Asymmetric Synthesis Using Chiral Lewis Base

使用手性路易斯碱的不对称合成

• 批准号: 04557097
• 负责人: TOMIOKA Kiyoshi
• 金额: $ 3.14万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557097/
• 关键词: Asymmetric synthesis; Chiral catalyst; Organolithium; Amino ether; Chiral ether; beta-Lactam; Amines; Catalytic reaction; キラル分子; 炭素一炭素結合; 軸不斉; C2対称

Chiral Lewis base coordinates to metallic center of metallic reagents and activates the reagent. Consequently, it is highly probable that stereochemical control of the reaction would be achieved by coordination of the chiral Lewis base to metal. However, the use of chiral Lewis base in the reaction is quite rare in the modern synthetic chemistry. This is clearly contrasted to the familiar use of chiral Lewis acid as activator as well as stereoconytoller.In the present research we focused on design, synthesis, and application of chiral Lewis base into asymmetric synthesis. Moreover, we applied the chiral Lewis base as a chiral catalyst in the reaction which can produce optically active compounds more than the equivalence of the chiral catalyst.As a result of the studies we developed quite promising reactions as shown below.1. Asymmetric synthesis of beta-lactam of more than 90% ee by the reaction of lithium ester enolate with imine in the presence of chiral amino ether catalyst.2. Catalytic asymmetric synthesis of highly optically active beta-lactam using catalytic amount of chiral amino ether.3. Catalytic asymmetric synthesis of amines of more than 90% ee by the reaction of organolithium with imines.These promising results may open a new world of synthetic organic chemistry and its application to the industrial production.

手性路易斯碱指向金属试剂的金属中心并激活试剂。因此，极有可能通过手性路易斯碱与金属的配位来实现反应的立体化学控制。然而，在现代合成化学中，手性路易斯碱在反应中的使用是相当罕见的。这与我们熟悉的手性路易斯酸作为激活剂和立体控制器形成鲜明对比。本文主要研究了手性路易斯碱的设计、合成及其在不对称合成中的应用。此外，我们将手性路易斯碱作为手性催化剂应用于该反应中，可以产生比手性催化剂更具有光学活性的化合物。作为研究的结果，我们开发了如下所示的相当有希望的反应。手性氨基醚催化下烯酸锂与亚胺不对称合成ee大于90%的β -内酰胺用手性氨基醚催化量催化不对称合成高旋光性β -内酰胺。有机锂与亚胺反应催化不对称合成ee含量大于90%的胺。这些有希望的结果将为合成有机化学及其在工业生产中的应用开辟一个新的领域。

项目成果

富岡 清、他3名: "有機化学実験ガイド" 廣川書店, 155 (1993)

富冈清等3人：《有机化学实验指南》广川书店，155（1993）

M.Kanai et al: "Solvent Effect and NMR Behaviour in a Chiral Amidophosphine Mediated Reaction of Organocuprate with Chalcone" J.Chem.Soc.,Chem.Commun.16. 1248-1249 (1993)

M.Kanai 等人：“手性氨基膦介导的有机铜酸盐与查尔酮反应中的溶剂效应和 NMR 行为”J.Chem.Soc.，Chem.Commun.16。

K.Tomioka, M.Shindo K.Koga.: "Asymmetric Addition of Aryllithiums to Naphthalene BHA-Esters Catalyzed by a Chiral Ligand." Tetrahedron Letters. 34. 681-682 (1993)

K.Tomioka、M.Shindo K.Koga.：“手性配体催化芳基锂不对称加成到萘 BHA 酯”。

Kiyosi Tomioka: "Asymmetric Addition of Aryllithiums to Naphthalene BHA-Esters Catalyzed by a Chiral Ligand" Tetrahedron Letters. 34. 681-682 (1993)

Kiyosi Tomioka：“手性配体催化芳基锂与萘 BHA 酯的不对称加成”四面体字母。

Kaori Ando: "Asymmetric Alkylation of α-alkyl β-Keto Esters to α,α-Alkyl β-Keto Esters Havin (R)-or(S)-Chiral Quatemary Center" Tetrahedron. 49. (1993)

Kaori Ando：“α-烷基 β-酮酯不对称烷基化为 α,α-烷基 β-酮酯 Havin (R)-或(S)-手性四元中心”四面体 49。