Alkene bromofluorination

Nucleophilic displacement using [ F] fluoride works well in aUphatic systems where reactive haUdes or sulfonates esters can undergo substitution at unhindered sites. In order to introduce a F fluorine atom in a secondary or tertiary position, a two steps strategy was developed. It involves a F-bromofluorination of alkenes, followed by reductive debromination (n-BujSnH, AIBN). [ F]BrF is usually generated in situ from [ F]potassium fluoride and l,3-dibromo-5,5-dimethylhydantoin (DBH) in sulfuric acid. This methodology was successfully applied to label steroids at the 11 and 6a positions [245] (Scheme 60) and to prepare [ F]fluorocyclohexanes [246]. 

Iodofluorination and bromofluorination of alkenes are also effected in hydrogen fluoride systems by using bromine or iodine with an equivalent amount of silver(I) nitrate. In some cases, iodofluorination can also be achieved by iodine without adding the silver(I) salt, as illustrated in the following procedure. 

Selected examples are given in Table 9 for bromofluorinations of alkenes using A-bromosuccin-imide in combination with 70% hydrogen fluoride/pyridine (Method A) and hydrogen fluo-ride/polyvinylpyridine (Method B), respectively. Table 10 shows examples of the selective monoaddition of in situ produced halofluorides (70 % hydrogen fluoride/pyridine and A-iodo-. A-bromo- or /V-ehloro-succinimide) to symmetrically substituted alkynes. 

Bromofluorination of dodec-2-ene, styrene, and methyl undec-10-enoate are carried out using similar conditions but using l,3-dibromo-5,5-dimethylhydantoin instead of A-halosuc-cinimide however, chlorofluorination with A-chlorosuccinimide as a chlorinating reagent is not successful at all and starting alkenes are recovered unchanged.336... 

The addition of bromine monofluoride to alkenes using equimolar quantities of /V-bro-moamides in excess anhydrous hydrogen fluoride gives the expected l-bromo-2-fluoroalkanes and small amounts (3-8 %) of isomeric 2-bromo-l-fluoroalkanes.29 1-Bromo-2-fluoroheptane can be prepared in 60-77% yield from hept-l-cnc, /V-bromoacetamide and hydrogen fluoride in diethyl ether at — 78"C.30 The bromofluorination of methyl methacrylate (1) with 1,3-di-bromo-5.5-dimethylhydantoin (DBH) and liquid hydrogen fluoride exemplifies this procedure.31... 

Bromofluorination of phenyl-substituted alkenes. e.g. 1,1 -diphenylethene. /(-alkylstyrenes, stilbene,3h 1-phenylcyclohexene,37 cinnamates, and a-fluorocinnamates,38 with A-bromosuc-cinimide-hydrogen fluoride/pyridine in diethyl ether proceeds with Markovnikov-type re-gioselectivity. The reaction is stereospecilic anti) for E- and nonstereospecific for Z-alkenes due to the large extent of isomerization of the latter under the reaction conditions. 

Bromofluorination of Phenyl-Substituted Alkenes Using the NBS-HF/Pyridine System (Method A) General Procedure 38... 

Bromofluorination of Alkenes with the DBH/PVPHF (64/36) System l-Bromo-2-fluorocyclohexane Typical Procedure (Method B) 41... 

The products formed in the bromofluorination and iodofluorination of alkenes 1 with KH4F5/ DBH and KH Fj/A -iodosuccinimide are given in Tables 8 and 9, respectively. 

AflaskconlainingasolutionofDBH(l.l mmol) and H20 (1.1 mmol) in 1,4-dioxane (4 mL) was connected to a balloon filled with SiF4 ( 100 mL) and the mixture was stirred at rt for 15 min. A solution of alkene (1.0 mmol) in 1,4-dioxane (1 mL) was added, and the mixture was stirred at rt for 2-3 h. Sat. aq KF (5 mL) was added to the mixture, and after normal workup, the resulting crude mixture was purified by flash silica gel column chromatography to give the bromofluorinaled product. 

Bromofluorination 2 followed by the present procedure is a general way to convert 1 alkenes to 2-fluoroaIkanoic acids similar results have been obtained with ethylene, propylene, 1-butene, 1-hexene, 1-octene, 1-decene, and methyl 10-unde-cenoate.5 It is an easy and convenient way to make 2-fluoroalka-noic acids, for it requires only conventional apparatus and readily available intermediates. 

Stable dialkyl ether poly(hydrogen fluoride) complexes have been shown to be convenient and effective fluorinating agents.553 Various open-chain and cyclic alkenes undergo hydrofluorination with dimethyl ether-5 HF (DMEPHF) atroom temperature to furnish the corresponding fluoro derivatives in high yields (73-94%) with excellent selectivities. The fluorination of secondary and tertiary alcohols exhibit similar features. Bromofluorination of alkenes can also carried out with DMEPHF in combination with /V-bromosuccinimide. The homologous diethyl ether and dipropyl ether complexes are also suitable for fluorinations. 

Fluorinatioa.1 Alkyl bromides are converted to alkyl fluorides by reaction with this reagent in CFI3CN (35-92% yield). Bromofluorination of alkenes can be effected with AgF/CaF2 and l,3-dibromo-5,5-dimethylhydantoin (DBH). Iodo-... 

More examples of bromofluorination reactions of halogenated alkenes are listed in Table 22. while further reactions are those of 9 and 10. 

Further examples of bromofluorinations of substituted alkenes are summarized in Table 23 and given by the formation of 13 and... 

The addition of bromine fluoride to cyclohexene occurs highly stereospecifically to yield the fran.v-adduct. Further examples of the bromofluorination of cyclic alkenes with various reagents are reported in Table 21, and also given by the reactions of norbornene (2), 70,21 5 228 benzo-norbomene (4).2 2 8 and norbornadiene (5).112-215... 

Bromofluorination followed by the present procedure is a general way to convert 1-alkenes to 2-fluoroalkanoic acids similar results have been obtained with ethylene, propylene,... 

BROMOFLUORINATION OF ALKENES 1-BROMO-2-FLUORO-2-PHENYLPROPANE (Benzene, (2-bromo-1-fluoro-1 -methylethyl))... 

This method for bromofluorination of ethylenic compounds has been extended by others to symmetrical alkenes,10 terminal allylic alcohols,11 vinyl oxiranes,12 enol esters,13 and vinyl fluorides.14... 

BROMOFLUORINATION OF ALKENES WITH THE REAGENT COMBINATION N-BROMOSUCCINIMIDE/TRIETHYLAMINE TRISHYDROFLUORIDE... 

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