Alkenes halofluorination

As a rule, alkynes react in bromo- and iodofluorinations by monoaddition because vinylic a./f-halofluorides as electron-deficient alkenes are generally less reactive. However, some aryl-conjugated alkenes, such as cinnamate or stilbene derivatives 3 or 5, respectively,184 may also be halofluorinated by hydrogen fluoride/pyridine/A-halosuccinimide reagent.185... 

The combination of A/-halosuccinimides with polyfluorinated ammonium salts, in particular A/-halosuccinimide-triethylamine trisfhydrogen fluoride)42 (Method C), is convenient and effective for the halofluorination of alkenes. These easy-to-handle reagents allow work to be carried out at room temperature in conventional glass apparatus, while Olah s reagent requires polyethylene equipment. The reaction of various alkenes with A -halosuccinimide-triethylamine trisfhydrogen fluoride) in dichloromethane or diethyl ether at 0 C is complete within 3-5 hours giving the halogen fluoride addition products in 70-95% yield. 

Halofluorination of Alkenes with the, V-Halosuccinimide-F.t, N 3HF System General Procedure (Method C) 42... 

Table 2. Halofluorination of Alkenes and Alkynes with Stoichiometric Equivalents of Halogen Fluorides...

Silver(I) fluoride dispersed on the surface of finely powdered calcium fluoride shows improved fluoride nuclcophilicity for addition to alkenes in halofluorination reactions.56 For example, hex-1-ene with l,3-dibromo-5,5-dimethylhydantoin and silver(I) fluoride/calcium fluoride in dichloromethane at 20 C gives, within 1 hour, l-bromo-2-fluorohexanc in 90% yield while with silver(I) fluoride, under similar conditions, the yield is only 39%. 

Boron trifluoride and boron trifluoride-diethyl ether complex can be used as a source of fluoride ions in the presence of hypobromites and hypochlorites, e.g. methyl hypobromitc, tert-butyl hypobromite, methyl hypochlorite in carbon tetrachloride at 25 C. The addition of bromine monofluoride" and chlorine monofluoride" to various alkenes is accompanied by the formation of the corresponding alkoxybromides and alkoxychlorides which hinder the isolation of the halofluorinated products.57 jV-Bromo- and A -chloro-substiluted alkyl- and arylamines. -amides, and -imides, A -chloro-A,-methylamine, A -bromo-A -methylamine, A -chloro-A, /V-dimethylamine, A-bromo-A.A-dimethylamine, ACV-dichloro-A -methylamine, V,fV-dibromo-,V-mcthylaminc, A -bromosuccinimide, -V-chlorosuccinimide, Af-bromoacct-amide, A.A -dichlorourethane, can be used in the reaction instead of the hypohalites. The reactions with various alkenes conducted in dichloromethane at room temperature in the presence of boron trifluoride-diethyl ether complex produce bromofluoro and chlorofluoro addition products in 40-80 % yield. However, the reactions are complicated by the addition of A -halo-succinimides and Af.A-dichlorourcthane to the C = C bonds.58... 

Alkenes are converted into the corresponding bromofluorides by reaction w ith 1,3-di-bromo-5,5-dimethylhydantoin and silicon telrafluoride in aqueous dioxane in a highly regio-and stereoselective manner,54 Both A-ehlorosuecinimide and A/-iodosuccinimide arc ineffective in this halofluorination. 

Several groups have employed N-halosuccinimdes for the halofluorination of alkenes. Laurent and co-workers have found that triethylamine tris(hydrofluoride) is a suitable fluoride source for the halofluorination of a number of alkenes (Scheme 70).137 Other examples of halofluorinations include NBS and tetrabutylammonium fluoride as the halogen sources for the formal addition of BrF across funtionalized cyclohexenes138 and the halofluorination of alkenes and alkynes by all three N-halosuccinimides and polymer-supported HF.139... 

Likewise, Kuroboshi and Hiyama60 reported that regio-, stereo- and chemoselective halofluorination of alkenes is achieved using iV-halo imides and tetrabutylammonium dihydrogen trifluoride (equation 41). They also noted that the fluorine is always introduced... 

The reaction has been used extensively for the introduction of fluorine into steroids [277], where a curious anomaly arises between BrF and IF addition. As indicated, stereospecific anti addition occurs in most reactions but syn addition of BrF or IF to carbohydrates has been observed [278]. Halofluorination of alkynes proceeds as expected, although further reaction of the resulting alkene derivative can occur. 

In a similar process to halofluorination, sulphur- [285], selenium- [286] and nitrogen-containing [43] groups and fluorine may be added to hydrocarbon double bonds by reaction of an alkene with an electrophilic reagent of the heteroatom species in conjunction with a fluoride-ion source (Figure 3.66). As expected, Markovnikov addition in trans stereochemistry occurs mainly. 

HF-pyridine reagent, however, can also be used for the hy-drofluorination of alkenes,7 alkynes,7 cyclopropanes,7 and diazo compounds,8 the halofluorination of alkenes,9 the preparation of fluoroformates from carbamates,10 the preparation of a-fluorocarboxylic acids from a-amino acids,11 and as a deprotecting reagent in peptide chemistry.12 Examples of the hydrofluorination of alkenes with HF-pyridine are given in Table II. 

Alvemhe G, Haufe G, Lawrent A. 1987. Triethylamine tris-hydrofluoride [(C2H5)3 N.3HF] a highly versatile source of fluoride-ion for the halofluorination of alkenes. Synthesis 6 562-564. 

Type of reaction C-F and C-halo bond formation Reaction conditions Dichloromethane, room temperature Synthetic strategy One-step halofluorination of alkenes Catalyst Trihaloisocyanuric acid (TXCA) / HF-pyridine... 

Keywords Alkenes, trihaloisocyanuric acid (TXCA), HF-pyridine, dichloromethane, room temperature, regioselective halofluorination of alkenes, vicinal halofluoroalkanes... 

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