Bromofluorination

Bromoethyl)benzene, reaction with ethyl phenylacetate, 47, 72 ic-Bromofluorides from olefins, 46,12 Bromofluorination of olefins, 46, 39... 

Hydrazoic acid reaction with cyclobu-tanecarboxyhc acid, 47, 28 Hydrogenation of t butylazidoacetate to glycme ( butyl ester, 46,47 Hydrogen bromide 46, 43 reaction with y butyrolactone, 46, 43 Hydrogen fluoride anhydrous, precautions in use of, 46, 3 in preparation of mtromum tetra-fluoroborate 47, 57 reaction with benzoyl chloride, 46,4 with boron tnfluonde in conversion of p cymene to m cymene, 47, 40 in bromofluorination of 1 heptene, 46, 11... 

HI, or Cdl2 iodofluorination with mixtures of AgF and U and mixtures of N-bromo amides in anhydrous HF give bromofluorination. Bromo-, iodo-, and chlorofluorination have also been achieved by treatment of the substrate with a solution of Br2,12, or an N-halo amide in polyhydrogen fluoride-pyridine while... 

Bromofluorination of double bonds using polymer-supported hydrogen fluoride-jV-bromosuccinimide (NBS) or BU4NF-NBS (Ref. 330) has been reported. 

Bromine, reaction with phenylacetylene and sodium hydroxide to give phenylbromoethyne, 46, 86 N-Bromoacetamide, as reagent for bromofluorination of 1-heptene, 46,10... 

On treatment of tri-O-acetyl-D-glucal with chlorine and silver fluoride,198 all four possible isomers were formed tri-0-acetyl-2-chloro-2-deoxy-a-D-mannopyranosyl fluoride (16%), tri-0-acetyl-2-chloro-2-deoxy-/3-D-mannopyranosyl fluoride (16%), tri-0-acetyl-2-chloro-2-deoxy-a-D-glucopyranosyl fluoride (6%), and tri-O-acetyl-2-chloro-2-deoxy-/3-D-glucopyranosyl fluoride (62%). These product ratios differ significantly from those of the corresponding bromofluorination and iodofluorination reactions of tri-O -ace tyl-D-glucal,43,53 and this behavior has been discussed198 in terms of the differences observed between the addition of bromine (or iodine) and chlorine to tri-O-acetyl-D-glu-cal, and the nature of the chlorination reaction itself. 

Transannular cyclization has also been observed in the bromofluorination of norbor-nadiene (49) using NBS in the presence of Et3N-3HF which led to a 3 2 mixture of... 

Nevertheless, a different selectivity has really been observed83 in bromofluorination reactions of 1,5-cycloalkadienes with NBS/Et3N-3HF or Olah s reagent. The reaction of 1,5-cyclooctadiene (3) with the former reagent yields mainly the 1,2-addition product 52, but when the reaction is carried out with Olah s reagent only compounds 53 and 54, arising from the usual transannular jr-cyclization, are formed (equation 53). 

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]. 

HF—Amine Complexes Complexes of fluorhydric acid (HF) with pyridine or alkyl amines (Et3N, Et2NH) are often utilized as reagents in nucleophilic fluorination reactions such as the opening of oxiranes," the bromofluorination of double bonds in the presence of NBS, or the diazotation/fluorination of amines with sodium nitrite (the Balz-Schiemann-like reaction) (Figure 2.1). ... 

BrF 98.92 20/ -33 + bromofluorinations, frequently in situ preparation of the agent from N-bromo-substituted amides and HF, HF-containing systems or AgF 4,7... 

Comparison of bromofluorinations of six substituted ethyl cinnamates using A-bromosuccin-imide with hydrogen fluoride/pyridine and hydrogen fluoride/tetrahydrofuran (several molar ratios) also shows a Markovnikov-type regioselectivity. The stereoselectivity depends on several factors 184... 

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... 

Furthermore, it has been found that larger carbocyclic 1,5-dienes195 or norbornadiene96,173 196 give halofluorinations with transannular participation of the second re-bond. A synthetically interesting example of a comparative study of selectivities in bromofluorinations of unsaturated... 

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 (A-bromosuccinimide in anhydrous hydrogen fluoride) and chloro-fluorination (hexachloromelamine in anhydrous hydrogen fluoride) of 2-chloroperfluorobuta-... 

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... 

Thechloro- and bromofluorination of vinyl chloride, 1,2-dichloroethene, trichloroethene, 1,2-dichlorodifluoroethene, and letrafluoroethene give good and for 3,3.3-trifluoropropene quantitative yields of the addition products. 

The acidic form of sodium fluoride, sodium bifluoride is scarcely used for introduction of fluorine in organic compounds. One reported example is the addition of bromofluorine to perfluoro(2-methylpent-2-ene) (20) generated by reacting A V -dibromodimethylhydantoin with acidic sodium fluoride in the presence of tetrabutylammonium hydrogen difluoride at 0°C to give 21.20... 

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. 

TBAF can be used for the bromofluorination of the 2-ethenylpyrrolidine derivative 15 in the presence of A-bromosuccinimide.211 For iodofluorination, see ref 212. 

Bromofluorination with Silicon Tetrafluoride and DBH General Procedure 4... 

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. 

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