Development of Highly Efficient and Practical Chiral Rare Earth Catalysts and Its Use

高效实用手性稀土催化剂的研制及其应用

基本信息

批准号：
12555254
负责人：
INANAGA Junji
金额：
$ 8.83万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12555254/
关键词：
Chiral Lanthanum Catalyst Catalytic Asymmetric Epoxidation Optically Active Epoxy Ketone Chiral Scandium Catalyst Asymmetric Michael Reaction Optically Active Keto Aziridine Catalytic Asymmetric Aziridination 光学活性希土類錯体キラル希土類ルイス酸触媒不斉へテロ

项目摘要

Fine-tuning of the preparation conditions of our recently developed catalyst system [La(O-i-Pr)_3/(R)-BINOL/Ph_3PO/cumene hydroperoxide] for the asymmetric epoxidation of conjugated enones as well as the epoxidation conditions was carried out. To be more precise, influence of various factors, such as (1) ratio of the components of the catalyst, (2) amount and concentration of the catalyst to each substrate, (3) addition time of the substrates, and (4) reaction temperatures, was carefully examined. As a result, we succeeded in the preparation of the desired epoxy ketones in over 90 % chemical yields with over 97 % ee in large-scale experiments using 20 kg - 80 kg of substrates. Furthermore, the resulting epoxy ketones with high optical purities were successfully converted into the corresponding anti-α-amino-β-hydroxy acid derivatives, which are medicinally or pharmaceutically important substances, accompanying no epimerization.On the other hand, the chiral scandium complex Sc[(R)-BNP]_3 … More , previously developed by us as a novel Lewis acid catalyst, was found to promote the enantioselective Michael addition of O-alkylhydroxylamines to conjugated enones. Thus, a variety of β-alkoxyamino ketones were synthesized in high yields and enantioselectivities (up to 99 % ee). The Michael adducts were cleanly converted into the corresponding aziridines by the treatment with a base catalyst like NaO-t-Bu. As these two catalytic reactions proceed at room temperature and almost quantitatively afford the products with high optical purities, the present two-step process provides a highly practical way to optically pure α-keto aziridines, another pharmaceutically important family of synthetic intermediates. We also found that the α-keto aziridines can be converted to the syn-α-amino-β-hydroxy ketones under the N-acetylation conditions.Therefore, the possible four diastereomers of α-amino-β-hydroxy acid derivatives may be prepared in optically pure forms from a common substrate by utilizing the chiral lanthanum-catalyzed epoxidation and the chiral scandium-catalyzed Michael reaction of conjugated enones developed in this study. Less

对我们最近开发的共轭烯酮不对称环氧化催化剂体系[La(O-i-Pr)_3/(R)-BINOL/Ph_3PO/氢过氧化异丙苯]的制备条件以及环氧化条件进行了微调。更准确地说，是各种因素的影响，例如（1）催化剂组分的比例，（2）催化剂对每种底物的量和浓度，（3）添加时间仔细检查了底物的温度和 (4) 反应温度，结果，我们在使用 20 kg - 80 的大规模实验中成功制备了所需的环氧酮，化学产率超过 90%，ee 超过 97%。此外，所得到的具有高光学纯度的环氧酮被成功转化为相应的抗α-氨基-β-羟基酸衍生物，这些衍生物是医药学上重要的物质，并伴随着。另一方面，我们之前开发的新型路易斯酸催化剂手性钪络合物Sc[(R)-BNP]_3 … More被发现可以促进O-烷基羟胺与共轭烯酮的对映选择性迈克尔加成因此，以高产率和对映选择性（高达 99% ee）合成了多种 β-烷氧基氨基酮。通过用NaO-t-Bu等碱催化剂处理，可以干净地转化为相应的氮丙啶。由于这两个催化反应在室温下进行，并且几乎定量地提供了具有高光学纯度的产物，因此本两步法提供了高度光学纯度的产物。光学纯α-酮氮丙啶的实用方法，另一个药学上重要的合成中间体家族我们还发现α-酮氮丙啶可以在以下条件下转化为顺式-α-氨基-β-羟基酮。 N-乙酰化条件。因此，通过利用手性镧催化的环氧化反应和手性钪催化的共轭迈克尔反应，可以从共同的底物中制备光学纯形式的α-氨基-β-羟基酸衍生物的四种非对映异构体。本研究中开发的烯酮较少。