Trifluoromethyl hypofluorite fluorination using

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... 

Styrene and 1,1-diphenylethene are frequently used as target molecules in investigations of the role of reagent structure on its reactivity toward organic compounds. Low-temperature fluorination with trifluoromethyl hypofluorite gives up to six products.32-33 The Hammett correlation value q was established to be — 2.48 and a mechanism suggested in which spin-paired free-radical pairs arc formed, which are then converted by electron transfer into an ion pair.33... 

Depending on the fluorinating reagent used, the reaction of imines leads to different fluorination products. Treatment of Schiff bases with trifluoromethyl hypofluorite gives A,A-difluoro amines under mild reaction conditions however, if the reaction is carried out using A-fluoro-bis(trifluoromethanesulfonyl)amine (TfjNF), a-monofluoro 2 and/or a,a-difluoro ketones 3 are obtained (Table 11). ... 

Trifluoromethyl hypofluorite, CF3OF, the first organic hypofluorite, reacts as if the O-F bond is homolyzed to the trifluoromethoxy radical and a fluorine radical in many reactions, but it has been used effectively as a selective electrophilic fluorination reagent in organic chemistry. It has limited selectivity as a fluorination reagent in inorganic chemistry bnt it can be oxidatively added to numerous compounds. 

Trifluoromethyl hypofluorite, CF3OF, is formed by the reaction of fluorine in excess with carbon monoxide, carbon dioxide, methanol, or other compounds containing both carbon and oxygen. In the procedure described below, carbon monoxide first reacts with an excess of fluorine to give largely carbonyl fluoride. The mixture is then passed through a hot tube where nearly all of the carbonyl fluoride reacts with fluorine to give trifluoromethyl hypofluorite. It is desirable to use somewhat more than two volumes of fluorine per volume of carbon monoxide. If this is not done, much perfluorodimethyl peroxide [bis(trifluoromethyl) peroxide] is formed by the combination of carbonyl fluoride with tr fluoromethyl hypofluorite by the reaction ... 

Other powerful fluorinating agents, such as trifluoromethyl hypofluorite, perchloryl fluoride and acetyl hypofluorite (CF3OF, FCIO3, AcOF) have been used successfully, but are not easy to obtain, are toxic and the last two are intrinsically explosive. Some newer, milder, but more limited, fluorinating agents are discussed later in this section. 

Molecular parameters for trifluoromethyl hypofluorite, determined by electron diffraction," are available and interest in this compound and others of its class as electrophilic fluorinating agents is widening. For example, the trifluoromethyl compound itself has been used to obtain directly 5-fluoro-uracil bases and 5-fluorocytosine and related nucleosides," -" to convert... 

The use of fluorine, a pyridine-fluorine complex, or trifluoromethyl hypofluorite for the preparation of 5-fluorouracil and related compounds has already been mentioned (see p. 262, particularly ref. 357). Electrochemical fluorination (Simons process) of uracil also gives 5-fluorouracil, > and trifluoromethyl hypofluorite has been applied to the preparation of l-(tetra-hydro-2-furanyl)-5-fluorouracil (Ftorafur) (Scheme 49), which is claimed to have a greater activity towards cancer of the breast and the gastrointestinal tract than 5-fluorouracil, while being considerably less toxic. 6-Fluoro-thyamine (245) has been prepared from 2,4,6-trifluoro-5-methylpyrimidine... 

Several reagents were used for the electrophilic fluorination of indole. The first one used for this aim was trifluoromethyl hypofluorite (CF3OF). Treatment of V-acylindole 1 with trifluoromethyl hypofluorite in CF3CI at -78 °C afforded a mixture of 2-fluoro-3-trifluoromethoxy- and 2,3-difluoroindoline derivatives 2-4 in high combined yield. Subsequent treatment of difluoride 4 with potassium hydroxide in methanol afforded quantitatively 3-fluoroindole 5. Similarly, starting from l-formyl-2-methylindole reaction with trifluoromethyl hypofluorite resulted in formation of 2-methyl-3-fluoroindole 7 in low yield in mixture with 2-methyl-3-trifluormethoxyindole 8 [7]. 

Other addition/elimination sequence was utilized for monofluorination of benzofuran and its derivatives. Thus, the reaction of benzofuran 11 with trifluoromethyl hypofluorite (CF3OF) furnished 2-fluoro-3-trifluoromethoxy-2,3-dihydrobenzofurans 16 (43 % cis- and 15 % franx-isomer) and dx-difluoroderivative 17 (19 %). Treatment of the derivative 17 with ethanohc potassium hydroxide produced 3-fluorobenzofuran 18 in 61 % yield [20], 3-Fluorobenzofuran 18 was also synthesized from the compound 19 using silver fluoride as fluorinating and dehydrohalogenating reagent at the second step [21],... 

Robins MJ, MacCoss M, Naik SR, Ramani G (1976) Nucleic acid related compounds. 21. Direct fluorination of uracil and cytosine bases and nucleosides using trifluoromethyl hypofluorite. Mechanism, stereochemistry, and synthetic applications. J Am Chem Soc 98 7381-7389... 

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