Perchloryl fluoride synthesis

Blackburn, G.M., England, D.A., and Kolkinann, F., Monofluoro- and difluoro-methylenebisphospho-nic acids, Isopolar analogues of pyrophosphoric acid, J. Chem. Soc., Chem. Commun., 930, 1981. McKenna, C.E., and Shen, P.-D., Fluorination of methanediphosphonate esters by perchloryl fluoride. Synthesis of fluoromethanediphosphonic acid and difluoromethanediphosphonic acid, J. Org. Chem., 46, 4573, 1981. 

Miscellaneous Reactions.- The Schlosser-Wittig reaction of ylide (209) with aldehyde (208) and treatment of the intermediate 6-oxido ylide with perchloryl fluoride has been used to construct the 13-fluoro unit (210) in a total synthesis of (+)-13-fluoroprosta-... 

R.E. Ehrenkaufer, R.R. MacGregor, Synthesis of [ F]-perchloryl fluoride and its reactions with functionalized aryllithiums, Int. J. Appl. Radiat. Isot. 34(1983)613-615. R. Chirakal, G. Firnau, J.G. Schrobilgen, J. McKay, E.S. Garnett, The synthesis of [ F]xenon difluoride from [ F]fluorine gas, Int. J. Appl. Radiat. Isot. 35 (1984) 401-404. 

A synthesis of the B-ring aromatic corticosteroid (286), the analogue of cortex-olone, started with the previously reported B-ring aromatic norpregnane (285). Development of the corticosteroid side-chain employed bromination of the 17a-hydroxy-20-oxo-derivative with trimethylphenylammonium bromide perbromide. " Reaction of perchloryl fluoride with the mixed enol ethers (287) and (288) provided, after hydrolysis, the 17a-fluoro-20-oxo-compound (290) and the 21-fluoro-20-oxo-compound (291). In contrast, the enamine (289) led only to the 17a,21-difluoro-20-oxo-compound. A series of 17a-acyloxy-21-deoxy-... 

Mono- and Difluoro Derivatives of Methylene-diphosphonic Acid Synthesis with Perchloryl Fluoride... 

Perchloryl fluoride, which is a gentle reagent, does not react with alcohols, aldehydes and normal double bonds but does react with aliphatic or aromatic anions. It was instrumental in the synthesis of chlorofluoro and difluoro malonaldehydes (equation 127)227 and of fluoroaromatics such as fluoroveratrole228 and fluorotamoxifen 22 (equation 128)229, both having considerable biological potential. 

Finally, an example of fluorination of the C = P bond has been reported." Reaction of the /1-oxido ylide 22 with gaseous perchloryl fluoride at — 35 C gives the fluoroalkenes 23A and B in 12 and 45 % yield, respectively. Alkene 23B is an intermediate in the synthesis of (-F)-13-fluoroprostaglandin methyl ester, a compound with antifertility and muscle-stimulating effects. 

A number of 3-fluoro-steroids have been prepared, using either Et2NCF2CHClF or CF3OF as reagent. The synthesis of 14/i-fluoro-, -bromo-, and -chloro-androstanes and -oestratrienes by reaction of the corresponding A " -diene 17-acetates Avith perchloryl fluoride has also been reported " (see Part II, Chapter 1, refs. 271, 275, 276, and 148). 

Scheme 2.78 Synthesis of fluorosteroids by electrophilic fluorination with perchloryl fluoride.

The full paper on the synthesis of 14 -fluoro-steroids by perchloryl fluoride fluorination of A -17-acetates has now appeared. It has been shown that 16a-bromoacetoxyprogesterone alkylates cysteine, histidine, methionine, lysine, and /5-mercaptoethanol under physiological conditions. 

Fluorine may be introduced into the 5-position of 5-alkyl- and 5-aryl-barbituric acids by use of perchloryl fluoride, FCIO3, in mcthanol. The synthesis of l-(tetra-... 

Halogenated thiophenes, which are important intermediates for the synthesis of further substitution patterns, can be generated by the reaction of thienyllithium derivatives with sources of electrophilic halogens. Fluorination is possible using perchloryl fluoride forming the corresponding product 95 in moderate yield (Scheme 39) [20, 238-240]. Chlorine can be introduced by the reaction of thienyllithium with chlorine, hexachloroethane, trichloroacetonitrile, or sulfonyl chloride [20, 173, 180, 226, 229, 240-244]. Tetrabromomethane is used for bromi-nations [245] and aUcyl iodides for iodinations (Scheme 40) [24, 123, 246-250]. 

Methods for the synthesis of fluorobenzothiophenes are rare. A lithiation-fluorination sequence by treatment of benzothiophenes 57 with n-BuLi followed by fluorination with perchloryl fluoride [35], N2F2 [36], or N-fluorodibenzenesulfonimide afforded 2-fluorobenzo[h]thiophenes 58 in good yields [37]. 

In 1999, both enantiomers of the fluorinated analog were obtained using LiHMDS and perchloryl fluoride as an electrophilic source of fluorine in 71% yield. After several steps, the enantiomers were separated using chiral high-performance liquid chromatography (HPLC) and biologically evaluated. More recently, the first enantioselective synthesis of both enantiomers of thalidomide was described with the aid of a chiral [N-F]+ reagent obtained by combination of a cinchona alkaloid, dihydroquinine (DHQ), and... 

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