Fluorination with perchloryl

Several phenyllithium compounds were fluorinated with perchloryl p F]fluoride ([ F]FCI03, Scheme 21) to produce the corresponding p F]fluorobenzenes (2-[ F]fluoroaniline, 2-p F]fluoroanisole and 3-[ F]fluoroveratrole) in 21-34% radiochemical yields [79],... 

Introduction of Fluorine with Perchloryl Fluoride (FC103)... 

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... 

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... 

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

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]. 

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 fluonnation of both mono and dinitro enolates proceeds well with perchloryl fluoride. The mononitro fluorinated intermediates have been used to develop fluorinated materials of general synthetic utility [III, 113] (equation 63)... 

Fluorination of the ester with perchloryl fluoride by an established method led to... 

Carbanions in the form of organomagnesium, -sodium, or -lithium salts have been fluorinated with various reagents, including perchloryl [ F]fluoride, 1-[ F]fluoro-2-pyridone, A/-[ F]fluoropyridinium triflate and A/-[ F]fluoro-A/-alkylsulphonamides. 

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... 

Testosterone enol diacetate reacts with perchloryl fluoride in aqueous dioxane to give 6a- and 6/i-fluorotestostcrone 17-acetatc (18 X = a-F, /i-F) as the major products along with 6a- and 6/3-hydroxytestosterone 17-acetate (18 X = a-OH, /j-OH) and also 17/i-hydroxyandrostane-3,6-dione 17-acctate.31 The enamine derivative 3-(pyrrolidin-l-yl)estra-3,5-dien-17/i-ol can be fluorinated in methanol at —25 to — 35 C to provide 4/J-fluoro-3a-methoxycstr-5-ene-3/f 17/ -diol (19),32 while various 2-fluoro-3-oxoestranc derivatives 20 are formed by fluorination of a number of 3-methoxyestrane derivatives in tetrahydrofuran/water mixture with perchloryl fluoride.33... 

Derivatives of barbituric acid (10.28) are so reactive in the presence of halogens that it is often difficult to obtain the 5-monohalogenated derivatives [21CB1035 22CB3400 74JCS(P1)2095 79JOU357], 5,5-dihalo compounds being obtained. Fluorination of 5-substituted barbiturates with perchloryl fluoride was shown to be first order in each component. Elec-... 

In general, examples of substitution of sodium and potassium in organometallic derivatives by fluorine are limited to the salts of active methylene compounds. Their fluorination is achieved with perchloryl fluoride.fluorine, N-F reagents. " and xenon difluoride " (Table 10). The fluorination of metal enolates is discussed under metal-assisted substitution ot... 

Metal enolates can be fluorinated successfully with perchloryl fluoride, e.g. formation of 4,"" but due to the aggressive nature of perchloryl fluoride its applications are limited " (caulion see Vol.ElOa, p265ff). Alternatively, fluorination can be performed by acetyl hypofluorite... 

Interesting fluorinated estradiol analogs have been prepared from 4-fluoroestradiol (6), which is obtained from 19-nortestosterone (3) via fluorination of enamine 4 with perchloryl fluoride to give 4-fluoro-19-nortestosteronc (5), followed by selenium dioxide aromatization. ... 

Fluoro-l9-nortestosterone (5) Typical Procedure for the Fluorination of Enamines with Perchloryl Fluoride " ... 

Fluorinations using perchloryl fluoride (FCIO3) have been reported [17, 142] but, since the perchloric acid that is formed as a side-product gives an explosive mixture with organic compounds, this approach to selective fluorinations is not recommended. 

Although the majority of radiopharmaceuticals labeled with fluorine-18 have been prepared using nucleophilic fluorination reactions, in a few instances the application of electrophilic fluorination reactions has proved quite suitable. The most significant limitation of electrophilic 18F-fluorinations is the relatively low specific activities (less than lOCi/mmol) commonly obtained for final products. This is a result of the fact that electrophilic 18F-fluorination reagents (perchloryl fluoride, acetyl hypofluorite, xenon difluoride, A-fluoro-zV-alkylsulfonamides, diethylaminosulfur trifluoride) are prepared in low specific activity from 18F-labeled fluorine gas, which in itself produced in a carrier-added fashion. A second drawback of electrophilic fluorination is that the maximum radiochemical yield obtainable is 50%, as only one of the two fluorine atoms in fluorine gas can end up in the product (or, for preparation of electrophilic reagents such as acetyl [18F]hypofluorite, the maximum yield of preparing the reagent from [18F]F2 is 50%). 

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