Addition of fluorine to double bonds

Addition of fluorine to double bonds preparation of 3 -chloro-5, 6a-difluoro-5o -cholestane by addition of fluorine, 453... 

In the case of addition of fluorine to double bonds (Table II), note that the corresponding initiation step (lb) is probably exothermic by 5-36 kcal and thus plays an important role. A second important possibility is the concerted reaction mechanism 2, which is exothermic by 50-68.4 kcal per carbon atom. 

Subsequently the work of R. F. Merritt clearly established the selectivity of additions of fluorine to double bonds in CFC13 at —78°C in preference to reactions with protons. Merritt and co-workers studied such unsaturated systems as indenes and acenapthenes (83), A4 cholestenone (84), 1,1-diphenyl-ethylene (85), Schiff s bases (86), and acetylenes (87). 

Of course, most reactive metal fluorides, such as cobalt trifluoride [268] and vanadium pentafluoride, will react with alkenes but the reactions can be very difficult to control, except for haloalkenes [269]. Much easier control is possible with xenon fluorides [137], the reactivity decreasing in the series XeFe > Xep4 > Xep2. Since the first report of the use of xenon difluoride for the addition of fluorine to double bonds, many studies have been published and reviewed [54, 135] (Figure 3.61). 

Under similar conditions selective addition of fluorine to double bonds, even with complex organic substrates such as steroids, can also be achieved [17] (Scheme 2.5). 

Addition of chlorine, bromine, and iodine to double bonds is a standard procedure in organic chemistry. Addition of fluorine to double bonds is used less often, as fluorine has a high tendency for radical reactions. However, a dilute stream of fluorine in nitrogen at low temperature and in polar solvents can suppress fluorine radical formation and encourage polar processes"2. The preferred syn addition of fluorine is opposite to the reaction of other halogens. 

Oxygen-containing Heterocycles Three-membered Rings. - The addition of oxygen to double bonds remains the most common method for epoxide synthesis, and several new variations on that theme have appeared this year. Thus, alkenes are converted into epoxides using a solution of elemental fluorine in an acetonitrile/water mixture with complete retention of olefin stereochemistry.1 Prat and Lett have re-examined the use of tungstic acid catalysed epoxidation in an attempt to define the scope and synthetic utility of the process. They have shown that reactivity increases with the nucleophilicity of the double bond and... 

Many different reagents are available that allow the addition of fluorine to a double bond as exemplified in equation 1 for the addition to cw-stibene [1, 2 3 4]... 

Fluorine is the most electrophilic halogen and only few examples of controlled addition of fluorine to carbon-carbon double bonds have been reported56 Milder reagents, such as XeF2, are generally used to form fluorine addition products. 

Reaction of 2-chloropyridine gives 2-chloro-6-fluoropyridine as the major product which arises from the preferential substitution of hydrogen over chlorine and would be unexpected on the basis of the nucleophilic substitution mechanism described above. The product obtained was suggested, therefore, to arise from the addition of fluorine to the most electron rich carbon-nitrogen double bond, followed by elimination of HF [155]. 

Merritt et al. [124,170-174] carried out some of the earliest additions of fluorine to carbon-carbon double bonds. The fluorination of cis and trans propenyl benzene in a nonpolar solvent at low temperature gave predominantly erythro and threo difluorides respectively. More recently, Rozen [175] carried out similar reactions, but used a more polar solvent (trichlorofluoro methane, chloroform and ethanol) and a very low concentration of fluorine. Thus, in the fluorination of cis and trans 3-hexene- l-ol acetate (Fig. 72), syn addition occured to give exclusively the erythro and threo difluoro compounds respectively. Corresponding results were obtained in the addition of fluorine to other alkenes, including cyclic alkenes and cyclic enones. 

In the fluorination of alkenes with a terminal double bond, a significant amount of trifluoro compound was produced. This is believed to occur by the loss of H+ from the cationic intermediate followed by addition of fluorine to the resulting double bond (Fig. 74). 

The addition of fluorine is successfully executed on various deactivated 7t-centers as well. Fluorine was used to prepare perfluorocyclopentadiene and its anion 6 for the first time by addition of fluorine to perchlorocyclopentadiene followed by total dechlorination.68 Fluorine undergoes addition to enones 7,65 including dioxine derivatives 9,69 chloroenone 1070 and even to the very deactivated double bond in maleic anhydride (11) forming difluorosuccinic acids.71... 

B Experimental Procedures 1. Addition of Fluorine to the Double Bond... 

The number of reactions of addition of fluorine to the C=C double bond is not as large as that of addition of chlorine or bromine, and few examples of practical application of reactions of elemental fluorine are available. However, there is wide scope for development106 of these reactions for preparative purposes. 

The interaction of fluorine with an organic compound liberates a quantity of energy which is frequently of the order of magnitude of, or greater than, the energy which binds the carbon atoms in chains. It is estimated 63 that the addition of fluorine to a double bond liberates ldS calories per mole, whereas chlorine liberates only 30 calories. Careful control qf the temperature throughout the reacting masses is therefore essential. Even in the most favorable cases, much decomposition occurs and carbon tetrafluoride is frequently the main reaction product.62-6 ... 

Korytnyk and coworkers have shown that reactions of xenon difluoride with acetylated glycals in the presence of boron trifluoride are a convenient route for the synthesis of 1,2-difluoro sugars, while the addition of fluorine to the double bond occurred predominantly from the less hindered side and cis adducts were mainly formed75, 76. Stereoselective transformation of tri-O-acetyl-D-galactal with xenon difluoride at -20 to +5 °C, without a catalyst in CFC13, after hydrolysis, afforded 2-deoxy-2-fluoro-D-galactose in 63% yield77. 

Sodium methoxide is a catalyst for addition of alcohols across double bonds of fluorinated olefins. The reagent in this reaction is methoxide anion, which adds to the carbon of the double bond that has lower electron density. Because of a strong electron 7i-back-donation by fluorine, the lower electron density is at the carbon linked to two fluorines. 

This fluorination reaction is basically caused by the addition of fluorine to carbon double-bond and the displacement of hydrogen by fluorine according to the equation. 

Reaction of alkenes with an electrophilic fluorinating agent such as caesium fluoroxy-sulphate, in the presence of fluoride ion, can result in addition of fluorine to the double bond [264] (Figure 3.59). 

Addition of fluorine to carbon-carbon double bonds G G GFGF... 

Under ordinary conditions fluorine itself is too reactive to give simple addition it attacks other bonds and mixtures are obtained. However, F2 has been successfully added to certain double bonds in an inert solvent at low temperatures (—78°C), usually by diluting the F2 gas with Ar or Addition of fluorine has also been accomplished with other reagents (e.g., p-Tol—IF2/Et3N 5 HF) and a mixture of PbOa and SF4. ... 

---