V-Fluoropyridinium salts

The stability of hypofluorites is improved in derivatives having electron-withdrawing substituents, such as 2,2-dichloropropanoyl hypofluorite.48 Various other fluorinating agents have been developed and used, including /V-fluoropyridinium salts such as the... 

The effects of ring substituents and counterions on the preparation and reactivity of the /V-fluoropyridinium salts have been repotted in detail [74, 75, 76]. 

Various steroid-derived enamines (e.g 14) have been fluorinated with either V-fluoropyridini-um trifluoromethanesulfonate (11a) or A -fluoro-2,4,6-trimethylpyridiniiim trifluoromethane-sulfonate (11b). A study of these fliiorination reactions indicated that the yield of fluorinated compound is directly related to the electronic nature of the amine substructure. Thus, the yield is higher when less basic cnamino derivatives are used, according to the order morpholino > piperidine > pyrrolidin-l-yl. Moreover, the milder V-fluoropyridinium salt 11b gives better yields than salt 11a. 

Safe conditions for a direct fluorination of substituted pyridines with molecular fluorine have been found, but the method is of little synthetic value considering the large amounts of pyridines required (87TL255). Various 2-fluoropyridines can conveniently be prepared by base-induced decomposition of /V-fluoropyridinium salts with the unsubstituted 2/6 posi-... 

Dicarbonyl compounds are selectively fluorinated a to the two carbonyl groups with 1-fluoro-4.6-bis(trifluoromethyl)pyridinium 2-sulfonate (2) at room temperature. In sharp contrast, the fluorination of carbonyl compounds with l-fluoro-2,4,6-trimethylpyridinium trifluoro-methanesulfonate (3) requires heating and Lewis acid catalysis (Table 6). The reactivity of the pyridinium N-F reagent is dependent on the electronic nature of the substituents on the ring.41 When two equivalents of. V-fluoropyridinium salts were used for the fluorination of 1,3-dicarbonyl compounds, the major product was the 2,2-difluoro derivate (Table 7). 

Umemoto, T. Tomizawa, G. Preparation of 2-fluoropyridines via base-induced decomposition of V-fluoropyridinium salt. J. Org. Chem. 1989, 54(7),1726-1731. 

Even poor nucleophiles such as the amides 46 can react with azines in the presence of alkynes as activating agents [59, 60]. Various nucleophiles (including alkoxides, thiols, amines and nitrogen heterocycles) were recently employed in a related process with Ai-oxide azaindoles (Reissert-Henze reaction. Scheme 10). In the process, the oxygen is alkylated with dimethyl sulfate and, after the nucleophilic attack, methanol is released to aromatize the initial adduct [61,62]. Following similar mechanistic trends, V-heteroatom-activated azines afford the corresponding substituted adducts. Likewise, W-tosylated isoquinoline [63, 64] and W-fluoropyridinium salts [65] are also reactive substrates in Reissert-Henze type processes. 

Reagents i, H2-Pd ii, HN03-AcCH iii, KOH iv, H+ v, LiAlH4 vi,BuaLi vii, TiCl4-LiAlH4 viii, l-methyl-2-fluoropyridinium salts... 

The fluorination of carbonyl compounds is facilitated by the formation of a metal enolate prior to fluorination. The fluorination of metal enolates has been successfully achieved using a wide variety of N-F reagents, e.g. A-fluorosulfonamidcs, chiral /V-fluorocamphorsul-tam." A-fluorooxathiazinone dioxides," iV-fluoroperfluoroalkylsulfonamides." 1-fluoropyridinium trifluoromethanesulfonates, " and l-alkyl-4-fluoro-1,4-dia7-oniabicyclo[2.2.2]octane salts" (see Table 8). 

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