Design of a Chiral Dinucleating System Utilizing Tartaric Acid Ester as a Chiral Auxiliary and Its Application to the Synthesis of Optically Active Compounds

以酒石酸酯为手性助剂的手性双核体系设计及其在光学活性化合物合成中的应用

基本信息

批准号：
10640515
负责人：
UKAJI Yutaka
金额：
$ 2.5万
依托单位：
Kanazawa 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

It is strongly required to develop a practical and efficient method for the construction of chiral molecules to explore new biologically active medicines and agricultural chemicals. In this research, a new and novel chiral system possessing two metal centers utilizing tartaric acid esters was designed ; that is, if two reactants are bound to two different metal centers of the dialkoxide derived from tartaric acid ester, which might actually form the rigid 5/5-fused bicyclic dinucleating structure, they might be ideally oriented and/or activated by the metals and the following reaction might proceed in an enantioselective manner to afford the corresponding optically active products.The asymmetric 1,3-dipolar cycloaddition of nitrile oxides to ethyl (E)-4-hydroxy-2-butenoate was achieved by the use of diisopropyl (R,R)-tartrate as a chiral auxiliary to afford the corresponding 4,5-trans-2-isoxazolines, which were transformed to the corresponding 4,5-cis-2-isoxazolines by the treatment with a base through isomerization and lactonization.The asymmetric addition of the Reformatsky-type reagent, prepared in situ from diethylzinc and iodoacetic acid ester, to a carbon-nitrogen double bond in 3,4-dihydroisoquinoline N-oxides was achieved with enantioselectivity up to 86% ee. Furthermore, the asymmetric addition of the Reformatsky-type reagent to imines prepared from aldehydes and 2-aminophenol was also achieved to give β-amino acid derivatives. In order to realize reproducible higher stereoselection, the addition of a small amount of water was crucial.

强烈需要开发一种实用有效的方法来构建手性分子来探索新的具有生物活性的药物和农业化学品。在这项研究中，设计了一种使用tart酸酯的新型手性系统，该系统具有两个金属中心。也就是说，如果两个反应物与源自tart酸酯的两个不同金属中心结合，实际上可能形成了刚性5/5粘合的双型二元结构的刚性的刚性，则可能是由金属取向和/或激活的，并且以下反应以相应的启发性旋转为单位。通过使用二异丙基（r，r） - 二苯二甲酸乙二醇（E）-4-羟基-2-二苯甲酸酯二苯甲酸酯，从而实现二异丙基（R，R） - 二苯甲酸酯作为手性辅助，以提供相应的4,5-TRANS-2-TRANS-2-异沙唑，这些辅助因素通过与相应的4,5-CIS-2-异氧化物的层次进行了调查。从二乙基和碘乙酸酯原位制备的重构型试剂，到3,4-二羟基苯胺N-氧化物中的碳氮双键，可实现高达86％EE的对映选择性。此外，还可以将重大型试剂不对称地添加到由醛和2-氨基苯酚制备的亚胺中，以产生β-氨基酸衍生物。为了实现可再现的更高立体选择，少量水的添加至关重要。