Ketone enolates fluorination,

It is more reactive than perchloryl fluoride and therefore not without danger. It forms, for instance, a highly explosive product with pyridine. Like perchloryl fluoride it reacts with enol ethers, esters and enamines, but at lower temperature (—78°) to yield the fluorinated ketones as well as addition... 

In contrast, fluorinated ketones have been used as both nucleophilic and electrophilic reaction constituents The (Z)-lithium enolate of 1 fluoro 3,3-di-methylbutanone can be selectively prepared and undergoes highly diastereoselec-tive aldol condensations with aldehydes [7] (equation 8) (Table 4)... 

The fluorination of enolates of ketone, amide, or hydrazone bearing a chiral auxiliary (SAMP, Evans oxazolidine) with nonchiral fluorination reagent (A-fluoro sulfonimides, A-fluoropyridine) occurs with excellent diastereoselectivities. ... 

Fluorination of sulfonamides 147 and 148 takes place upon deprotonation with NaH and reaction with perchloryl fluoride, FCIO3, to give products 149 and 150 (Scheme 19) <2000JOC7583, 2000CPB1954>. The resulting A-fluorosultams 149 and 150 have been used for the asymmetric fluorination of aryl ketone enolates (vide infra). 

Conjugate addition reactions to the E-alkenoate proceeded fruitfully [293]. Remarkably, ketone enolates added to the alkenoate (Eq. 106) to afford the Michael adducts in the absence of the three fluorine atoms, the retro-Michael reaction dominates, because a ketone enolate is more stable that the ester enolate generated by the conjugate addition process therefore some special driving... 

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. 

Selective fluorination in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluorination of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of alpha-fluoro ketones, hfita-diketones, befa-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluoride ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluorination of pyndmes to give 2-fluoropyndines was shown to proceed through pyridine difluondes [50]... 

Hydration of highly fluorinated ketones has been referred to under Acetals above.5 2-Acetyl-l-methylpyridinium ion is 8% hydrated in water see Enolization below. 

Lithiated di- and monofluorinated enol carbamates 566844 847 and 567848 are fluorine-containing acyl anion equivalents, which allow the synthesis of a-fluorinated ketones. 

Highly fluorinated ketones show some unusual keto-enol phenomena [122]. Remarkably, the pair 8.25A and 8.25B in Figure 8.25 cannot be equilibrated by acid or base the enol 8.25A, for example, can be distilled from concentrated sulphuric acid. In the presence of base, aldol condensation occurs faster than equilibration. 

Fluorination of Ketone Enolates. (+)-lV-Fluoro-2,10-(3,3-dichlorocamphorsultam) (1) reacts with ketone enolates to give a-fluoro ketones. For example, reaction of the sodium enolate of propiophenone 2 gives a-fluoropropiophenone 3 in 41% isolated yield (eq 1). No enantioselectivity, however, is observed due to racemization of the product under the reaction conditions. When a tertiary substituted ketone such as a-methyltetralone (4) is employed, the desired a-fluorinated product (S)-(-)-S is obtained in 76% ee and 53% isolated yield (eq 2). In this reaction, (+)-l was found to be more reactive, affording higher yields and better enan-tioselectivities than its parent (-)-N-fluoro-2,10-camphorsultam i.e., 35% ee, < 5% yield. ... 

A -Fluoro-dihydrobenzo[l,2-i isothiazole is an efficient agent for electrophilic asymmetric fluorination of enolates <1999JOG5708>. A -Fluoro-2,10-camphorsulfonamide 237 (see Section 4.05.6.4.2) is a good asymmetric reagent for a-fluorination of ketones <1998JOG9604>. 

Reaction with Enolates. TV-Fluorobenzenesulfonimide readily reacts with enolates to yield a-fluoro carbonyl compounds. Simple ketone enolates, prepared by treatment with hthlum his (trimethylsilyl)amide in THF at low temperature, are fluorinated by treatment with a molar equivalent of NFSi (eq 4). ... 

Fluorination of Enolates and Silyl Enol Ethers. iV-fluoro-Af-(phenylsulfonyl)henzenesulfonamide (1) can be used successfully to prepare a-fluorocarbonyl compounds starting from esters, ketones, or 8-dicarbonyl precursors by electrophilic fluorination of the corresponding enolates (eqs 1-3) or silyl enol ethers (eq 4). Diastereoselective fluorination of enolates with 1 has recently been reported. ... 

Fujita T, Sakoda K, Ikeda M, Hattori M, Ichikawa J (2013) Nucleophilic 5-endo-trig cyclization of 3,3-difluoroaflylic ketone enolates synthesis of 5-fluorinated 2-alkylidene-23-dihydioftiians. Synlett 24 57-60... 

The Behenna-Stoltz protocol was soon applied to a-fluoroketones. As shown in Scheme 5.26, the silyl enol ethers 80 of 2-fluoro-indanone, tetralone-, and ben-zosuberone can be reacted with allyl or methallyl carbonate to give the tertiary a-fluorinated ketones 81 in 83-95% ee [43]. The procedure that was also applied to an allylation of 4,4-dimethyl-6-fluorocyclohexenone offers an alternative to the enantioselective fluorination of enolates on the one hand and the decarboxylative allylation of fluorinated P-keto esters on the other hand vide infra). 

The stereodirecting effect of the iron complex can also be exploited for diastereo-selective fluorination and oxygenation of adjacent silyl enol ethers (Scheme 4-95). Transformation of the allyliron complex into the diene complex and subsequent removal of the complex moiety by oxidation with ceric ammonium nitrate provide the enantiopure a-hydroxylated or fluorinated ketone, respectively. ... 

In 2000, Solladie-Cavallo synthesized fluorinated ketones 408 from (+)-dihydrocarvone and investigated them in the asymmetric epoxidation of different fran -stilbenes and silyl enol ethers (Fig. 7.20) [285-287]. Later she reported rigid fran -decalones 409 which gave up to 70% ee (409a) and 20% ee (409b) in the epoxidation of ran -P-methylstyrene (Fig. 7.20) [288]. 

A -dien-3-ol ethers gives rise to 6-substituted A" -3-ketones. 6-Hydroxy-A" -3-ketones can be obtained also by autooxidation.Structural changes in the steroid molecule may strongly affect the stability of 3-alkyl-A -ethers. Thus 11 j5-hydroxyl and 9a-fluorine substituents greatly increase the lability of the enol ether/ while halogens at C-6 stabilize this system to autooxidation and acid hydrolysis. 

The enamines, enol ethers and enol acetates of A -3-keto steroids provide important substrates for fluorination with FCIO3. Reaction of such A -enol ethers and acetates (6) with perchloryl fluoride results in 6a- and 6jff-fluoro-A -3-ketones (7) and (8), the latter representing the more abundant isomer. Tetrahydrofuran or dioxane-water mixtures appear to be particu-... 

Annelation of enamines or enolates with fluorinated methyl vinyl ketones gives the corresponding cyclohexenones [116, 117] (equation 101)... 

Formal replacement of hydrogen by fluorine takes place in the a-position of a ketone by treatment of enol acetates with triethylamine tris(hydrogen fluoride).51-55 The kinetically favored isomers are formed.51,55 Furthermore, benzylic positions bonded with an electron-withdrawing group (ketone, ester, nitrile, sulfonate) can be fluorinated electrochemically.51" 6-58 There are also various examples of the preparation of a-fluorosulfides front sulfides.51... 

While fluoroxy compounds react well with enol derivatives, fluorine in general does not. However, there are various reports where such reactions are described and in certain cases even with decent yields. In 1982 it was reported that pyruvates with a dominant enolic form react well with fluorine, to give the corresponding fluoro derivatives l.78 Several silyl enol ethers 2 and 379 including ones made from 1,3-dicarbonyl derivatives 480 react quite satisfactorily with fluorine to give the expected a-fluoro ketones. Steroidal 16-enol acetates react with fluorine to form mainly 16a-fluoro-17-oxo steroids e.g. 5.81... 

Mixtures obtained in reactions of fluorine with acid salts were tested on ( )-stilbene and from one to six products were formed, e.g. formation of 25.12 Various enol acetates can be converted into a-fluoro ketones 26 in a similar manner.2-4... 

The reaction of potassium dienoxy borates with A-fluorobis(phenylsulfonyl)amine (la) gives y-fluoro enones in good yield. The potassium dienoxy borates are prepared by treating potassium enolates derived from unsaturated ketones with 2-phenyl-1,3,2-benzodioxaborole. This methodology offers a convenient alternative to the traditional fluorination of dienol acetates, ethers, or enamines.145 An example is given by the formation of 13.145... 

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