Fluorination enol acetates

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-... 

Systems usually fluonnated by electropositive fluorine reagents include acti-vated alkenes (enol ethers, enol acetates, silyl enol ethers, and enamines), activated aromatic systems, certain slightly activated carbon-hydrogen bonds, and selected organometallics. 

Acyl hypofluorites react readily with ends, enol acetates, vinyl ethers, and enolates [39, 40, 41] (Table 2, entries 1-7) Steroidal enol acetates are also fluorinated smoothly [39] (equations 17-19)... 

Both the Af-fluorosulfonamides and the A -fluoroammonium salts are very effective in the fluormation of enol acetates, enamines, silyl enol ethers, and enolates (Table 2) The reactions are thought to proceed through a mechanism which involves Sf 2 attack on the fluorine atom, but contributions from electron-transfer pathways also exist [65, 68, 73, 75, 76, 79, 80, 81, 82]... 

Fluorination of an enamine, enol ether, or enol acetate with CF3OF gave 60-70% yields of fluoroketone (708). Bromination of an endiamine gave the bis-imonium salt (647). 

Attempts to use fluorine in the preparation of simple a-fluoro-carbonyl compounds were not successful initially. Even when derivatives of carbonyl compounds such as enol acetates were treated with fluorine, a complicated mixture of products was obtained from which none of the desired a-fluoro... 

Under similar conditions, the enol acetate and the trimethylsilyl ether of estrone were fluorinated to give the corresponding a-fluoro carbonyl compound (Fig. 54) [135]. 

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... 

F-Teda BF4 (6) is very effective for the fluorination of a wide variety of organic substrates steroidal enol acetates (Table 7)92 and silyl enol ethers, certain carbanions, mildly activated aromatic compounds, and sulfides bearing oc-H atoms.73,75,76,77,84,88 90 The products are obtained with good yields and regioselectivity under very mild reaction conditions (Table 8). 

Few attempts have been made to harness the electrophilic power of this reagent to fluorinate enol derivatives, but it seems that better results are obtained with other agents, as may be judged from Kobayashi and coworkers work where 2-fluorocholestenone was prepared from the enol acetate en route to the 2-fluorovitamin D311. An enol acetate on ring D also reacted to produce a 16-fluoroestrone (equation 182)246. 

Five research groups have investigated fluorination of enol acetates and silyl ethers with xenon difluoride, and mainly a-fluoroketones were formed22"24, 78-81. HF-catalyzed fluorination of cyclic enol acetates with xenon difluoride at room temperature gave a-fluorocycloalkanones, while the yield and contamination with cycloalkanones depend on... 

Scheme 8). For instance, the fluorination at the position a of ketones has been realized by the anodic oxidation of enol acetates (78) in an MeCN/Et3N-3HF/(Pt) system under potential control, giving a-fluoro ketone (79 equation 38). ... 

Fittorimted steroids. The action of fluoroxytrifluoromethane on the enol acetates of 3-keto-A4- and 3-keto-A Astcroids yields derivatives fluorinated at the 6- and 2-positions, respectively. ... 

Reactions of Enol Derivatives and Enamines.—Enolic acetates are transformed into fluoro-ketones by the action of fluoroxytrifluoromethane, a source of electrophilic fluorine (Scheme 10)/ Peroxylauric acid reacted with the enol... 

Trying to avoid too many hydrogens in sodium propionate we replaced die two in the a position with chlorine atoms. This time the reaction with fluorine at -75 °C resulted in a stable oxidizing solution. The low temperature F NMR spectrum revealed a sharp singlet at +134 ppm, a characteristic signal for the COOF fluorine nucleus. Also this oxidizer was reacted with the enol acetate of a-tetralone to give, in 85% yield, the... 

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