Nucleophilic Fluorination of 3-Cyanopyridines

Significance

This paper describes the synthesis of 3-cyano-2-fluoropyridines by nucleophilic substitution of 2-nucleofuge-containing substituted 3-cyanopyridines. This method employs classic sources of nucleophilic fluoride such as KF and Bu₄NF in DMF or DMSO at high temperatures. The use of chloride and bromide 2-nucleofuges affords 3-cyano-2-fluoropyridines in moderate to good yields as shown. The 2-bromo starting materials present the advantage of being synthesized in one step in good yields, contrary to the 2-chloro-3-­cyanopyridines which are prepared in moderate yields. Readily available 3-cyanopyridine-2(1H)-thiones have also been C2-fluorinated in good yields via 3-cyano-2-methanesulfonylpyridines and tetrahydrothiophenium salt intermediates.