Fluorinated Hypofluorites and

J. M. Shreeve, Fluorinated Hypofluorites and Hypochlorites, Advan. Inorg. Chem. Radiochem. 26 [1983] 119/68, 121/3. 

One may conclude that the above-mentioned anhydrous [ F]fluorine compounds, except perhaps H[ F]F, have been abandoned, partly because of their limited potential and difficulty of preparation and also because of the success of the main three agents of today, [ F]fluoride (see Section 4), p F]fluorine gas (see Section 3.1.1) and acetyl [ F]hypofluorite (see Section 3.1.3). The advent of the first one, ([ F]fluoride), made less urgent the need for high-specific-activity electrophilic fluorine and the latter two, ([ F]fluorine gas and acetyl p F]hypo-fluorite), are able to perform practically all low-specific-activity electrophilic syntheses (see Section 3), putting a brake on the development of alternatives. 

As has been exemplified in this chapter, fluorinations with fluorine-18 can be classified into two categories (1) the nucleophilic reactions, which usually involve no-carrier-added [ F]fluoride of high-specific radioactivity as its Kf FIF-K complex and include substitutions in the aliphatic and the /lomoaromatic series and (2) the electrophilic reactions, which mainly use moderately low-specific radioactivity molecular [ F]fluorine, or other reagents prepared from it, such as acetyl [ F] hypofluorite, and include addition across double bonds, reactions with carbanions and especially fluorodehydrogenation and fluorodemetallation reactions. 

Trifluoromethyl hypofluorite was first made by Cady by passing methanol [184] or carbon monoxide [185, 186] with fluorine over silver difluoride at elevated temperatures. Later, trifluoromethyl hypofluorite and higher perfluoroalkyl hypofluorites were prepared by treating the appropriate carbonyl compound with fluorine in the presence of dry caesium fluoride at sub-zero temperatures (Fig. 81) [187-189]. 

When fluorine is passed through a mixture of methanol in acetonitrile at -45 °C or propionitrile at -75 °C a solution of methyl hypofluorite, stabilised by the solvent, is produced [200]. While methyl hypofluorite can be isolated, its chemistry has been investigated by treating various substrates with freshly prepared solutions rather than with isolated material. Unlike the hypofluorites which have been discussed so far, methyl hypofluorite behaves as a synthon for the rare methoxylium species, MeO+ , and adds to various alkenes electrophilically in accordance with Markovnikov s Rule [201]. In the reaction between methyl hypofluorite and indene, almost exclusive trans addition occurred. 

In this section we will discuss the use of elemental fluorine for the promotion of organic transformations that do not result in the introduction of fluorine into the substrate. As we described above (Sect. 3), fluorine may be used to prepare many extremely useful reagents which may be employed as, for example, oxidising and oxygen transfer agents. The use of O-F compounds, such as acetyl hypofluorite and the HOF.MeCN complex, in functionalisation processes has been indicated above (Sect. 3.2), and this area has been discussed in detail in an excellent account by Rozen [19]. 

C1F 54.46 - 155.6/- 100.1 + + + + also usable for synthesis of hypofluorites and oxidative S- or Se-fluorinations of organic sulfur and selenium compounds, frequently in situ preparation of the agent from A -chloro-substituted amides and HF, HF-containing systems or AgF 4, 7... 

Various steroids can be fluorinated, to provide vicinal fluoro acetates with predominant or exclusive syn addition, with acetyl hypofluorite or a mixture of acetyl hypofluorite and fluoroxy compounds,4"10 e.g. reaction of 18 and 19. 

Various uracil, cytosine and pyrimidine nucleosides, e.g. 22, have been successfully fluorinated by acetyl hypofluorite and also some labeled I8F derivatives synthesized.16- 18 34... 

The fact that functionalization of polymers and small molecules is observed to occur predominately on terminal (methyl) carbon atoms does not imply that the oxyfluorination reaction is truly selective. Although the reaction mechanism has not been studied in detail, it is undoubtedly a free-radical process. Molecular oxygen reacts spontaneously with the fluorocarbon—hydrogen radicals generated by fluorine during the fluorination process. Acid fluorides are retained on terminal carbon atoms because they are stable in 1 atm of elemental fluorine. Hypofluorites, which may be short-lived intermediates of oxygen reactions with methylene radical sites along the carbon chain, are not observed in the functionalized polymers. It is probable that, if they are intermediates, they are cleaved and removed by the excess elemental fluorine. 

The aryl tin compounds are better substrates for fluorination because they give high yields of fluorinated aromatics and they may be fluorinated with acetyl hypofluorite, cesium fluoroxysulfate, or fluorine [52, 54 (equation 28). Aryl boronic esters react with cesium fluoroxysulfate to produce fluoroaromatics [55] (equation 29). 

Progress in the preparation and isolation of different hypohaiites [92] results in a substantial number of publications exploring the addition of these materials to fluoroolefins. In contrast to addition of hypofluorites, which at this time is viewed as a radical process, a polar mechanism was proposed for addition of poly-fluorinated hypochlorites and hypobromites to olefins. Reactions of fluoroolefins... 

The substitution of hydrogen atoms by fluorine in aromatic compounds has been investigated with many classes of reagent, including elemental fluorine. hypofluorites, " fluoroxysulfates. xenon difluoride," and N-F reagents. " ... 

Aromatic systems arc fluorinated by reagents containing an O-F bond, in particular by tri-fluoromethyl hypofluorite, and acetyl hypofluoritc. Trifluoromethyl hypofluorite is a commercial reagent which is prepared by the reaction of elemental fluorine with carbon monoxide. The initial product is carbonyl fluoride 10 formed by a spontaneous and highly exothermic reaction. This product is passed through a bed of cesium fluoride which catalyzes the addition of a second mole of fluorine to give trifluoromethyl 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. " ... 

Fluorination of aryltrimethylsilanes with xenon difluoride is a method for the synthesis of F-labelcd eompounds, since [ F]XeF2 be prepared. F-Labeled aryl fluorides are also prepared by reaction of aryltrimethylsilanes with F-labeled acetyl hypofluorite and elemental fluorine. ... 

Xenon difluoride, the most easily handled of the xenon fluorides, was first prepared by a complicated, low-pressure, ultraviolet-irradiated reaction between xenon and fluorine. Hypofluorites have been used to produce the difluoride from xenon by means... 

Nonfluorinated alkyl hypofluorites (ROF) are mostly unstable and decompose through HF elimination with formation of the corresponding carbonyl compounds. However, tert-butyl [24] and methyl hypofluorites (RO+ F ) [25] can be generated and employed in situ for alkoxy-fluorination of alkenes. The relatively higher stability of both hypofluorites comes from the nonavailability of a-hydrogens which are reactive to the radical hydrogen abstraction [26]. Both of the hypofluorites add to carbon-carbon double bonds regio- and stereoselectively as shown in Scheme 2.48. The anti-addition mode (37-39) is in sharp contrast to the syn-addition mode of electrophilic fluoroalkoxy and acetoxy reactions of fluorinated alkyl and acetyl hypofluorites (RfO F+, 40-41) [27]. 

---