Synthesis of Biologically Active Perfluoroalkyl N-Heterocycles Using Organosilicon Reagents

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Five 2-aryl-3-(3-methyl-5-isoxazolyl)-N-silyl-1-aza-allyl anions (1) (Ar = C_6H_5, pーCH_3C_6H_4, p-CH_3OC_6H_4, p-CIC_6H_4, p-N(CH_3) _2C_6H_4), generated from 3-methyl-5-(trimethylsilylmethyl) isoxazole and the corresponding aryl cyanides, reacted with perfluoro (2-methyl-2-pentene) (2) in the presence of Hunig's base in tetrahydrofuran at low temperature to give the corresponding 6-aryl-2-fluoro-5-(3-methyl-5-isoxazolyl)-4-pentafluoroethyl-3-trifluoromethylpyridines (3) in high yields (97, 74, 52, 80, 93%, respectively) under the optimized reaction conditions. Further-more, the isoxazole ring of the pyridine (3) was quantitatively hydrogenated to afford the corresponding bata-amion enone (4), which was intramolecularly cyclized to give 5-ary1-7-fluoro-2-methyl-8-trifluoromethyl-1, 4-dihydro-1, 6-naphthyridine (5) in good yields (Ar = C_6H_5, p-CIC_6H_5, yield = 63, 67%, respectively) in the presence of sodium hydroxide at room temperature. The mechanisms for these two reaction were also discussed on the basis of the reactivity of (3) against sodium hydroxide or alkylamines.alpha-(Trimethylsilylmethyl)-N-heterocycles, such as pyridine, quinoline, and isoquinoline, reacted with (2) in the presence of fluoride anion to afford Rf-substituted quinolizin-4-ones (or the corresponding benzo derivatives) in poor to good yields through intermolecular addition-cyclization reaction.