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Asymmetric Synthesis based on Intramolecular Haloetherification of Ene Acetals and Its Application

基于烯缩醛分子内卤醚化的不对称合成及其应用

基本信息

批准号：
10671989
负责人：
FUJIOKA Hiromichi
金额：
$ 2.11万
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：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

In this project, we studied on asymmetric synthesis based on intramolecular haloetherification of ene acetals and its application in two ways : 1) asymmetric desymmetrization of σ-symmetric dienes-synthesis of multi-chiral center, and 2) asymmetric desymmetrization of symmetric diols.1) Asymmetric desymmetrization of σ-symmetric dienes-Synthesis of multi-chiral centers : An intramolecular haloetherification reaction, treatment with NBS in the presence of MeOH, of ene acetal, prepared from 2,5-cyclohexadiene-1-methylaldehyde and chiral hydrobenzoin, proceeded stereoselectively to give 8-membered acetal discriminated two olefins. Subsequent hydroboration of the remained olefin followed by oxidation afforded the cyclohexenone derivative. Stereoselective 1, 4-addition of Grignard reagent, silylation of enolated anion, excess MeLi treatment, then diallylation with excess allyl iodide afforded the compound with the same carbon skeleton of (-)-stenine, a major component of stemona alkaloids.2) Asymmetric desymmetrization of symmetric diols : An asymmetric desymmetrization of unsaturated cyclic and acyclic meso-1, 2-diols has been developed from the ene acetals, prepared from the norbornene carboxyaldehyde and unsaturated meso-1, 2-diols. The intramolecular haloetherification of the ene acetals as a key step afforded 8-memberd acetals in a stereoselective manner just by the reaction of norbornene olefin. Subsequent reductive elimination, followed by protection of the hydroxy group and transacetalization, gave optically active 1, 2-diol derivatives and the starting ene acetals in good yields. Haloetherification reaction of diastereomeric mixture of the ene acetals, derived from racemic norbornene aldehydes and chiral non-racemic (R, R)-hydrobenzoin, proceeded in a kinetically controlled manner to give the optically pure 8-membered acetal along with the intact ene acetal. Both acetals were converted to the optically pure norbrnene aldehydes in both enantiomeric forms.

本项目主要研究了基于烯缩醛分子内卤代醚化反应的不对称合成及其应用，主要包括两个方面：1）σ-对称二烯的不对称去对称化-多手性中心的合成; 2）对称二醇的不对称去对称化。1）σ-对称二烯的不对称去对称化-多手性中心的合成：以2，5-环己二烯-1-甲醛和手性氢化苯偶姻为原料，在甲醇存在下，与NBS发生分子内卤代醚化反应，立体选择性地得到了区别于两种烯烃的8元缩醛。剩余烯烃的硼氢化反应，然后氧化，得到环己烯酮衍生物。通过Grignard试剂的立体选择性1，4-加成，烯醇化阴离子的硅烷化，过量MeLi处理，然后与过量烯丙基碘进行二烯丙基化反应，得到了与百部生物碱的主要成分（-）-stenine具有相同碳骨架的化合物。2）对称二醇的不对称去对称化：以不饱和内消旋-1，2-二醇为原料，通过烯缩醛的不对称去对称化反应合成了不饱和环状和非环状内消旋-1，2-二醇，2-二醇。烯缩醛的分子内卤代醚化反应是合成八元缩醛的关键步骤，它是通过单烯与单烯的反应立体选择性地合成八元缩醛的。随后还原消除，然后保护羟基和缩醛化，得到光学活性的1，2-二醇衍生物和起始烯缩醛，产率良好。由外消旋α-烯醛和手性非外消旋（R，R）-氢化苯偶姻衍生的烯缩醛的非对映体混合物，在动力学控制下进行卤醚化反应，得到光学纯的八元缩醛沿着完整的烯缩醛。两种缩醛都转化为两种对映体形式的光学纯降冰片烯醛。