Monofluorinations, /3-ketoesters

The fluorination of P-diketones and p-ketoesters with N-/luorobis(trifluo-romethanesulfonyl)imide (Table 3a, B) can be controlled to give either mono-fluorination or difluorination. Monofluorination occurs when the strong acid, bis(trifluoromethanesulfonyl)imide, a reaction product, is removed by addition of water, which prevents further enolization and fluormation of the monofluoro adduct [83] (equation 38)... 

DFIT has been employed with pyridine 9HF for monofluorinations of /3-ketoesters [104]. Similar a-fluorinations can be effected by electrolysis of Et3N 5HF solutions, containinglil mixtures of p-iodotoluene and jS-dicarbonyl compounds, in an undivided cell at 0°C. In this procedure, DFIT is generated in situ and mediates fluorination of the substrate (Scheme 34) [97]. 

The importance of a-fluoro-p-ketoesters stems from their use as synthons in the preparation of biologically active monofluorinated heterocycles(45) and fluorinated isoprenyl derivatives (46) which have found application as hyperlipidemic drugs (47), as hormone substitutes (48), and in cancer chemotherapy (49). 

Stuart and co-workers have reported on a novel, stable fluorinating reagent based on a cyclic hypervalent iodine(m) skeleton typically used for trifluoromethylation. Model studies for the reagent focused on the fluorination of ethyl-3-oxo-3-phenylpropanoate and showed that addition of TREAT-HF (triethylamine trihydrofluoride) is essential for the reaction to proceed. Judicious control of stoichiometry, concentration, and temperature allowed good yields of the monofluorinated compound to be obtained (Scheme 15.37). No fluorination was observed in the absence of the fluor-oindane. A range of p-ketoesters and 1,3-diketones were evaluated under the optimal conditions, and it was shown that the relative reactivity could be directly correlated with the substrate s enol content, as observed previously... 

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