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

缩醛手性氧鎓离子不对称合成的研究进展及应用

基本信息

批准号：
12672054
负责人：
FUJIOKA Hiromichi
金额：
$ 2.5万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

已经在两个方向上研究了由甲乙烯的分子内孤立化形成的手性氧洋离子的不对称合成的开发和应用。在MeOH存在下，NBS进行了立体选择，通过歧视两个烯烃，通过抗MeOH进行了醛苯基乙酰乙酰基和（R，R） - 氢苯并素。进一步的转换进行了立体选择性进行，为了通过乙酰座的构象固定，形成了三个新的不对称中心，导致该化合物具有与Stenine碳骨架相同的构型。因此，获得的化合物被转化为9A-EPI-静脉。2）中二醇的不对称去对称：光学上纯的2-脱甲基 - 甲基-3-苯基-5Norbornen-5norbornen-2-氯烯-2-羧甲醛是通过我们的动力学控制的光学分辨率方法获得的。使用这种辅助，以四步骤的序列以高度对映选择性的方式实现了4-二醇：1）用二醇醛，2）在MeOH的存在下，在酸性水解的情况下进行了分子内溴醚化，然后在酸性水解的情况下进行3）乙烯，3）对结果进行保护。该方法应用于中氧和1,3-二醇，并观察到类似的高对映选择性。