Creation of C2-Symmetric Molecules using An Asymmetric Dihydroxylation and Its Application

不对称二羟基化制备C2对称分子及其应用

基本信息

批准号：
07672260
负责人：
TAKAHATA Hiroki
金额：
$ 1.54万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672260/
关键词：
Asymmetric Dihydroxylation C_2-Symmetric Molecules Chiral Auxirality Enantiomeric Enhancement Piperidine

项目摘要

Since chiral C_2-symmetric molecules play an important role in an asymmetric synthesis, much attention has increasingly been focused on their asymmetric synthesis. We describe a promising route to C_2-symmetric tetraols involving the Sharpless asymmetric dihydroxylation (AD) of symmetric terminal dienes and its application to the synthesis of C_2-symmetric chiral amines the representative of chiral auxiliaries of wide use.The precedent established by the Sharpless group suggested that enantiomeric excess in the case of terminal olefins might be modest (more or less 80% ee). In a symmetrical diene such as the twin olefins conjoined, we anticipate that the stereoselectivity might be improved based on the following consideration : The first AD reaction produces the major and minor enantiomers (diols). Since each enantiomer undergoes the second AD reaction with essentially the same enantiofacial selectivity as in the first AD reaction, three tetraol products result ; a C_2-symmetry compound 1, a meso compound, and ent-1. The overall consequence is that most of the AD reaction resulting from the undesired enantiofacial attack leads to the meso compound. Very little of the mirror image compound ent-1 is formed, and therefore the enantiomeric purity of the major C_2-symmetry product 1 will be high. Based on these consideration, the C_2-symmetric teraols are prepared indeed in high enantiomeric purities from dienes (1,5-hexadiene, 1,6-heptadiene, and ally1 ether). Subsequently, the tetraols are transformed into C_2-symmetric OMICRON-protected alpha, alpha'-bishydroxymethylpyrrolidines, piperidines, and morphorine. Interestingly, we found that medium-pressure chromatography on silica gel of pyrrolidines and piperidines with modest enantioselectivity resulted in efficient enantiomeric fractionation.

由于手性C_2对称分子在不对称合成中起重要作用，因此越来越关注其不对称合成。我们描述了C_2对称四醇的有前途的途径，涉及对称末端二enes的不对称二羟基化（AD）及其在C_2合成C_2对称性手胺的合成中的应用。建议在末端烯烃的情况下，对映体过量可能是适度的（或多或少的80％EE）。在诸如双烯烃等对称的二烯中，我们预计立体选择性可以根据以下考虑来提高：第一个AD反应会产生主要和次要的对映异构体（DIOLS）。由于每个对映异构体都具有与第一个AD反应相同的对映异构选择性的第二个AD反应，因此产生了三种四酚产物。 C_2对称化合物1，MESO化合物和ENT-1。总体后果是，由不希望的对映射攻击产生的大多数AD反应导致了中质化合物。很少形成镜像化合物ENT-1，因此主要C_2对称产物1的对映体纯度将很高。基于这些考虑，C_2对称的Teraols确实是在二enes（1,5-己二烯，1,6-己二烯和Ally1醚）的高对映体纯度中制备的。随后，将四酚转化为C_2对称Omicron保护的α，α'-甲基二甲基甲基吡咯烷酮，哌啶和形成碱。有趣的是，我们发现具有适度的对映选择性的吡咯烷和哌啶的硅胶凝胶上的中压色作用导致有效的对映体分馏。