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

• 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; 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

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

我们最近开发的催化剂系统[LA（O-I-PR）_3/（R）-binol/pH_3PO/Cumene hydroxoxide]的制备条件进行微调，以进行共轭燃料的不对称环氧化以及环氧条件。更确切地说，各种因素的影响，例如（1）催化剂的成分的比率，（2）催化剂与每个底物的量和浓度，（3）底物的添加时间以及（4）反应温度，仔细检查。结果，我们成功地制备了超过90％的化学产率的所需环氧酮，使用20 kg -80 kg的底物，在大规模实验中，EE超过97％。 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, taking part in no episode.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对映选择性迈克尔添加了O-烷基羟胺胺将烯烃缀合。这是多种β-烷氧基氨基酮酮以高产量和对映选择性（最高99％的EE）合成。通过使用像Nao-T-Bu这样的基础催化剂处理，将迈克尔加合物清晰地转化为相应的Aziridines。随着这两种催化反应在室温下进行，几乎定量地提供具有高光纯度的产品，目前的两步过程为光学上纯净的α-酮酮Aziridines提供了一种高度实用的方法，这是另一个具有物理上重要的合成中间体系列。我们还发现，在N-乙酰化条件下，可以将α-酮二吡啶转化为Syn-α-氨基-β-羟基酮酮。因此，可以通过使用普通的chiral suptrate和chiral prestrate形成chiral suptrate的α-氨基-β-羟基酸衍生物的α-氨基 - β-羟基酸衍生物的四个可映异构体，可以使e e级升级化制备。在这项研究中，扫描酶催化的迈克尔反应。较少的