N-Fluoropyridinium salts

A novel route to 2-fluoropyridines involved the base-induced decomposition of substituted N-fluoropyridinium salts. Abstraction of the 2-H produces a singlet carbene (11) that removes F from a counterion. This is in contrast to the reaction with C nucleophiles, which are fluorinated, and is attributed to the high stability of C—F compared to O—F and N—F (89JOC1726). 

Meinert demonstrated that fluorination of pyridine at low temperatures gives the ionic salt N-fluoropyridinium fluoride, a compound that was reported to be explosive at 0°C (Fig. 59) [154]. However, direct fluorination of variously substituted pyridines is possible and good yields of the corresponding 2-fluoro-pyridines (Figs. 60 and 61) [155] are obtained, offering an attractive alternative to the usual halogen-exchange and Balz-Schiemann routes to these products. These reactions probably proceed via N-fluoropyridinium salts (Fig. 62) which are activated towards nucleophilic attack. 

Although a number of electrophilic fluorinating reagents are known, most are toxic, unstable, and difficult to handle. These new, stable N-fluoropyridinium salts are readily obtained in 60-80% yield by reaction of a pyridine with F2/N2(l/9) in CH3CN in the presence of sodium triflate. 

Oxidation of pyridinecarboxylic acids.1 Reaction of a pyridinecarboxylic acid or the ester with 10% F2 in N2 results in oxidation to the corresponding 2-pyridone in 50-75% yield. An N-fluoropyridinium salt is probably an intermediate. 

With the increasing importance of organofluorine compounds in the development of new materials, pharmaceuticals, and agricultural chemicals, N-fluoropyridinium salts should find extensive use as mild and selective fluorinating agents. 

Due to these safety problems, the search for new, easy-to-handle electrophilic fluorinating agents has become an important area of research. Some of these new reagents have been tested in the fluorination of enamines to give a-fluoro ketones. These include l-fluoropyridin-2(l//)-one (9),116 N-fluoroquinuclidinium fluoride (NFQNF, 10),117 N-fluoropyridinium salts 11,118 and N-fluorobis(trifluoromethanesulfonyl)aminc (Tf2NF. 12).42... 

Enol alkyl ethers, enol silyl ethers, vinyl esters, and enamines undergo reactions with N-fluoropyridinium salts to give a-fluoroketones, as illus-... 

Some nucleophiles add to Af-fluoropyridinium salts to give dihydropyridines in which elimination of fluoride occurs in situ to give the 2-substituted pyridine, thus avoiding the need for a dehydrogenation step. The main disadvantages of this method are that the preparation of the pyridinium salts require the use of elemental fluorine and that some carbanions give only modest yields due to competitive reactions such as C-fluorination. However, silyl enol ethers do react efficiently stabilised heteronucleophiles (phenolate, azide) can also be used. Addition to N-fluoropyridinium salts shows a strong preference for attack at an a-position. ... 

Chemical fluorination of the types of compounds mentioned above was also examined using commercially available fluorinating reagents such as N-fluoropyridinium salts and EtjNSFj (DAST) as these reagents are known to be effective for fluorinations of sulfides. However, the use of these reagents did not give rise to formation of any of the desired fluorination products in most cases or to only low yields of these materials. Therefore, electrochemical fluorination is superior to the conventional chemical fluorination methodologies. 

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