Furan perfluoroalkylation

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)... 

Irradiation of cyclic ketones having perfluoroalkyl groups causes cleavage of a ring to yield acyclic products [I74 (equation 44) Similarly, perfluonnated ketones undergo decarbonylation when irradiated [775]. Gas-phase photolysis of perfluorodiazoketones, in the presence of a trapping agent, yields fluorinated furan as a major product [176] (equation 45)... 

The development of synthetic methods for the selective introduction of short-chain perfluoroalkyl groups into organic molecules is of interest in drug development [464]. Fluoromodifications often confer unique properties on a molecule, for example in terms of increased metabolic stability and lipophilicity and, as a consequence, the pharmacokinetic profiles are often improved [465]. Burger and coworkers developed a domino process consisting of a SN reaction combined with a Claisen and a Cope rearrangement which allows the transformation of simple fluorinated compounds into more complex molecules with fluoro atoms [466]. Treatment of furan 2-917 with 2-hydroxymethyl thiophene (2-918) in the presence... 

Pyrroles, furans, and thiophenes react preferentially with radicals at the 2-position. Thus, reaction of pyrrole with benzyl radicals gives 2-benzylpyrrole. In rather better yields, pyrrole and indole treated with per(poly)fluoroalkyl chlorides (RfCI) in the presence of sodium dithionite in DMSO produce 2-perfluoroalkyl products <2001JFC(111) 107>. Furans trap aryl radicals, generated from the Mn(OAc)3 oxidation of arylboronic acids <2003JOC578> or... 

Since perfluoroalkyl-substituted olefins and alkynes possess low-lying frontier orbitals, [4 + 2] cycloaddition reactions to oxazoles and thiazoles without strongly electron-donating substituents are unfavorable. On the other hand, five-membered heteroaromatic compounds possessing an electron-rich diene substructure, like furans, thiophenes, and pyrroles, should be able to add perfluoroalkyl-substituted olefins as well as alkynes in a normal Diels-Alder process. A reaction sequence consisting of a Diels-Alder reaction with perfluoroalkyl-substituted alkynes as dienophile, and a subsequent retro-Diels-Alder process of the cycloadduct initially formed, represents a preparatively valuable method for regioselective introduction of perfluoroalkyl groups into five-membered heteroaromatic systems. 

Perfluoroalkyl-substituted propynoates and furans react to give Diels-Alder adducts. The success of the subsequent retro process depends on the substitution pattern of the furan ring system. The adducts of unsubstituted furan are thermally relatively stabile, whereas the [4 + 2] cycloadducts of 2,5-dimethylfuran readily undergo a thermally induced retro-Diels-Alder reaction to give the 3-trifluoromethylfuran in high yield [91JFC(53)285] (Scheme 89). 

D. The calculations confirm that the negative end of the dipole is towards phosphorus. - The calculated dipole moments of phosphole (1.9 D) and pyrrole (2.0 D) are similar, and, unlike furan, the positive ends of the dipoles are towards the heteroatoms. Dipole moments have been used, in combination with results from other methods of study, to estimate the preferred conformations of the dichloride (179), of the phosphites (180), and of triarylphosphine oxides. The use of dipole moments to aid stereochemical studies of compounds has been reviewed. Additive polarizability parameters should not be used in the calculations, and it has been recommended that data should be obtained from model compounds containing identical environments for the phosphorus atoms. The sensitivity of bond moments to structural changes has been studied perfluoroalkyl groups lower the phosphoryl bond moment, and the P—N bond moment is very sensitive to the valence state of the phosphorus atom. The conformational analyses of phospho-nates, phosphonamides, silyl phosphates, and a number of dioxaphosphori-nans (181) - have been reported. The P—Se bond moment has been estimated to be 1.24 D. The zwitterionic structure (182) was identified by its high dipole... 

Perfluoroalkyl-Furan Derivatives The most common methods of synthesis of these compounds is perfluoroalkylation of furans, carried out using either radical, or ionic reactions. For example, the photolysis of... 

The only example of the cationic perfluoroalkylation of furan by trifluoromethyl cation (generated by radiolysis of CF4) resulted in a mixture of 2- and 3-substituted... 

The methods of synthesis for bis(perfluoroalkyl)furans are more developed. For example, 2-methyl-3,4-bis(trifluoromethyl)furan can be synthesized by the reaction of 2-methyl-furan-3,4-dicarboxylic with sulfur tetrafluoride. However, the main synthetic methods rely on the use of unsaturated fluorine-containing acyclic compounds. So, 3-trifluoromethylfurans 57 were prepared from p,p-bis(trifluoro-methyl)a,p-unsaturated ketones and tin(II) chloride. ... 

Perfluoroalkyl-1 -fluoroalkeny 1 phosphates undergo sequence of transformations involving the dephosphorylation and fluoride ion catalyzed cyclocondensation to give 3,4-diperfluoroalkylated furans 58. ... 

Furan Derivatives, Containing Three or Four Fluorine Atoms or Perfluoroalkyl Substituents Only a few furan derivatives with the named combination of substituents are known. 

The highest yields of 2-perfluoroalkylthiophenes were obtained when bis(per-fluoroalkanoyl)peroxides were used as the source of perfluoroalkyl radicals. Mechanistically reactions with thiophenes (similarly to furans) are considered to be initiated by one-electron transfers from the substrates to peroxide. 

Similar to furan, thiophene can be perfluoroalkylated in position 2 by the radicals, generated from perfluoroalkane sulfonyl chloride by ruthenium (11) catalyst. ... 

Owing to their relatively low thermal stability, perfluoroacylperoxides [RpC(0)0]2 undergo thermal decomposition generating perfluoroalkyl radicals. Although [RpC(0)0]2 were successfully used for the perfluoroalkylation furane, thiophene, and pyrrole, the reaction of perfluoroacylperoxides with pyridine does not result in perfluoroalkylation, due to side reactions caused by interaction of the peroxides with a lone electron pair of nitrogen. Sterically hindered pyridines, however, were reported to give perfluoroalkylated products. For example, compound 1 reacts with peroxide 2 giving isomeric pyridines 3 and 4 in low yield (Fig. 7.1). ... 

Other systems for generation of electrophilic perfluoroalkyl radicals were also applied to the synthesis of perfluoroalkylfurans. Thus, trifluoromethylation of furan and benzofuran with trifluoromethyl iodide in DMSO afforded the 2-trifluoromethyl derivatives in 16 and 30 % yield correspondingly [51], Better results were reported for the photocatalytic Ru(bpy)3Cl2-TMEDA system. Trifluoromethylation of... 

Perfluorinated heterocycHc compounds are of interest due to their synthetic uses and bioactivity. Bouillon and coworkers transformed fluori-nated fiirans into substituted pyrroles and 3-pyrrolin-2-ones (2004S711). 2-Perfluoroalkyl furans were treated with benzylamine in ether at room temperature for 16 h to provide a mixture of N-benzyl-3-pyrrohn-2-one diastereomers. 

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