Ketones direct fluorination

Fluorination of ketones. Direct fluorination with reagent (1) often proceeds in... 

The impact of a carbonyl group on the chemical shift of a CF3 group somewhat emulates the effect of other electronegative substituents. As indicated by the examples of aldehyde and ketones in Scheme 5.28, when the carbonyl carbon is directly attached to the CF3 group, it causes shielding of the CF3 fluorines. Note that aryl trifluoromethyl ketones are considerably less shielded than are alkyl trifluoromethyl ketones. The fluorine signal of trifluoromethyl ketones of course always appears as a sharp singlet. The spectrum of l,l,l-trifluoromethyl-2-butanone, as... 

Ketones cannot be directly fluorinated by (difluoroiodo)arenes however, a-fluoroketones can be prepared by the reaction of silyl enol ethers with difluoroiodotoluene in the presence of BF3 OEt2 and the Et3N-HF complex [22], Some steroidal silyl enol ethers can be converted into the respective a-fluoroketones in a moderate yield [23]. 

Direct fluorination of aliphatics and non-C moieties Direct fluorination of benzenoid aromatics Direct fluorination of heterocyclic aromatics Oxidations of alcohols, diols and ketones with fluorine Photo-oxidation of a-terpinene and cyclopentadiene Oxidation of benzyl alcohol to benzaldehyde Homogeneously catalyzed oxidation of butyraldehyde Oxidation of sulfite to sulfate Photochlorination of aromatic isocyanates... 

The feasibility of isolating relatively stable salts of difluorosulfamic acid and their utility in performing difluoraminations of model ketones was demonstrated by Chapman et al. [130,131], offering the prospect of alleviating many of the problems inherent in the use of hazardous difluoramine (HNF2) in conventional difluoraminations. Sodium difluorosulfamate was prepared by direct fluorination of aqueous sodium sulfamate it could be isolated by separation from sodium fluoride by-product and water after neutralization and it could be safely stored cold. Difluoramination of 1,3-dibromoacetone by sodium difluorosulfamate in sulfuric acid (1% SO3) produced l,3-dibromo-2,2-bis(difluoramino)propane in 38% crude yield, comparable to conventional difluoramination. Later, Christe and coworkers [132] better characterized sodium difluorosulfamate (Raman and IR spectra) and other difluorosulfamate salts (X-ray crystallography). 

Wholly aromatic polymers are thought to be one of the more promising routes to high performance PEMs because of their availability, processability, wide variety of chemical compositions, and anticipated stability in the fuel cell environment. Specifically, poly(arylene ether) materials such as poly-(arylene ether ether ketone) (PEEK), poly(arylene ether sulfone), and their derivatives are the focus of many investigations, and the synthesis of these materials has been widely reported.This family of copolymers is attractive for use in PEMs because of their well-known oxidative and hydrolytic stability under harsh conditions and because many different chemical structures, including partially fluorinated materials, are possible, as shown in Figure 8. Introduction of active proton exchange sites to poly-(arylene ether) s has been accomplished by both a polymer postmodification approach and direct co-... 

On the way to fluorinated target molecules, a CF2 group may be also incorporated in the ketone framework in this case drastic conditions are required to promote the Reformatsky reaction with ethyl bromoacetate (lb). The example reported in equation 19 was carried out on 100 g scale and was directed to the synthesis of a fluoro analogue 23 of the anticancer drug chlorambucil94. 

Flexible aliphatic compounds are also selectively fluorinated. Such substrates may be alkanes, alcohols, carboxylic acid derivatives or ketones as long as the electron-withdrawing group is far enough from the reacting center (Table 2).44 There are differences in yields and reaction rates which are qualitatively easily understood and are directly related to the electron density of the reactive C —H bond. 

Directed introduction of fluorine has been developed on the basis of the above-mentioned observations. Ketones can be converted into ft-dioxo derivatives with ethyl formates. Thus, fluorination of enolates 12 gives the fluoro derivatives which readily decompose in the presence of potassium acetate to products 13 5 -fluorogriseofulvin (14),2 5 many fluorocyclohexanones.26 and 5-fluoro-4,4-dimethylcyclopent-2-enone (15)27 can be prepared in this way. 

Direct regioselective conversion of a variety of cyclic and acyclic ketones to a-fluoro ketones was achieved in high to excellent yield using NFTh (21) in acetonitrile solution.96 The collected results (Table 10) of this highly effective direct transformation show that a comprehensive range of ketones can be fluorinated a to the carbonyl group, without prior activation. 

Table 10. Direct a-Fluorination of Ketones Using l-Fluoro-4-hydroxy-l,4-dia-zoniabicyclo[2.2.2]octane Bis(tetrafluoroborate) (NFTh, 21)96...

Various chiral amines can catalyze the direct enantioselective a-fluorination of aldehydes. Enders and Hiittl have focused on the use of Selectfluor for the a-fluorination of aldehydes and ketones [24a], For the aldehydes, no enantiomeric excess was reported using L-proline as the catalyst. In an attempt to perform direct enantioselective a-fluorination of ketones, cyclohexanone was used as the model substrate and a number of chiral amines were tested for their enantioselective properties however, the enantiomeric excess was rather low and in the range of 0 to 36% ee. 

Enders D, Hilttl MRM (2005) Direct organocatalytic a-fluorination of aldehydes and ketones. Synlett 2005 991-993... 

First Direct Organocatalytic a-Fluorination of Aldehydes and Ketones... 

Functional groups containing the C = N bond, such as hydrazones, oximes and diazo compounds, can also be used in the synthesis of fluorinated derivatives and these reactions are the subject of this section. The reaction products in these procedures are usually the corresponding g cw-difluoromethylene compounds. Since oximes and hydrazones arc obtained from aldehydes and ketones, these reactions can be considered as an alternative to the direct transformation of a carbonyl group into the difluoromethylene group. As indicated in Section... 

Swelling resistance of fluoroelastomers is directly related to the fluorine content in the molecule. This is demonstrated by data in Table 5.3 [9]. For example, when the fluorine content is increased by mere 6% (from 65% to 71%), the volume swelling in benzene drops from 20% to 3%. Copolymers of VDF and HFP have excellent resistance to oils, fuels, and aliphatic and aromatic hydrocarbons, but they exhibit a relatively high swelling in low-molecular-weight esters, ketones, and amines, which is due to the presence of the VDF in their structure [10]. VDF-based fluoroelastomers... 

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