Gem-Difluoro compounds

Methyliodobenzene difluoride cleaves aryl dithioketals. The reactions are conducted in dichloromethane solutions at 0 °C to give gem-difluoro compounds in 65-90% yields [4 (equation 6)... 

Many aldehydes and ketones have been converted to gem-difluoro compounds with sulfur tetrafluoride SF4,240 including quinones, which give 1,1,4,4-tetrafluorocyclohexadiene derivatives. With ketones, yields can be raised and the reaction temperature lowered, by the addition of anhydrous HF.241 Carboxylic acids, acyl chlorides, and amides react with SF4 to give 1,1,1-trifluorides. In these cases the first product is the acyl fluoride, which then undergoes the gem-difluorination reaction ... 

Ketones are less reactive than the aldehydes (see Section 8.4.2.). Ketones, e.g. 1 and 3, can be converted to the corresponding gem-difluoro compounds, e.g. 2 and 4, respectively, with (dia-lkylamino)trifluoro-A4-sulfanes at temperatures ranging from 20 to 80 C (see Table 4). 

Suprisingly, the treatment of furanones such as benzofuran-3(2//)-one (6) with DAST does not result in the formation of the desired gem-difluoro compound, but instead in the formation of the monofluorinated addition product 7 in good yield.52... 

An excellent method for the preparation of gem-difluoro compounds from aldehydes and ketones consists of conversion of the carbonyl compound to the corresponding 1,3-dithiolane followed by treatment with two equivalents of l,3-dibromo-5,5-dimethylhydantoin (DBH) and pyridinium poly(hydrogen fluoride) (HF-pyridine) in methylene chloride. Attempted extension of this procedure to 7-methoxy-2,2-dimethyl-4-chromanone, however, gave only the dihydro- 1,4-dithiin derivative 1 in 78% yield. This transformation, which proceeded in excellent yield with a variety of 4-chromanones, was found to require only the DBH (i.e. fluoride ion played no role). 

The synthesis of gem-difluoro compounds 1 from aldehydes or ketones using sulfur tetrafluoride has already been discussed in Houbcn-Wcyl, Vol.5/3, p84 (see also VoI.ElOa, p336fi ). 

The reaction of aldehydes or ketones with organosulfur trifluorides yields gem-difluoro compounds... 

The reaction of hydrazones and their derivatives 1 with iodine monofluoride (IF), prepared from the elements, yields the corresponding gem-difluoro compounds 2 (Table 1). Unsubstituted hydrazones 1 (R = R = H) are usually the most suitable substrates for this transformation. 

Semicarbazones (Table 1, R = CONH2) also react with iodine monofluoride. The gem-difluoro compounds are generally obtained in lower yields than with unsubstituted hydrazones, but the corresponding aldehyde derivatives (entry 16) arc reactive in this case. Finally, in the reaction of tosylhydrazones, gew-difluorides are obtained in only low to moderate yields (entries 4 and 23). 

Other reagents, such as bromine monofluoride, generated in situ from A -bromosuccinimide and pyridinium poly(hydrogen fluoride) [NBS, (HF) /pyridine] or poly(4-vinylpyridinium) poly(hydrogen fluoride) [NBS, (HF) /PVP], and elemental fluorine, as well as electrochemical methods, have been described for the transformation of hydrazones into. gem-difluoro compounds. 

Yield of gem-difluoro compound in parentheses. Azine was obtained in 53% yield. 

Selenium tetrafluoride, which is a liquid at room temperature, reacts with aldehydes and ketones to form. gem-difluoro compounds in good yields (Table 3).96,9 The reaction is run under mild conditions in halogenated solvents or without solvent. 

A number of conversions of thiocarbonyl compounds into gem-difluoro compounds have been described in the literature, e.g. formation of 1.189 2,212 3,213-214 4,216 5,212 6,213 7 (Houben-Weyl. Vol.E4, p668),217 and 8.218 Since these reactions give difluoro compounds bearing heteroatoms in the a-position they are not discussed further here. Pyrolysis of 4 gives 1,1-difluoro-substituted alkenes in good yields.216... 

Table 12. gem-Difluoro Compounds from Dithioketals and (Difluoroiodo)arenes... 

The reaction of diazo compounds with an electrophilic fluorinating reagent, tri-fluoromethyl hypofluorite,22 has also been studied (Table 8, entries 9 13).19,20 The reactions are carried out at — 70 C using trichlorofluoromethane as solvent and mixtures of gem-difluoro compounds and fluoro(trifluoromethoxy) derivatives are obtained. Although conversion is generally complete, the yields of isolated products are low, due to their difficult separation.19 In some cases (entries 9, 11, and 12), ketones and epoxides arc formed as byproducts. Consequently, this method is not a useful alternative for the preparation ofgem-difluoro compounds. 

Portella, C., Brigaud, T., Lefebvre, O., Plantier-Royon, R. Convergent synthesis of fluoro and gem-difluoro compounds using (trifluoromethyl)trimethylsilane. J. Fluorine Chem. 2000,101, 193-198. 

N,N-DIFLUOROAMIDES Fluorooxytrifluoromethane. gem-DIFLUORO COMPOUNDS Molybdenium hexafluoride. 

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