Silyl enols fluorination

Secondly, it possible to use the reagent Selectfluor to electrophilically fluorinate silyl enol ethers under very mild conditions.( ) We have used this route to access p-fluoro-a-keto esters 8 as intermediates to fluorinated dehydroamino esters 9 (Scheme 4) (20)... 

Selective fluonnation 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 fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

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. 

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]... 

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... 

Fluoropyridinium triflate (la) exhibits high selectivity in fluorinations. In a steroid 8 with two reaction sites, a conjugated and a nonconjugated vinyl acetate moiety, 1-fluoropyridinium triflate (la) reacts at the conjugated site only. On the other hand, steroid 9 with a silyl enol ether and a conjugated acetate moiety affords the product resulting from reaction at the former site only.44,52... 

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). 

F-Teda BF4 is effective for the selective addition of fluorine to steroids in good yield, re-gioselectively and, in many cases, stereoselectively at the 6- and 16-positions, under very mild reaction conditions (Table 7).92 Further, 6 will also efficiently fluorinate silyl and alkyl enolates, enamides, carbanions, a-alkenes and actived aromatic compounds (Table 8). As an extension of this method F-Teda BF+ has been used for the electrophilic fluorination of (fluorovinyl)tin compounds affording terminal fluoroalkenes (see Table 9).88... 

An enantioselective fluorination method with catalytic potential has not been realized until recently, when Takeuchi and Shibata and co-workers and the Cahard group independently demonstrated that asymmetric organocatalysis might be a suitable tool for catalytic enantioselective construction of C-F bonds [78-80]. This agent-controlled enantioselective fluorination concept, which requires the use of silyl enol ethers, 63, or active esters, e.g. 65, as starting material, is shown in Scheme 3.25. Cinchona alkaloids were found to be useful, re-usable organocata-lysts, although stoichiometric amounts were required. 

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... 

An alternative approach to an a-fluoro ketone is to convert the parent ketone into the corresponding silyl enol ether which is then fluorinated. 

Ruzziconi and coworkers used the ceric ammonium nitrate promoted C—C forming reaction to prepare polycyclic homo- and heteroaromatics starting from aryl-substituted silyl enolates and, more recently, the same strategy has been applied to the preparation of fluorinated naphthaldehydes and naphthyl ketones . 

Fluorination. These reagents are easy to handle and they readily find applications in fluorinating a great variety of compounds including phenols, silyl enol ethers, and 1,3-dicarbonyl compounds. 

This group continuously enlarged the scope of substrate to allylsilane, silyl enol ether 113 and oxindoles 115 for enantioselective catalytic a-fluorination (Scheme 6.34) [62]. They employed N-fluorobenzenesulfonimide (NFSI) as a fluorinating reagent with bis-cinchona alkaloid catalysts and excess base to provide the corresponding fluorinated compounds 114,115 in excellent enantioselectivities up to 95% ee. 

Cahard and coworkers prepared polystyrene-bound cinchona alkaloids (PS-CA, 119), and successfully applied to enantioselective a-fluorination of silyl enol ether 117. Soluble-phase PS-CA along with Selectfluor gave both good chemical and optical yields. Facile recovery of the PS-CA by solid/liquid separation allowed an... 

Scheme 2.93 Enantioselective electrophilic fluorination of silyl enol ethers by N-fluorodihydro-quinine 4-chlorobenzoate. The enantioselective fluorination reagent is generated in situ from F-TEDA-BF4 (Selectfluor) and dihydroquinine 4-chlorobenzoate [206].

Some nucleophiles add to iV-fluoro-pyridinium salts to give dihydropyridines in which elimination of fluoride occurs in situ to give the 2-substimted pyridine. However, the preparation of the pyridinium salts requires the use of elemental fluorine (31.1) and also, some carbanions are subject to competitive reactions such as C-fluorination. However, silyl enol ethers do react efficiently stabilised heteronucleophiles (phenolate, azide) can also be used, and isonitriles produce picolinamides. ... 

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