Hypofluorites reactions with

Acetyl hypofluorite gas is used in a reaction with an arylmercunc acetate to produce a derivative of L-DOPA [56] (equauon 30). 

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. ... 

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 is generally used at low temperatures with reactants dissolved in an inert solvent, but to increase the solubility of reactants a cosolvent (MeOH, acetone, THF) is often used however, it must be used with extra caution and appropriate safety precautions against explosions and fires, since trifluoromethyl hypofluorite is a powerful oxidizing agent. The toxicity of trifluoromethyl hypofluorite is expected to be high (as with fluorine). Fluori-nation reactions with trifluoromethyl hypofluorite have been discussed in the last twenty years in review papers6 11,65 and several monographs.12" 14... 

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... 

When ketones, aldehydes and esters are transformed to silyl enol ethers, further reaction with trifluoromethyl hypofluorite gives a-fluoro carbonyl products 16 in good to excellent yield.31... 

Benzene (32, R = H) reacts under photochemical conditions with trifluoromethyl hypofluorite giving fluorobenzene as the main product together with (trifluoromethoxy)benzene,15 while the reaction with toluene (32, R = Me) also gives sidc-chain-substituted products.2,3,15... 

The reactivity of aromatic molecules in fluorination reactions with trifluoromethyl hypofluorite has been studied in detail, and in the case of aniline derivatives the effect of the substituent on nitrogen on the relative reactivity and ortho/para ratio in various aprotic nonpolar, aprotic polar and protic solvents has been determined.5... 

Trifluoroacetyl hypofluorite is the main product in the low-temperature fluorination of sodium trifluoroacetate in suspension in an inert solvent, and can be further transformed to pentafluoro-(fluoroxy)ethane.2 In some cases, the reaction mixture of up to four reactive products [fluoroxy, bis(fluoroxy) and acyl hypofluorites], formed in reactions with various acid salts, c.g. 5, has been directly used for the fluorination of organic molecules.1 " 5... 

In the reaction with hexafluorobenzene at 40"C exclusive 1,4-addition to give 18 is observed. In addition to higher regioselectivity, perfluoro-fcrf-butyl hypofluorite has higher reactivity as a reagent compared to trifluoromethyl hypofluorite (see Section 6.1.1.).14... 

Reactions with Methyl Hypofluorite and ferf-Butyi Hypofluorite... 

Acetyl hypofluorite appears to be a milder reagent than trifluoroacetyl hypofluorite in the fluorination of alkenes and acetylenes. Acetyl hypofluorite undergoes addition to the C = C bond in the fluorination of cyclohexene the ij f7-adduct 4 is obtained in 60% yield, while the reaction with dodec-l-ene gives 2-acctoxy-l-fluorododccanc (5) in 30% yield.10... 

Reactions with acetylenes have been much less intensively studied, but important and large differences between trifluoromethyl hypofluorite and trifluoroacetyl hypofluorite have been observed.2 An example of the reactivity of trifluoroacetyl hypofluorite with acetylenes is given by the reaction with 1,2-diphenylacetylene (23) acetyl hypofluorite is unreactive even at room temperature.10... 

Acetyl hypofluorite reacts with various activated aromatic molecules with a very high degree of ortho selectivity, e.g. reaction of 24, 25, and 26, which has been explained by an intermediary addition reaction followed by rearomatization. The addition products 27 may be isolated in the reaction with piperonal.10 20... 

Directed introduction of fluorine and the 18F isotope has been achieved by reactions of acetyl hypofluorite with tin or mercury derivatives 29 or 30, respectively.25 The course of the reaction with mercury derivatives depends on the structure of the substrate and as well as fluorinated products, acetates and toluenes are also formed.26-27... 

Vicinal fluoro methoxy compounds, e.g. 32 and 33, are regioselectively prepared in high yield from vicinal methoxy chloromercurio derivatives by reaction with acetyl hypofluorite.29... 

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. 

Trifluoromethyl hypofluorite gained its initial popularity, however, from its reactions with enol derivatives. Such reactions continued to be important during the last decade. The synthesis of complex molecules such as fluoroerythromycin (equation 137)244 and 2-fluoro (25)245 and 16-fluoroestradiols (26) (equation 138)246 are good examples of using CF3OF to produce compounds with useful therapeutic properties. 

Hexafluorobenzene and pentafluorotellurium hypofluorite produced, after four days at 25°, a 50% yield of hexafluorocyclo-hexa-2,5-dien-l-yloxy tellurium pentafluoride3. Similar reactions with pentafluorotellurium hypochlorite gave much lower yields of addition products2. 

Acetophenone, A/-methyloxazolidine derivative, lithiation, 56, 261 Acetyl hypofluorite fluorination of uracil by, 59, 3 fluorination using, 60, 7 reaction with pyridines, 58, 280, 289 Acetylacetone, hexafluoro-, reaction with ethylenediamine, 56, 3 Acetylene cyclic dimer, trimer. tetramer, dissociation energies, 56, 343 Acetylenes, activated reactions with 3-diazo-azoles, 59, 70... 

Fluoroaromatic compounds 8 are synthesized by reaction of aryltrialkyltin derivatives with electrophilic fiuorinating reagents, such as cesium fluoroxysulfate, trifluoromethyl hypo-fluorite and acetyl hypofluorite, or with elemental fluorine. In Table 4 examples of these reactions arc summarized. 

The reaction of alkenes with acetyl hypofluorite - or with fluorine, 2,3,4,5,6-pen tachloro-1 -fluoropyridinium trifluoromcthanesulfonate (Af-FPCPy-OTO, ... 

The electrophihc nature of COF2 is beneficial in the reaction of carbonyl difluoride with CsF, which produces trifluoromethyl hypofluorite (CF3OF) with fluorine and triflnoromethyl hypochlorite (CF3OCI) with chlorine monoflnoride. Both reactions imply the presence of the triflnoromethoxide anion as an intermediate. 

Evidence has been presented that hypofluorites (see Section IIIB) can act as sources of electrophilic fluorine for reactions with electron-rich double bonds [11, 93]. Syn addition usually occurs and a tight ion-pair intermediate similar to that postulated to occur in the direct fluorination of alkenes can be envisaged. However, electron-transfer processes have been invoked [93] to explain some anomalous results and cannot be discounted [281] (Figure 3.64). 

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