Reactions with perchloryl fluoride

Fluorination of sulfonamides 147 and 148 takes place upon deprotonation with NaH and reaction with perchloryl fluoride, FCIO3, to give products 149 and 150 (Scheme 19) <2000JOC7583, 2000CPB1954>. The resulting A-fluorosultams 149 and 150 have been used for the asymmetric fluorination of aryl ketone enolates (vide infra). 

Perchloryl fluoride generally reacts with electron-rich alkencs or with various carbanionie substrates (Scheme 1), where salts are usually prepared in situ and further react at low temperature or in some cases at room temperature temperature control must be taken into account. However. it has been pointed out several times that serious explosions may occur and for this reason the reactions are potentially hazardous and safety precautions must be taken when working with this reagent. Over the last twenty years fluorination reactions with perchloryl fluoride have been partially discussed in several monographs6 8 and review papers.9 12... 

Diethyl malonatc13 gives four products upon reaction with perchloryl fluoride diethyl difluoro-malonate, diethyl ethylmalonate, diethyl ethylfluoromalonate and diethyl fluoromalonate the product distribution depends on the reaction conditions. A number of esters are fluo-rinated,14 15 while (pentafluorophenyl)acetonitrile is converted into mono- and disubstituted products in the presence of cesium fluoride.16... 

Various steroids are fluorinated by conversion into the enolates, followed by fluorination with perchloryl fluoride to give the 16-fluorinated products 16.19 28 The Schiff base of 7-aminodeacetoxyeephalosporanic acid tart-butyl ester is converted into an anion with potassium tm-butoxide,29 while further reaction with perchloryl fluoride diluted with nitrogen at — 50 C gives 7-(benzylideneamino)-7-fluorodeacetoxycephalosporanicacid fer/-butyl ester (17) in high yield. An attempt to prepare 2-fluoropodophyllotoxin by reaction of the enolate with perchloryl fluoride resulted in a violent explosion.30... 

Lithiotellurophene and ethyl nitrate did not react to produce 2-nitrotellurophene3. Reaction with perchloryl fluoride did not convert 2-lithiotellurophene to 2-fluoro-tellurophcnc3. 

Caution Two laboratories have reported serious explosions in reactions with perchloryl fluoride. 

EXPLOSION and FIRE CONCERNS combustible solid, liquid and vapor above 88°C, may form explosive vapor-air mixtures NFPA rating Health 3, Flammability 2, Reactivity 0 contact with strong oxidizers may cause fire reacts violently with lead dioxide forms an explosive product on reaction with perchloryl fluoride violent reaction with 2-phenylamino-3-phenyloxazirane very dangerous heating to decomposition produces carbon dioxide, carbon monoxide, and toxic fumes of oxides of nitrogen use water spray, alcohol foam, powder or carbon dioxide for firefighting purposes. 

Halogenation of a Cxe -macroUde. Reaction of the pyrrolidine enamine of the antibiotic leucomycin A3 (1) with NBS yields, after hydrolysis, the 17-bromo derivative (62%). A similar reaction is observed with NCS (66%, yield). In contrast, reaction with perchloryl fluoride in limited amounts results in fluorination at Ci, and Cm. The Cm-rnonofluoride was made indirectly by reaction first with NBS and then with perchloryl fluoride the bromofluoro... 

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 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. 

A novel reaction of perchloryl fluoride with aromatic substrates was discovered by Neeman and Osawa, the oxofluorination reaction. These authors found that reaction of indene with perchloryl fluoride in dioxane-water yields five products, the major product being, 2-fluoroindanone. When applied to 6-dehydroestradiol diacetate (24) there is obtained as the major product the 7a-fluoro-6-ketone (25). Borohydride reduction of the... 

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. 

The pyrrolidine enamines of /l -3.]cetosteroids (111), on alkylation with methyl iodide, gave mainly the N-alkylated product (5,55) in nonpolar solvents such as benzene. The reaction in more polar solvents gave the 4-methylated product (5.S). The reaction of (111) with perchloryl fluoride involves attack at the C-4 atom to give, after acid hydrolysis, either 4-fluoro-zJ -3-ketone (119) or 4,4-difluoro-zJ -3-ketone 120), depending on the reaction conditions (59). 

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-... 

S. Nakanishi, R.L. Morgan, E.V. Jensen, 4-Fluorinated steroids from the reaction of perchloryl fluoride with steroid enamines, Chem. Ind. (London) (1960) 1136-1137. 

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-... 

A number of cycloalkyl-, vinyl-, aryl-, and benzyllithium compounds (predominantly benzyl-lithiums) are converted into fluoro derivatives in good to excellent yields, e.g. formation of 4, 5, and 6 19 however, when this method was applied to the synthesisof 3-fluorobenzocyclobutene from the lithium salt a violent explosion occurred when the reaction mixture was warmed from — 70 C to room temperature.20 Various fluoro-substituted thiophenes 7 are obtained when the starting compounds (thiophene, 2-methylthiophene, etc.) arc transformed with al-kyllithium compounds to the corresponding lithium derivatives then fluorinated with perchloryl fluoride at 0 C.21 Potassium tricyanomethanidc is converted at —15 C in triglyme into tricyanofluoromethane in 81 % yield.22... 

Amines react with perchloryl fluoride. Thus, l-fluoro-2,2,6,6-tetramethylpiperidine (22) is form ed from the piperidine derivative 35 on the other hand, 1-fluoro salts 23 can he prepared by reactions with l-alkylpiperidines.36... 

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