Iodofluorination

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... 

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. 

IF 145.91 + + iodofluorinations, frequently in situ preparation of the agent from. V-iodo-substituted amides and HF, HF-containing systems or AgF 4, 7... 

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... 

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. 

Moreover, the same 2-fluoro-l-iodoalkanes (see Table 11) can be synthesized in yields of 60-94% by iodofluorinations of the corresponding alkenes using the tetrabutylammonium dihydrogen trifluoride//V-iodosuccinimide reagent in dichloromethane. This reaction is carried out in glassware for analytical details of the 2-fluoro-l-iodoalkanes, see ref 336 (for halofluorina-tions using tetrabutylammonium hydrogen fluoride//V-halosuccinimide in dichloromethane, see ref 337). 

However, it should be pointed out that the combination of iodochloride/hydrogen fluoride/ boron trifluoride is only efficient for the iodofluorination of terminal alkenes no corresponding iodide could be detected in reactions with perfluoropent-2-ene, even on prolonged heating (16 h) at 200 °C.341... 

Potassium fluoride-poly(hydrogen fluoride) salts are useful fluorine sources for bromo- and iodofluorinations of various alkenes (Method F).49 The best yields arc obtained with KH3F4 and KH4F5. The salts are prepared by mixing the calculated amounts of potassium hydrogen difluoride and anhydrous hydrogen fluoride in a reaction vessel made of polyethylene or Hastel-loy B. The mixture is stirred and heated at 60-70 C to form a homogeneous solution of the salt which solidifies at room temperature. 

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. 

A mixture of potassium hydrogen fluoride, 1 M hydrofluoric acid and (V-iodosuccinimide in the presence of tetrabutylammonium fluoride (TBAF) as a phase-transfer catalyst has been shown to effect iodofluorination of alkenes in good yield.163 Dodec-l-ene (6) has been transformed to 2-fluoro-l-iodododecane (7) in 82% yield. TBAF is essential for the reaction to proceed quickly and to improve the yield. The percentage of the side product 1-iodododecan-2-ol is kept to a minimum (0.2%). Many alkenes have been transformed to the corresponding fluoroiodo derivatives by this method.163... 

Iodofluorination of 1,9-dideoxyforskolin (9) at the 14,15-double bond affords the fluorinated product 10, which is further treated with a base for dehydroiodination and subsequent transformation.165... 

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. 

Electrophilic iodofluorination of fluoroalkenes (Scheme 5) has been reported to be the preferential pathway when earned out with IC1-HF in die presence of BF3. By contrast, if BF3 is absent, die reaction dims into iodochlorination as the mam pathway.30... 

In accordance with polarization of the C=C bond, iodofluorination of CF2=CXCF3 [50] and (CF3)2C=CF2 [49] starts with the attack of I+ electrophile on the central carbon of the olefin and results in each case in formation of a single regioisomer, (CF3)2 CFI and (CF3)3CI, respectively ... 

Recently it has been found that a combination of ICl/HF in the presence of a Lewis acid is effective for iodofluorination of fluoroolefins [50], For example, iodopentafluoroethane was isolated in 91 % yield in a reaction catalyzed by BF3 ... 

Niobium and tantalum pentafluorides are also effective catalysts for iodofluorination of TFE, while A1C13 and ZnCl2 show no activity. 

The double bond in F-pentene-2 is very stable to iodofluorination, and the starting material was recovered in the reaction of this olefin with IC1/HF/BF3 mixture after 24 h at 200 °C. Iodofluorination of polyfluoroolefins by the ICl/HF system [50] proceeds as conjugate addition (see Eq. 2) where the car-bocation generated as a result of the electrophilic attack of I+ on the C=C bond is stabilized by addition of F (pathway A). Formation of small amounts of C1CF2CF2I in this reaction could be a result of the reaction of the inter-... 

The iodofluorination of alkyl- or aryl-substituted alkenes is a trans addition which follows the Markovnikov rule. Some examples from the literature are compiled in Table 24. 

Further examples of the iodofluorination of halogenated alkenes are summarized in Table... 

The reagents for iodine fluoride addition to unsaturated centers are iodine229 or A -iodosuc-cinimide (NIS),221 258 and iodine pentafluoride, hydrogen fluoride,221,258 potassium fluoride, silver(I) fluoride229 278 or ammonium hydrogen difluoride/aluminum trifluoride220 as fluoride ion sources. In addition to the in situ iodofluorinations with iodine monofluoride,l96,22< 227 and (difluoroiodo)methane,194,19 iodofluorination with bis(pyridine)iodonium tetrafluoro-borate219 is described. 

Iodofluorination reactions of acetylenes can be carried out with iodine fluoride, prepared directly from the corresponding elements,553 with jV-iodosuccinimide in the presence of polymer-supported hydrogen fluoride,258 with (difluoroiodo)mcthane,554 or with bis(pyridine)iodonium tetrafluoroborate in the presence of fluoride.555 Some examples are summarized in Table 45. 

Iodofluorination of 1-Phenylalk-l-ynes with (Difluoroiodo)methane General Procedure 554... 

Ghlorofluorination with T-chlorosaccharin-HF/pyridine <1995SL327>, iodofluorination with T-iodosaccharin-HF/pyridine, and iodomethoxylation with A -iodosaccharin <2000SL544> of alkenes, alkynes, and activated aromatic compounds have been described. Bromohydrin and iodohydrin derivatives were prepared from electron-deficient alkenes and A -halosaccharins <2005EJO2349>. 

Starting materials for the synthesis of all perfluoroalkyl iodonium reagents are the perfluoroalkyl iodides, which themselves play a central role as building blocks in fluoroorganic chemistry. The iodides are available either by pyrolysis of the silver salts of perfluoroalkyl carboxylic acids in the presence on iodine [14] or - on a more technical scale - by iodofluorination of tetrafluoroethylene [15] with the iodine-IFp system [16] and subsequent radical telomerization of tetrafluoroethylene with the resulting intermediate perfluoroalkyl iodides [17] (Scheme 2.143). 

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