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.

在本项目中，我们研究了基于烯缩醛分子内卤醚化的不对称合成及其在两个方面的应用：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：分子内由2,5-环己二烯-1-甲醛和手性氢苯偶姻制备的烯缩醛在MeOH存在下用NBS处理，进行卤醚化反应，立体选择性地进行，得到8元缩醛二烯烃，随后对剩余的烯烃进行硼氢化。通过氧化得到环己烯酮衍生物的立体选择性1, 4-加成。格氏试剂，烯醇阴离子的甲硅烷基化，过量的MeLi处理，然后用过量的烯丙基碘进行二烷基化，得到具有与百部生物碱的主要成分(-)-stenine相同的碳骨架的化合物。2) 对称二醇的不对称去对称化：不对称不饱和环状和无环内消旋 1, 2-二醇的去对称化是由烯缩醛开发而成，由以下物质制备降冰片烯甲醛和不饱和内消旋1, 2-二醇的分子内卤醚化作为关键步骤，仅通过降冰片烯烯烃的反应以立体选择性方式提供8元缩醛，然后进行保护。羟基和转缩醛化，得到光学活性的 1, 2-二醇衍生物和起始烯缩醛衍生自外消旋降冰片烯醛和手性非外消旋(R,R)-氢安息香的烯缩醛的非对映体混合物的卤醚化反应以动力学控制的方式进行，得到光学纯的8元缩醛以及完整的缩醛。两种缩醛均转化为两种对映体形式的光学纯降冰烯醛。