Hypofluorites formation

It appears that hypofluorite formation occurs by nucleophilic attack via the very weakly nucleophilic perfluoroaUcoxide ions on elemental fluorine, regenerating fluoride ion, because the process is catal3dic in alkali-metal fluoride (Figure 8.37). 

Formation of perfluoroalkyl hypofluorites (which are more stable than AcOF) by the reaction of NaO(0)CCF3 and Fj, and the reaction with 61 (to give 2DFG), have been reported. ... 

Fluorination of caesium heptafluoropropoxide at —40°C with nitrogen-diluted fluorine exploded violently after 10 h. This may have been caused by ingress of moisture, formation of some pentafluoropropionyl derivative and conversion of this to pentafluoropropionyl hypofluorite, known to be explosive if suitably initiated. Other possible explosive intermediates are peroxides or peresters. 

Barton and co-workers have explored tertiary carbon atom functionalization by trifluoromethyl hypofluorite, mainly in chloroform, on various steroid derivatives however, the site of functionalization strongly depends on the structure of the steroid and the functional group.16-18 e.g. formation of 2. 

Trifluoromethyl hypofluorite reacts with various sulfides in trichlorofluoromethane at — 78 C forming difluoro- 624 and tctrafluorosulfancs 7,25 while fluorodesulfuration is observed in the reaction of amino acids, e.g. formation of 8.26 In a similar manner, trivalent phosphorus compounds react with trifluoromethyl hypofluorite to give difluoro-substituted derivatives 9.27... 

Barton and co-workers have studied30 the reactions of trifluoromethyl hypofluorite with various alkenes and found that (Z)- and (T -stilbene give vicinal fluoro trifluoromclhoxy products and vicinal difluorides in chlorotrifluoromethane or diethyl ether, while vicinal fluoro methoxy adducts predominate when the reaction is carried out in methanol at —78 C. svn Addition predominates in all cases on the basis of the fluorination regioselectivity of many alkenes, the formation of a /1-fluoro carbcnium ion is proposed.30... 

Perfluoro-tert-butyl hypofluorite [perfluoro(2-fluoroxy-2-methylpropane), 14], readily prepared by the low-temperature fluorination of potassium or sodium perfluoro-/cr/-butoxide,812 reacts with hexafluoropropenc at low temperature to give 15 with more than 95 % regiosclcctivity, which may be explained by electrophilic attack and the formation of a fluorocarbeniuni ion, whose intervention is suggested in order to explain the production of perfluoro(l-/m-butoxy-propane) (15).12... 

Reaction of aromatic molecules with methyl hypofluorite results in the formation of the methoxy products, e. g. 1,2,4,5-tetramethylbenzene (durene) gives methoxydurene in 90 % yield, and hexamethylbenzene provides the mono- (23) and dibenzylic (24) products. 9... 

Low-temperature fluorination of sodium acetate in suspension gives a mixture of acetyl hypo-fluorite (AcOF, 1, R = Me) and alkyl hypofluorite the crude mixture can be used, in some cases, directly for the introduction of fluorine into organic molecules. The course of the reaction strongly depends on the reaction conditions and, when the fluoride anion is quenched with hydrogen fluoride or water, trifluoroacetyl hypofluorite (1, R = CF3), 3 acetyl hypofluorite (1, R = Me) and long-chain acid fluorites are obtained.4-6 On the other hand, an excess of fluorine can lead to the formation of alkyl fluoroxy compounds 2 or geminal bis(fluoroxy) products 3. 

Enol acetates, oxo esters, nilroalkenes33 and sodium salts of various esters have been successfully converted into fluoro ketones and esters by acetyl hypofluorite, trifluoroacetyl hypofluorite or mixtures containing acetyl hypofluorite and fluoroxy compounds.3 4 -10-12-13 Examples are the formation of l-fluoro-l,3-diphenylacetone (12), a-fluoro-/i-oxo esters 13, a-fluoro ketones 14 and 15. ethyl l-fluoro-2-oxocyclopentanecarboxylate (16), and 2-fluoromalonate 17. 

Bicyclomycin rearrangement product, synthesis, 57, 224 2,2 -Bifuran, 5,5 -dibromo-, 57, 306 2,2 -Biimidazoles bromination, 57, 350 chlorination, 57, 347 2,2 -Biindolyl, synthesis, 56, 174 l,l -Biisoquinoline. formation from isoquinoline and LDA, 56, 245 fiimanes, fluorination by acetyl hypofluorite, 59, 4 Biological properties of heterocyclic betaines and precursors, 60, 250-1... 

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... 

Acetyl hypofluorite will only fluorinate activated aromatic compounds and fluorinations arc generally performed at low temperatures. In general a mixture of products is formed, for example, the fluorination of anisole with acetyl hypofluorite results in a mixture of 2-fliioroanisole and 4-fluoroanisole (ratio 9.6 1) in 85% yield (Table 11). This preferential formation of the ortho-Komcr is explained by an addition-elimination mechanism with an intermediate 15. This mechanism is support by the fact that the addition product 16 from acetyl hypofluorite and pipcronal is isolated in 55 % yield. Selective fluorination is achieved when the para position is blocked by a second substituent (Table 12). This approach has been used to selectively fluorinate an aromatic ring in peptide 17. " ... 

Table 33 summarizes some examples of the addition of trifluoromethyl hypofluorite to alkenes further examples are given by the formation of 3" and 4. ... 

The addition of trifluoromethyl hypofluorite to steroid double bonds has been investigated mainly by Barton and co-workers.3s6,406.4i 4.415.445 examples of these reactions are given by the formation of 5,383-385 g 3S3-385.406 384.386... 

Hypofluorites are also formed by similar catalytic formation of perfluoroalkoxide ions from the corresponding oxiranes (Figure 8.38). 

Initial attempts at the direct fluorination of carbonyl compounds such as acetone,72 butane-one,73 and butyric acid74 with elemental fluorine resulted in the formation of complex mixtures, with only low yields of a-monofluorinated carbonyl compounds formed. However, more recently, methyl 3-phenylpyruvate.75,7<1 and other pyruvate derivatives, e.g. I,77 are reported to be selectively monofluorinated with dilute elemental fluorine at — 10"C in moderate yield. The success of this reaction is attributed to the fact that the substrate predominantly exists in the enol form and not the keto form.77 Direct fluorination of acyclic 1,3-dicarbonyl compounds in formic acid or acetonitrile at room temperatures results in the formation of 2-fluoro-1,3-dicarbonyl compounds in good to excellent yield.78,79 Although in these systems the keto form predominates, there are significant concentrations of the enol form which undergoes fluorination (Table 5).78,79 The fluorination of 1,3-dicarbonyl compounds with acetyl hypo-fluorite is only successful when there are significant concentrations of the enol form compounds which have low concentrations of the enol form are successfully fluorinated by preparation of their metal cnolates followed by fluorination with acetyl hypofluorite (see Section 1.1.2.5.).95... 

Although thionyl tetrafluoride and pentafluorosulfur hypofluorite can be prepared by fluorination in a flow reactor, the procedures described here are performed in a static system. This method offers several advantages. The metal equipment needed is commercially available, and the ability to closely control the stoichiometry of the reactions results in the formation of the products in high purity. However, the amount of material that can be prepared in one run is limited. Thionyl tetrafluoride may also be prepared in good yield by the oxidation of sulfur tetrafluoride. This method is also easy to carry out if the requisite high-pressure equipment is available. 

Although the procedure described utilizes metal vessels for ease of treating the cesium fluoride and to avoid the formation of large amounts of silicon tetrafluoride, glass may be used. This procedure has been used for preparation of up to 0.015 mole of CF2(0F)2 at a time with the aid of liquid nitrogen to condense excess fluorine into the vessel. The method is analogous to that used in the preparation of pentafluorosulfur hypofluorite by the static, catalytic fluorination of thionyl fluoride in the presence of cesium fluoride. ... 

---