A Novel Synthesis of Biologically Active Perfluoroalkyl N-Heterocyclic Compounds Using Organosilicon Reagents

由3-甲基-5-(三甲基硅甲基)-异恶唑和芳基氰化物生成的N-硅基-L-氮烯丙基阴离子(1)与全氟(2-甲基-2-戊烷)(2)或3-乙酰基-4-甲氧基-3-丁烯-2-酮(3)高产率地反应得到相应的RF或4-Me吡啶(4)或(5)。在氢氧化钠存在下，通过异恶唑环的氢化和连续的分子内环化反应，前一种产物(4)以较高的产率有效地转化为相应的1，6-萘啶。另一方面，在氟化钾存在下，2-(三甲基硅甲基)吡啶与(2)反应生成2-pentafluoroethyl-3-trifluoromethyl-4H-quinolizin-4-one(6)。甲基吡啶、甲基喹啉、苯并恶唑和苯并噻唑的硅基衍生物发生类似反应，以较高的产率得到相应的RF取代化合物。此外，化合物(6)经硫酸处理后，高产率地得到了(6)的3-羧酸甲酯，(6)经硫酸处理后经水解脱羧基定量得到了2-五氟乙基-4H-喹啉-4-酮(7)。并对这些反应的机理进行了讨论。

N-Silyl-l-aza-allyl anions (1), generated from 3-methyl-5-(trimethylsilylmethyl)-isoxazole and aryl cyanides, reacted with perfluoro(2-methyl-2-pentane) (2) or 3-acethyl-4-methoxy-3-buten-2-one (3) to give the corresponding Rf or 4-Me pyridines (4) or (5) in high yields. The former product (4) was effectively converted into the corresponding 1,6-naphthyridine in good yield by hydrogenation of the isoxazole ring and the consecutive intramolecular cyclization in the presence of sodium hydoxide. On the other hand, 2-(Trimethylsilylmethyl)pyridine reacted with (2) in the presence of potassium fluoride to afford 2-pentafluoroethyl-3-trifluoromethyl-4H-quinolizin-4-one (6) in quantitative yield. The analogous reaction of the silyl derivatives of methylpyridines, methylquinolines, benzoxazole and benzothiazole gave the corresponding Rf-substituted compounds in good yields. The compound (6), furthermore, gave the methyl ester of the 3-carboxylic acid of (6) in high yield on treating with dimethyl sulfate whereas (6) quantitatively gave 2-pentafluoroethyl-4H-quinolizin-4-one (7) by decarboxylation after hydrolysis on treating with sulfuric acid. The mechanisms of these reactions were also discussed.