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.

在该项目中，我们研究了不对称合成的基于分子内孤立素化的分子内孤立素化的分子内分子内甲螺栓化的分子内分子甲状结晶的分子内分子卤素化反应的分子内置化甲壳质化，在2,5,-二甲酰胺二胺的eme中，在EME乙酰乙烯甲乙烯的存在下用NBS处理NBS的NBS处理， Hydrobenzoin进行了立体选择性，以给出8元的乙酰含量歧视的两个烯烃。剩余的烯烃随后的水合氧化提供了环己酮衍生物。 Stereoselective 1, 4-addition of Grignard reagent, silylation of enolated anion, exceed MeLi treatment, then diallylation with excess allyl iodide Afforded the compound with the same carbon skeleton of (-)-stenine, a major component of steroids.2) Asymmetric desymmetricalization of symmetric diols: An asymmetric desymmetricalization of unsaturated cyclic and环环中的2-二醇是由ene actals开发的，是由诺尔伯烯羧甲醛和不饱和中二二醇和2-二醇制备的。 eNe乙烯的分子内成积作为关键步骤，仅通过诺伯烯烯烃的反应以立体选择性的方式提供了8元的acetals。随后的消除减少，然后保护羟基和透射率化，给出了光学活跃的1、2-二醇衍生物和良好产量的起始Ene actals。源自埃氏乙烯的非对非那一组混合物的孤立性反应，这些混合物衍生自源自悬子醛烯醛和手性非流行病（R，R） - 氢苯，以运动控制的方式进行，使光学上纯的8-MERBERED乙酰乙烯与完整的Enacetal一起进行。两种乙酰座都以两种对映体形式转化为光学纯的北甲醛。