One-Pot Synthesis of Perfluoroalkylated 4-Fluoropyridines via N-Sily1-1-azaally1 Anion

Abstract

An N-silyl-1-azaallyl anion [3 a], generated from an α-silyl carbanion [1a] of 3-methy1-5(trimethylsilylmethypisoxazole and benzonitrile [2 a], reacted with an excess amount of perfluoro(2-methyl-2-pentene) [5 ] in the presence of various kinds tertiary amines i n tetrahydrofuran to give 4-fluoro-5-(3-methy1-5-isoxazoly1)-2-pentafluoroethyl-6-phenyl-3(trifluoromethyppyridine [6 a]. Under the reaction conditions determined as optimum, the corresponding five pyridines [6 a]-[6 e] were prepared from the anion [1 a] and p-substituted benzonitriles [2 a] -[2 e] [Ar=C₆H₅, p-CH₃, C₆, H₄, p-CH₃OC₆H₄, p-C1C₆H₄, p-(CH₃)2NC₆H₄]in good yields (67, 48, 70, 51 and 56%, respectively). The reaction was extremely accelerated by the trimethylsilyl group of the anions [3]. However, an analogous reaction of the anion [1 b], derived from 2-(trimethylsilylmethyl)pyridine, did not give the 4-fluoropyridine derivative [6 f], but gave the corresponding 4-pyridone [8 f] in poor yield (22%).