Ketones fluoro

The reaction with the jff,y-unsaturated A °k3 ketone (20) in pyridine proceeds in 25% yield to the 10j -fluoro ketone (21). a,yS-Unsaturated ketones do not react with perchloryl fluoride. 

C—O bonding and Cl—F fission of the intermediate cw-fluoro chlorate (29a), which in turn undergoes oxidation to the fluoro ketone (25) by a concerted elimination of chlorous acid. A similar transition state (30) approximating an allylic carbonium ion could be involved in the reaction of the dienol derivatives (6) with perchloryl fluoride, which would be expected to give rise to the c/5-adduct (30a). Reaction of the latter with water leads to product and chlorate ion. 

A -Steroids react sluggishly with nitrosyl fluoride to yield after alumina chromatography the nitro-olefin (44) (14 %), and 0.7 % of the 2a-fluoro ketone (45), the former probably arising by alumina-catalyzed dehydrofiuorination of an intermediate 2-fluoro-3-nitro adduct. 

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]... 

Huonnations with DAST proceed with high chemoselectivity In general, under very mild reaction conditions usually required for the replacement of hydroxyl groups, other functional groups, including phenolic hydroxyl groups [112], remain intact This provides a method for selective conversion of hydroxy esters [95 97] (Table 6), hydroxy ketones [120, 121], hydroxy lactones [722, 123], hydroxy lactams [124] and hydroxy nitriles [725] into fluoro esters, fluoro ketones, fluoro lactones, fluoro lactams, and fluoro nitnles, respectively (equations 60-63)... 

A special application of heteroaromatic acylation via a modified Dakin-West reaction leads to a-fluoro ketone derivatives [50] (equation 30) Such fluoro ketones have been successfully used as enzyme inhibitors in modern bioorganic chemistry [5, 6]... 

Another well-established process to generate fluoro ketones proceeds via acylation ofenolates [68, 69] or activated methylene compounds [70 71] as well as by Claisen type condensation reactions [72] Because of the electrophilic power of the acylating agents, there is usually no need tor a catalyst [68]... 

When diazo ketones are treated with HBr or HCl, they give the respective a-halo ketones, but HI does not give the reaction, since it reduces the product to a methyl ketone (10-87). a-Fluoro ketones can be prepared by addition of the diazo ketone to polyhydrogen fluoride-pyridine. This method is also successful for diazoalkanes. 

The use of chiral a-fluoro ketone G can lead to enantioselective epoxidation.106... 

The reaction232-235 (see also Ref. 236) of 1-diazoketones with hydrogen fluoride that affords 1-fluoro ketones has also been applied to carbohydrates, with, however, no success. Treatment of 3,4-di-O-benzoyl-1-deoxy-l-diazo-D-gfycero-tetrulose with hydrogen fluoride in ether mainly afforded 3,4-di-O-benzoyl-D-gfycero-tetrulose, whereas, with hydrogen bromide and chloride, 3,4-di-O-benzoyl-l-bromo-l-deoxy-and 3,4-di-O-benzoyl-l-chloro-l-deoxy-D-gfycero-tetrulose, respec-... 

Recently, Crousse and coworkers reported that new fluoro ketones serve as efficient catalysts for the epoxidation reactions with Oxone in hexafluoropropan-2-ol (HFIP) (equation 46). ... 

M.H. Gelb, J.P. Svaren, R.H. Abeles, Fluoro ketone inhibitors of hydrolytic enzymes, Biochemistry 24 (1985) 1813-1817. 

Substituted 2//-azirines are readily transformed into 2,2-difluoroethylamines160168 by treatment with hydrogen fluoride/pyridine to give the products in moderate yield. Depending on the substituents, a-fluoro ketones are also formed in some cases.160169 Increased yields are obtained under similarly mild conditions with a weakened hydrogen fluoride system from 30% hydrogen fluoride/pyridine plus triethylamine.169... 

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... 

Enol acetates, oxo esters, nilroalkenes33 and sodium salts of various esters have been successfully converted into fluoro ketones and esters by acetyl hypofluorite, trifluoroacetyl hypofluorite or mixtures containing acetyl hypofluorite and fluoroxy compounds.3 4 -10-12-13 Examples are the formation of l-fluoro-l,3-diphenylacetone (12), a-fluoro-/i-oxo esters 13, a-fluoro ketones 14 and 15. ethyl l-fluoro-2-oxocyclopentanecarboxylate (16), and 2-fluoromalonate 17. 

Regioselective fluorodestannylation of alkenyl and heteroaryl molecules to give 34 can be achieved under mild conditions with cesium fluoroxysulfate, while x-fluoro ketones, e.g. 35, are formed when the tin group is attached to the benzylic position.42 The pyrrole ring in indole derivatives is also successfully fluorinated using this method, e.g. formation of 36.42-45... 

Aliphatic a-hydroxy ketones react with sulfur tetrafluoride, generally to provide trifluoroal-kanes. However, under carefully chosen conditions the carbonyl group in hydroxy ketones remains intact while the hydroxy group undergoes selective substitution by fluorine. Thus, 5-hydroxyoctan-4-one reacts with sulfur tetrafluoride (20°C, 3 h) to give a 1 1 mixture of 5-fluorooctan-4-one(l b) and 2-oxo-l-propylpentyl fluorosulfite.63 a-Fluoro ketones 1 are formed in high yield and as the sole product when diethyl ether is used as solvent.64... 

Direct regioselective conversion of a variety of cyclic and acyclic ketones to a-fluoro ketones was achieved in high to excellent yield using NFTh (21) in acetonitrile solution.96 The collected results (Table 10) of this highly effective direct transformation show that a comprehensive range of ketones can be fluorinated a to the carbonyl group, without prior activation. 

Fluoropregn-5-en-20-one, 437 2a-Fluorocholestanone, 475 2a-Fluorocortisone BMD, 485 2-Fluoroindanone, 477 Fluoro ketones and vinylogous fluoro ketones, 474... 

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