Pyridine perfluoroalkylation

A simple method for the generation of metal derivatives of perfluoroalkyl carbanions by the decarboxylation of alkali salts of perfluorocarboxylic acids, has also been used. For example, heating potassium perfluoroalkyl carboxylates in the presence of dipyridine disulfides in DMF or sulfolane leads to the formation of the corresponding pyridine perfluoroalkyl sulfides [61] (Scheme 28). 

Alkyl-5-arylisoxazoles (303) were prepared by the regiospecific reaction of appropriate 1,3-diketones (302) (R = alkyl or perfluoroalkyl) with hydroxylamine hydrochloride in pyridine (79MI41601). 

Direct perfluoroalkylation of heteroaromatics occurs with RFI when sodium hydroxymethane sulfinate (Rongalite) is present. 3-Perfluoroal-kylcoumarins can be obtained (90CC1781). The distribution of isomers from substituted pyridines is compatible with a radical reaction (90TL2711). 

Pyridines gave poor yields, whereas quinolines and pyrimidines were successfully perfluoroalkylated (91T6231). 

Cobalt trifluoride fluorination corresponds to the electron-transfer mechanism via a radical cation. RF groups attached to the ring enhance the stability of intermediate dienes and monoenes. Perfluoroalkyl pyridines, pyrazines, and pyrimidines were successfully fluorinated but pyridazines eliminated nitrogen. The lack of certain dienes was attributed to the difference in stability of FC=C and RFC=C and steric effects [81JCS(P1)2059]. 

These types of compounds can also be formed via a Wittig reaction [19]. Triphenylphosphine can be quatemized with a suitable alkyl iodide, and the resultant perfluoroalkylated phosphonium salt will react with aldehydes to give fluorinated alkenes which are easily hydrogenated (Scheme 3.4). This methodology has recently been expanded to the formation of perfluoroalkylated pyridines [20],... 

The exchange reaction of perfluoroalkyl iodides and iodopentafluorobenzene with dialkylzinc in the presence of Lewis base, such as diglyme or pyridine, afforded the corresponding bis(trifluoromethyl)zinc and bis(pentafluoro-phenyl)zinc in high yield [41] (Scheme 12). 

Alkyl and aryl thiols afforded with perfluoroalkyl iodonium salts in the presence of pyridine the corresponding sulphides in good to excellent yields [25], Several sulphides and sulphoxides upon reaction with trifluoroethyl phenyliodonium triflate were converted into 2,2,2-trifluoroethyl sulphonium salts [26]. 

Several amines such as anilines, pyridine, etc., were perfluoroalkylated affording the corresponding ammonium or pyridinium salts [26-28], Other substrates which underwent perfluoroalkylation included triphenylphosphine [26], sodium nitrite [29], potassium thiocyanate [29] and potassium selenocyanate [29]. 

The reaction of perfluoroalkylcopper compounds, prepared in situ from the perfluoroalkyl iodide and copper, with ip -hybridized organic halides [Eq. (73)] in refluxing pyridine utilizes the thermal stability of the intermediate copper compounds and their failure to react with sp -hybridized halides (29, 30). 

A Dewar isomer of unsubstituted pyridine was identified by Wilzbach, but it was very unstable.63 Other Dewar isomers of six-membered heterocycles, isolated and fairly stable, are substituted with perfluoroalkyl groups. However, 1,2-dihydroheterocyclic compounds such as a-pyrone or a-pyridone derivatives are easily photoisomerized to bicyclic Dewar isomers, which are useful for the synthesis of cyclobutadienes. The photochemistry of 1,2-dihydroheterocyclic compounds will be discussed, followed by those of fully aromatic compounds. 

The two examples just considered seem to suggest that the photoreaction of perfluoroalkylated pyridines would give the 1,4-bonded Dewar isomers. However, the photoreaction of 2,6-bis(heptafluoroisopropyl)-3,5-bis(penta-fluoroethyl)-4-trifluoromethylpyridine gave a product whose structure... 

These examples show that the 2,5-bonded Dewar pyridine can be formed even if it is substituted with perfluoroalkyl groups. In the second example in Scheme 38 another 2,5-bonded isomer was not formed. This fact shows that a steric effect is important. 

In 1977, the 2,5-bonded Dewar isomers of perfluoroalkylated pyridine were isolated by Chamber s group (145) 156). The photolysis was carried out in the gas phase. Therefore, thse isomers must be the primary products. Their distributions seems to be determined by the electronic interaction between the substituents on the double bonds and steric effects. 

FITS reagents reacted very easily with thiols in the presence of pyridine to give the perfluoroalkyl sulfides in good to high yields. S-perfluoroalkylation was selective in the case of polyfiinctional substrates. In the presence of groups such as hydroxy, carboxy, alkoxycarbonyl or dialkylamino, the sulfur atom was always selectively substituted.216 (Table 5.10)... 

Condensation of 2-acetyloxiranes with ethyl perfluoroalkanoates gives 2,3-dihydro-3-hydroxy-6-perfluoroalkyl-4//-pyran-4-ones, which on dehydration form 5-substituted 2-perfluoroalkyl-4//-pyran-4-ones (98T2819) (Scheme 31). The dehydration of hydroxy dihydropyranones intermediates was performed by the action of a slight excess of thionyl chloride in dry pyridine. 

The recent observation of COF2 and CF3S02F or PhS02Ph and PhCOPh in the reactions of TFMT with pyridine and phenyllithium98 supported the conclusion of exclusive S—O bond scission of perfluoroalkyl perfluoroalkanesulfonates by nucleophiles. 

J.C.S. Chem. Comm., 1975, 729, and R. D. Chambers, R. Middleton and R. P. Corbally, ibid., p. 731). Comment on these reports must await next year s review but it is pertinent to note here that the former report describes an example involving pyrylium cations in which the fate of all the ring carbons is defined while the latter describes transposition of perfluoroalkyl-pyridazines and -pyridines. 

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