Difluondes

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

In other work Rozen added molecular fluorine to a steroidal ene-one dissolved in ethanol at low temperatures to produce a vicinal difluonde in a cleaner, better yield reaction than previously obtainable [55] Although the reaction was not general, the stereoselectivity was very high, and contrary to addition of other halogens, addition was r>ii, characteristic of an electrophilic addition pathway... 

The tnmethylsilyl enol ether of 1 mdanone (3 2 mmol) in 2 mL of methylene chlonde is added to a mixture of xenon difluonde (4 mmol) and a catalytic amount of pyndimum poly (hydrogen fluonde) m 5 mL of methylene chlonde The mixture IS stured at 0 C for 2 h and poured into dilute sodium bicarbonate solution, tlie organic layer is separated and dned After concentration and column chromatogra phy (silica gel, hexanes), 2-fluoro-1 -mdanone (mp, 59 C) is obtamed in 87% yield... 

Substituted aryl hydrazones can be converted to geminal difluondes in satis factory yields by molecular fluorine [H4, iodine fluoride [ 5], and N bromo-suc-cinimide-pyridinium polyhydrogen fluoride or A -bromosuccinimide-polyvi-nylpyridinium polyhvdrogen fluoride [5(5] (equation 21) (Table 6)... 

Direct perfluoroalkylatwn of electron poor aromatic and heterocyclic systems with perfluorocarboxylic acids is mediated by xenon difluonde [165] (equation 142)... 

In a different appheauon, the selective alcoholysis of methylphosphomc difluonde is promoted by the capture of fluonde ion by sihcon [8J] (equation 74)... 

Gemmal difluonnated aliphatics are presented in Table 8 [22, 56 71, 75, 76, 77] and Table 9 [71, 76 87, 88, 89], divided by degree of substitution at the F-C-F position The fewer examples m this category reflects tlie limited synthetic aeces-sibility to these compounds Like the monofluonnated aliphatics, many of these difluondes have been reported by Weigert [71] and can be synthesized from the corresponding aldehyde or ketone by tismg DAST... 

NMR signals for difluoromethylene moieties range from -85 to -111 ppm (excluding difluorocyclopropyls), with viunal 7jjp values similar to the primary cases More compbcated sphttmg patterns arise from diastereotopic fluorines when a chiral center IS present in the gemmal difluonde Diastereotopic fluonnes may differ in chemical... 

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