Development and Application of the Asymmetric Synthesis Using Chiral Oxonium Ion Species from Acetals

本文从两个方面研究了烯烃缩醛分子内卤代醚化反应生成的手性氧离子不对称合成的发展和应用：1、多手性中心立体选择性的构建；2)球茎生物碱的合成研究：以甲基-2，5-二烯基甲基醛二乙缩醛和(R，R)-氢安息香合成的烯类缩醛为原料，在甲醇存在下，NBS进行分子内溴醚化反应，得到环己烯缩醛。进一步的转变是立体选择性地进行的，目的是为了构象固定缩醛，形成三个新的不对称中心，导致化合物具有与狭义碳骨架相同的构型。2)介孔二醇的不对称去对称化反应：我们的动力学控制光学拆分方法得到了光学纯的2-exo-methyl-3-endo-phenyl-5norbornene-2-carboxaldehyde。使用该助剂，以高对映选择性的方式实现了Meso-1，4-二醇的不对称反应，反应分四步进行：1)醛与二醇的缩合反应，2)在甲醇存在下的分子内溴醚反应，然后进行酸水解，3)保护生成的醇，4)脱溴醚反应。将该方法应用于Meso-1，2-和1，3-二醇，也观察到类似的高对映体选择性。

Development and application of the asymmetric synthesis using chiral oxonium Ions formed by an intramolecular haloetherification of ene acetals have been studied in two directions, 1 and 2.1) Stereoselective construction of multi-chiral centers Synthetic study of stemona alkaloids : An intramolecular bromoetherification of the ene acetal, prepared fromeyelohexa-2, 5-dienyl methyl aldehyde diethyl acetal and (R,R)-hydrobenzoin, by NBS in the presence of MeOH proceeded stereoselectively to give the cyclohexene acetal by discrimination of the two olefins. Further transformations proceeded stereoselectively for the sake of conformational fixation by the acetal to form the three new asymmetric centers leading to the compound having the same configuration as stenine carbon skeleton. Thus obtained compound was converted to 9a-epi-stenine.2) Asymmetric desymmetrization of meso-diols : Optically pure 2-exo-methyl-3-endo-phenyl-5norbornene-2-carboxaldehyde was obtained by our kinetically controlled optical resolution method. Using this auxiliary, deasymmetrization of meso-1, 4-diols was achieved in a highly enantioselective manner in a four step sequence : 1) acetalization of an aldehyde with a diol, 2) an intramolecular bromoetherification in the presence of MeOH followed by acid hydrolysis, 3) protection of the resulting alcohol, and 4) debromoetherification. The method was applied to meso-1,2- and 1,3-diols, and similar high enantioselectivity was observed.