)380) (Scheme 9). 

The reactions of a-halo-substituted fluorine-containing furans with nucleophilic reagents ° ° are the most studied reactions proceeding with participation of halogen atoms. A fluorine atom in 2-fluoro-3-trifluoromethyl-5-aryl-furans 224 is replaced smoothly by various nucleophiles.The similar reactions were reported for 2-fluoro-3 -trifluoromethyl-5 -aryl-thiophenes. ... 

Heterocycles containing limited amount of fluorinated substituents (usually 1-3) can be named using trivial names or conventional nomenclature in combination with indication of the position of fluorinated substituents, for example, 2-fluoro-4-tri-fluoromethylpyridine. The situation becomes more complicated in case of poly-fluorinated and completely fluorinated heterocycles. In case of heterocycles with relatively small number of fluorinated substituents and well-defined stmctures, Greek or Latin numeral roots can be used. Names such as hexafluoropropene oxide, 2,2-bis (trifluoromethyl)oxirane, 2,2,3,3-tetrafluorooxetane, tetrakis(trifluoromethyl)furane, pentafluoropyridine, tetrafluoropyridazine, tetrafluoropyrimidine, and heptafluoro-quinoline are unambiguous and commonly accepted (see Fig. 0.1). 

The fluorine atom adjacent to a trifluoromethyl group in the furan ring shown below could be replaced under mild conditions by various nucleophiles. Consequently, the reaction of 2-fluoro-3-trifluoromethylfuran with allyl alcohol followed by a Claisen rearrangement led to the formation of trifluoromethyl substituted butenolides <01TL1657>. 

The section highlights synthesis of compounds demonstrated physiological activities using fluoro- or trifluoromethyl-substituted furans as starting compounds. Acylation of aniline 287 with 5-fluorofuran-2-carbonyl chloride gave amide 288 which inhibited c-jun A-terminal kinase at submicromolar level [162],... 

Buiger K, Helmreich B, Hennig L, Spengler J, Albericio F, Fuchs A (2007) Partially fluori-nated heterocycles from 4,4-bis(trifluoromethyl)-hetero-l, 3-dienes via C-F bond activation -synthesis of 2-fluoro-3-(trifluoromethyl)furans. Monatsh Chem 138 227-236... 

The PdCl2(CH3CN)2 proved to be a highly effective catalyst (5-10 mol %) in the cyclization-isomerization of trifluoromethyl-substituted a-hydroxy enynes, providing an efficient method to build fluoro-containing furans and 2//-p)rans. ... 

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