A-Fluoro carbonyl compounds

Many fluorinations by electropositive fluorine reagents produce a-fluoro carbonyl compounds as the final result An extensive review exists on the preparation of a-fiuorocarbonyl compounds [101 Also, electropositive reagents are used widely in the preparation of F-labeled radioactive materials required in positron etmssion tomography for biomedical research Excellent reviews are available on fluonne-18 labeling [//, 72]. 

For a review of the preparation of a-fluoro carbonyl compounds, see Rozen, S. Filler, R. Tetrahedron, 1985, 41, 1111. For a monograph, see German, L. Zemskov, S. New Fluorinating Agents in Organic Chemistry Springer NY, 1989. 

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]. 

Regretfully, there are few examples of fluorination by l-fluoropyridin-2(l//)-one (1), so it is difficult to evaluate its synthetic utility. This reagent has been used to obtain a-fluoro carbonyl compounds 4.28... 

Enol ethers can be regiospecifically fluorinated to form a-fluoro carbonyl compounds. In this way it is possible to synthesize fluorinated oxo steroids as the carbonyl groups not activated by the trimethylsilyl (or acetyl) enol ethers are not fluorinated.54... 

Preliminary fluorination experiments using optically active A -fluoro compounds ( —)-2b and ( + )-2c show that there is reaction with various metal enolates (Table 16) generated under standard reaction conditions to give the anticipated a-fluoro carbonyl compounds with enantiomeric excesses depending strongly on the structure of the metal enolate.119... 

A second general approach to allyl /(-lluorovinyl ether intermediates involves the reaction of a /J-fluoro alcoholate with an allylic halide. Claisen rearrangement then produces a-fluoro carbonyl compounds. Although the tremendous rate acceleration caused by a-fluoro substitution in the vinyl fragment is not present here, the rearrangements take place under synthetically useful conditions. 

A novel variation of the method of adding an allylie alcohol to a reactive a-fluoro carbonyl compound, as shown in the previous example, has been developed by Shi and Cai in a general strategy for the synthesis of /h/i-difluoro-a-amtno acids via the a-oxo esters 53.20 Ethyl tri-fluoropyruvate reacts with primary allylie alcohols 49 in benzene to form the stable hemiacetals... 

Trifluoromethyl hypofluorite smoothly converts silyl enol ethers into the corresponding a-fluoro carbonyl compounds in good yield (Table 5). ... 

Silvcr(I) tetrafluoroborate has been used to prepare a-fluoro carbonyl compounds from chlorinated epoxides.Minor byproducts of the reaction are the corresponding a-chloro carbonyl compounds. 

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). ... 

Reactions with organic compounds. HOF converts alkenes into a-fluoro alcohols, acetylenes mainly into a-fluoro carbonyl compounds [11], aromatic compounds (benzene and its monosubstituted derivatives, p-xylene, naphthalene) into phenolic products [12], and octa-ethylporphyrin into the N-oxide [13]. 

Many a-fluoro carbonyl compounds, which are intermediates or final products in the design of fluorinated analogs of biologically active compounds, were prepared by electrophilic fluorination this includes fluoro-tribactam antibiotics, 12-fluoroforskohn, 2-(/ )-fluorodehydroquinic... 

FIGURE 44.4. Examples of biologically active a-fluoro carbonyl compounds. 

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