Fluorinated ketones, reaction with enamines

Fluorme-containing Michael addition acceptors have been used as synthons, a portion of a molecule recognizably related to a simpler molecule, for the introduction of fluorine into the organic molecules Their reactions with enamines and ketones lead to a condensarion-cyclization process... 

Similarly, fluorinated ketones are prepared and react with enamines [50], This reaction involves the intermediacy of an a,P-ethylenic ketone and leads to annelation-aromatization products [5tJ] (Table 13) (equation 37). 

A direct and safe method for making a-fluorinated cyclic enones of possible therapeutic interest involves the reaction of CH2=CHFCOMe with enamines or alkali enolates. Thus, 3-fluoro-l 0-methyl-1,9-A-2-octalone was prepared regio-specifically from the fluorovinyl ketone and 2-methylcyclohexanone in Bu OH at... 

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-... 

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... 

Also covered in this section is the fluorination of enamines with electrophilic fluorine ( F+ ). This reaction is not really a substitution of a monovalent nitrogen (amino) group by fluorine, but in this method the enamine group of the substrate is substituted, although in another position, by fluorine in the a-fluoro ketone product. 

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... 

Thus, treatment of enamines with BuLi yields the lithiated species, which was selectively C-methylated to give the corresponding a-methyl-substituted enamines in good yields. The reaction of the enamines with a, 8-unsaturated ketones is also explored (eq 73). Furthermore, the lithio-enamines undergo 1,2-addition to unsaturated ketones to give intermediates, which, upon cycliza-tion and prototropic rearrangement, provide a regioselective de novo synthesis of fluorinated pyridines. 

Route B is also versatile and efficient (/-/,/5), allowing for the preparation of iV-aryl, A -alkoxycarbonyl and also A -unsubstituted polyfluoroalkyl enamines and imines in good to excellent yields. Starting material in this case are fluorinated p-sulfmyl ketones 7, which were submitted to Staudmger (aza-PP/7%) reaction 16,17) with iminophosphoranes 8. Monofluorinated ketones 7 were found to be poorly reactive when submitted to the Staudinger reaction, therefore low yields (10-30%) of the corresponding products were generally obtained. No reaction was achieved with nonfluorinated 3-ketosulfoxides. 

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