Double fluorination

T.B. Patrick, L. Zhang, Q. Li, Rearrangement and double fluorination in the deiodi-native fluorination of neopentyl iodide with xenon difluoride, J. Fluorine Chem. 102 (2000) 11-15. 

Stabilization of the lithium enolate by intramolecular chelation with fluorine of the C—F bond has been demonstrated by calculation. The (Z)-enolate (49) of fluoroacetaldehyde is more stable than the (E)-enolate (50) [24]. Likewise, the double fluorine-chelated (Z)-enolate (51) of 4,4,4-trifluorobutanal is the most stable among the lithium enolates (51-54) [25] (see Table 3.4). 

Due to its doubled fluorine atoms, polyvinylidenefluoride (PVDF), is even less affected by the environment than is PVF (including its property of fire retardance) and stands between PVF and the superior chemical properties of PTFE. However, PVDF has far better mechanical properties than PTFE. It is also used as a top coat to protect PVC coatings against environmental influences. 

Double Fluorination of Enolates. Double fluorination of monosubstltuted enolates is achieved selectively in a one-pot procedure by adding the starting carbonyl compound to 2.4-3.6 equiv of base inTHFat—78°C followed by the addition of 2.6-3.6 equiv of the Wfluorosultam, and warming up to room temperatures. For this process, KHMDS and potassium diisopropylamide are the bases of choice (eqs 7-9). ... 

Several cortisone derivatives with glucocorticoid effects are most active, if they contain fluorine in the 9or-position together with an Il(9-OH group. Both substituents are introduced by the cleavage of a 9,11 -epoxide with hydrogen fluoride. The regio- and stereoselective formation of the -epoxide is achieved by bromohydrination of a 9,11-double bond and subsequent alkali treatment (J. Fried, 1954). 

Particularly alkyl halides which have a perfluoroalkyl group at the /3-position undergo smooth carbonylation. Probably the coordination of fluorine to form a five-membered chelate ring accelerates the reaction. Double carbonylation to give the a-keto amide 915 is possible in Et NH with the fluorine-bearing alkyl iodide 914[769,770]. The ester 917 is obtained by the carbonylation of the /3-perfluoroalkyl iodide 916 in ethanol. 

It is also used ia the preparation of biologically active steroids where the fluorine is added in a cis configuration to the double bond (13,14). 

The limitations of this reagent are several. It caimot be used to replace a single unactivated halogen atom with the exception of the chloromethyl ether (eq. 5) to form difluoromethyl fluoromethyl ether [461 -63-2]. It also caimot be used to replace a halogen attached to a carbon—carbon double bond. Fluorination of functional group compounds, eg, esters, sulfides, ketones, acids, and aldehydes, produces decomposition products caused by scission of the carbon chains. 

Steric Factors. Initially, most of the coUisions of fluorine molecules with saturated or aromatic hydrocarbons occur at a hydrogen site or at a TT-bond (unsaturated) site. When coUision occurs at the TT-bond, the double bond disappears but the single bond remains because the energy released in initiation (eq. 4) is insufficient to fracture the carbon—carbon single bond. Once carbon—fluorine bonds have begun to form on the carbon skeleton of either an unsaturated or alkane system, the carbon skeleton is somewhat stericaUy protected by the sheath of fluorine atoms. Figure 2, which shows the crowded hehcal arrangement of fluorine around the carbon backbone of polytetrafluoroethylene (PTFE), is an example of an extreme case of steric protection of carbon—carbon bonds (29). 

Halogenation. Halogens add directly to the double bond of maleic anhydride to give dihalo succinic acids. However, different procedures are used for dihalomaleic anhydride derivatives. Fluorinated substrates offer access to difluoromaleic anhydride [669-78-3] (64). 

The principal use of antimony pentafluoride is as a fluorinating agent. It readily replaces all chlorines with fluorine in organic compounds, and it fluorinates double bonds and aromatic rings. 

Catalysis. Catalytic properties of the activated carbon surface are useful in both inorganic and organic synthesis. For example, the fumigant sulfuryl fluoride is made by reaction of sulfur dioxide with hydrogen fluoride and fluorine over activated carbon (114). Activated carbon also catalyzes the addition of halogens across a carbon—carbon double bond in the production of a variety of organic haUdes (85) and is used in the production of phosgene... 

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

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]... 

Perfluorinated organic bromides can be oxidatively fluonnated with elemental fluorine to derivatives containing tn- [124] and pentavalent [/25 126 127] bromine in yields up to 42% Perfluoroheptylbromine tetrafluoride has been used to fluonnate double bonds in halogenated alkenes [127]... 

Hydrogen fluoride adds to more complex molecules, such as unsaturated steroids, to give fluorinated derivatives [/, 8] Low temperatures and inert diluents, such as tetrahydrofuran or methylene chloride, are generally employed. With bicyclic unsaturated terpenes, rearrangements often accompany addition to the double bond [/]. 

Reactions of the halogen iluorides with other unsaturated functional groups are generally reported only with highly fluorinated substrates Hexafluorobenzene and denvatives [118] and octaflvoronaphthalene [119] react with mixtures of bromine and bromine trifluoride by 1,4 addition of fluorine followed by addition of bromine fluoride across a reniatning double bond (equation 22)... 

A number of reagents, including perfluoroalkylsulfur trifluorides [191] (equation 29), will add fluorine and sulfur to carbon-nitrogen double bonds [131]... 

The product from fluonnation of sodium acetate is acetyl hypofluorite [64], which IS isolated and characterized [65] The value of this reagent lies in its relative mildness, because it reacts cleanly with most olefins adding the elements of acetoxyl and fluorine [66] Tnfluoroacetyl hypofluorite adds cleanly only to benzylic or electron-rich double bonds... 

Up to 20 products with different numbers of fluorine atoms and double bonds have been isolated from the fluonnation of benzene with silver difluoride [d], manganese trifluoride [7], potassium tetrafluoroargentate [d], and potassium hexafluoronickelate [24] The composition of the products depends on the fluorinating agents and on the temperature (Table 1)... 

In quinoline and isoquinoline, the benzene ring is more receptive to fluorma-tion, its double bonds being saturated and the hydrogen atoms replaced in preference to those in the pyridine ring As with pyridine and its homologues, ring contraction takes place during fluorination with cesium tetrafluorocobaltate at... 

---