Vicinal difluorides

Electrofluorination of carbon-carbon double bonds using the versatile Et3N- 3HF/CH3CN system [4] produces mixtures of cis-/trans-isomeric vicinal difluorides, often together, however, with products resulting from solvent incorporation. 

In the absence of an organic solvent, electrofluorination in neat Et3N 3HF of alkenes like styrene, stilbene, 2,3-dimethylbut-2-ene, or 2-methyl-2-butene yield the corresponding vicinal difluorides in 22 - 55 % yield. Butadiene produces a 1 2 mixture of 1,2- and 1,4- difluorides [5]. 

The technique has been developed to include the fluorination of vinyl sulphides to give vicinal difluorides in good yields [8]. 

Furthermore, the halofluorination method can also be modified to prepare vicinal difluorides by a one-pot two-step reaction. Halofluorination followed by nucleophilic halogen-fluorine exchange is carried out simply by adding silver(I) fluoride to a solution of the initially formed a-fluoro-/J-haloalkanes, effecting the exchange in situ202 203 (Table 12). 

Phenyl-substituted alkenes with halogen atoms at the double bond react with xenon difluoride in dichloromethane in the presence of hydrogen fluoride forming vicinal difluorides in 50% yield.35... 

Cycloalkenes treated with xenon difluoride in dichloromethane form vicinal difluorides in high yield with hydrogen fluoride catalysis. Indene produces difluorides in 72% yield the preferred <7 t/-isomer is formed.36... 

The hydrogen fluoride catalyzed fluorine addition to acenaphthylene and 1,2-dihydronaph-thalene by xenon difluoride results (predominantly via ami attack) in the formation of vicinal difluorides ( 70% yield).37 Phenyl-substituted cycloalkenes 5 (n = 1-3) form the appropriate difluorides the configuration being dependent on ring magnitude.38... 

Barton and co-workers have studied30 the reactions of trifluoromethyl hypofluorite with various alkenes and found that (Z)- and (T -stilbene give vicinal fluoro trifluoromclhoxy products and vicinal difluorides in chlorotrifluoromethane or diethyl ether, while vicinal fluoro methoxy adducts predominate when the reaction is carried out in methanol at —78 C. svn Addition predominates in all cases on the basis of the fluorination regioselectivity of many alkenes, the formation of a /1-fluoro carbcnium ion is proposed.30... 

The reaction of alkenes 2 in the presence of a nucleophilic species (hydrogen fluoride, methanol, acetic acid) gives vicinal difluorides, methoxy fluorides or acctoxy fluorides in high yield fluorine enters according to the Markovnikov rule.8... 

Treatment of epoxides with DAST results in the formation ofgem-difluorides, vicinal difluorides and bis(2-fluoroalkyl) ethers.54 The product distribution is dependent upon the nature of the epoxide. For example, cyclohexene oxide (1) gives a mixture of eis-difluorides and bis(a-fluoro) ethers, whilst styrene oxide (2) affords a mixture of difluorophenylethanes. This reaction is of little practical use due to the problems associated with the isolation of pure products. 

IV. Vicinal Difluorides / 451 Choice of reagents / 451 Experimental procedures / 453... 

In other work Rozen added molecular fluorine to a steroidal ene-one dissolved m ethanol at low temperatures to produce a vicinal difluoride in a cleaner, better yield reaction than previously obtainable [5S] Although the reaction was not general, the stereoselectivity was very high, and contrary to addition of other halogens, addition was syn, characteristic of an electrophilic addition pathway... 

Vicinal difluorides have been obtained on reaction of XeF2 with triphenylethylene, 9-benzylidenefluorene and tetraphenylethylene in CH2CI2 in the presence of HF at r.t. By contrast, no reaction was observed with CSSO4F 30 °C) unless MeOH had been added. In the latter case, Markovnikov-type fluoromethoxy adducts were isolated88. 

Acid-catalyzed liquid-phase fluorine addition with xenon difluoride to cis and trans 1-phenylpropene resulted in the formation of vicinal difluoride in high yield63. Photo-initiated reaction in methylene chloride at 0 °C also gave vicinal difluorides in a nonstereospecific manner, and a free-radical mechanism was suggested68. Unfortunately, this radical reaction does not appear to represent a general synthesis since reaction with 1-hexene, cyclohexene and 2,3-dimethyl-2-butene does not give vicinal difluoride products68. 

Diethylaminosulfur trifluoride gives results similar to those of the reaction of sulfur tetrafluoride with epoxides, but mixtures of geminal diduorides. vicinal difluorides and bis(2-lluoroalkyl) ethers are obtained in low to moderate yield, depending on the structure of the epoxide." ... 

Fluorine can also be added to alkenes by reaction with a solution of anhydrous hydrogen fluoride in pyridine (Olah s reagent) containing either Af-brotno- or A -iodosuccinimide, or iodine or bromine and silver nitrate. The final addition of silver fluoride to the reaetion mixture leads to the formation of vicinal difluorides 19,23.153... 

The reaction of styrenes with (difluoroiodo)arenes always leads to rearranged products, i.e. geminal rather than vicinal difluorides.1,1-Diphenylethene, for example, reacts with (difluoroiodo)benzene to yield 1,1-difluoro-1,2-diphenylethane (24), not the expected 1,2-difluoro-l,l-diphenylethane. Examples of reactions with (difluoroiodo)arenes are found in refs 109 and 156-159. 

The main byproducts in these reactions are usually vicinal difluorides. In this case the concerted fluorination involves a fluorine of the trifluoromethyl group in a six-membered ring. 

Anodic oxidation of olefins in the presence of fluoride ions provides mono- and/or difluorinated products [Eqs (2) and (7)] [10,33,34]. Butadiene gives a 1 2 mixture of 1,2-and 1,4-adducts [35]. Anodic fluorination of vinyl sulfides such as 2-(phenylthio)styrene provides vicinal difluorides [36]. 

Recently the feasibility of the addition of elemental fluorine to rather sensitive olefins has been demonstrated. The vicinal difluorides produced were predominantly cis. 

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