Electrophilic fluorinating agents, preparation

There are two types of hypofluorite compounds that have been prepared, the perfluoroalkyl hypofluorites, such as CF3OF, and the acyl hypofluorites, such as CH3C02F. The fluorines of such compounds are very deshielded and thus have significantly positive chemical shifts (Scheme 7.15). Also shown is the powerful electrophilic fluorinating agent, perchloryl fluoride. 

N , N -1 )ifluoro-2,2 -bipy ri < (i n i 11 rn bis(tetrafluoroborate) 19, prepared in one pot by introducing BF3 gas into 2,2 -bipyridine at 0°C followed by fluorine gas diluted with nitrogen, was shown to be a highly reactive electrophilic fluorinating agent (Equation 5) <2003JFC173>. 

Caesium fluoroxysulphate (CSSO4F) [94] is a solid electrophilic fluorinating agent that is very easily prepared [100] (Figure 3.14) but, unfortunately, is very prone to rapid uncontrolled decomposition. However, it has been used for the fluorination of hydrocarbons [101] and aromatics [102-104] (Figure 3.15). 

There is now available a range of stable, easily handled, solid electrophilic fluorinating agents of the N-F type. These remarkable reagents are generally prepared by reaction of a neutral base [108] or a salt [109] with fluorine (Figure 3.16). 

An early report described the preparation in low yield of two isomeric meso-monofluorinated derivatives of porphyrins using the Schiemann reaction. Electrophilic fluorinating agents have been a more effective way to carry out direct fluorination of the porphyrin system. For example, reaction of octaethylporphyrin with A-fluoropyridinium salts such as A-fluoro-2,3,4,5,6-pentachloropyridinium triflate gave a mixture of mono, di, tri, and tetrafluoro derivatives 88 (Fig. 3.41). The perfluorinated derivative was formed in 20% yield. mew-Fluorination of octaethylporphyrin had minimal effects on oxidation potential and spectral properties. 

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. 

Bromo [ F]fluoride is different from the other electrophilic radiolabelling agents discussed so far in the sense that the electrophilic part of the molecule is not fluorine but bromine. This is reflected by its synthesis from nucleophilic p F]fluoride and it can be obtained in high specific radioactivity. Bromo p F]fluoride was developed for fluorine-18 labelling of steroids (see Section 3.2) [64-66]. It was prepared (Scheme 11) in situ by reaction of dried p Fjfluoride with 1,3-dibromo-5,5-dimethylhydantoin and sulphuric acid in dichloromethane containing also the substrate. 

Several 2-fluoroerythromycin derivatives have also been prepared by means of electrophilic fluorination with Selectfluor of the enolate of the )S-ketoester fragment (Fig. 45) [121]. Fluorination is stereoselective and leads to the a-fluo-rine compound [122]. Two derivatives of 2-fluoroerythromycin are in clinical development HMR-3562 and HMR-3787). These compounds are promising agents for the treatment of respiratory pathogens resistant to erythromycin A (Fig. 45) [123]. 

One of the most convenient synthetic routes for the preparation of vinyl fluorides 2 is by treatment of the corresponding vinyltin compounds 1 with electrophilic fluorinating reagents. This procedure is also used for the preparation of aryl fluorides, since it is well-established that fluorination with electrophilic reagents is facilitated by ipso substitution of a suitable, usually weakly bonded, metal function. In the case of aryl fluorides, the reaction is also carried out using elemental fluorine as the fluorinating agent. ... 

---