Development of Asymmetric Catalysis of Synthetic Reactions

合成反应不对称催化的进展

• 批准号: 02403020
• 负责人: NAKAI Takeshi
• 金额: $ 20.8万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02403020/
• 关键词: Asymmetric Synthesis; Asymmetric Catalysis; Aldol Reaction; Ene Reaction; Diels-Alder Reaction; Titianium Complex; Claisen Rearrangement; Europium Complex; アルド-ル反応; DielsーAlder反応; Claisen転位; ランタニド錯体; ランタノイド触媒; 立体制御; 分子認識

The purpose of this work is to develop efficient asymmetric catalysis of some C-C bond forming reactions. A summary of the research results is as follow: (1) Catalytic Stereocontrol in Asymmetric Aldol reactions : Using Eu(III)-complexes as a catalyst, high levels of distereocontrol have been achieved in the aldol reactions of chiral alpha-amino aldehydes with ketene silyl acetals Furthermore, the catalytic aldol technology has successfully been applied to asymmetric synthesis of the key intermiediates of carbapenem antibiotics and renin inhibitors. (2) Asymmetric catalysis of Carbonyl-Ene Reactions : The chiral titanium complex derived from optically active binaphthol was found to serve as an efficient asymmetric catalyst for glyoxylate-ene reaction to provide a practical access to alpha-hydroxy esters in high enantiomeric excess. Interestingly, the phenomenon of "asymmetric amplification" was observed and its mechanistic origin was elucidated. (3) Asymmetric Catalysis of Diels-Alder Type Reactions : The above-mentioned chiral titanium comples was found to serve as an asymmetric catalyst for hetero D.-A. reaction with the glyoxylate and D.-A.reactions with methacrolein and quinones. (4) Asymmetric Catalysis of Allylmetal/Aldehyde Addition Reactions : The abovementioned chiral Ti-complex was also found to be an efficient asymmetric catalyst for the addition reactions of allylic silanes and stannanes to the glyoxylate. (5) Asymmetric Catalysis of Claisen Rearrangement : A palladium (II) complex was found to show an efficient and diastereoselective catalysis of the Claisen rearrangement via an ether exchange process. However, the development of an asymmetric catalyst has been still unsuccessful. Further work is in progress.

本工作的目的是发展一些C-C键形成反应的高效不对称催化。主要研究结果如下：（1）不对称Aldol反应中的催化立体控制：在Eu（III）配合物催化下，手性α-氨基醛与烯酮甲硅缩醛的Aldol反应实现了高度的立体控制，并成功地应用于碳青霉烯类抗生素和肾素抑制剂关键中间体的不对称合成。(2)羰基-烯反应的不对称催化：发现衍生自光学活性联萘的手性钛络合物作为乙醛酸酯-烯反应的有效不对称催化剂，以提供高对映体过量的α-羟基酯的实际途径。有趣的是，“不对称扩增”的现象被观察到，其机制的起源被阐明。(3)Diels-Alder型反应的不对称催化作用：发现上述手性钛配合物可作为杂D.- A.与乙醛酸酯和D.-与甲基丙烯醛和醌的反应。(4)烯丙基金属/醛加成反应的不对称催化：还发现上述手性Ti络合物是烯丙基硅烷和锡烷与乙醛酸酯的加成反应的有效不对称催化剂。(5)Claisen重排的不对称催化：发现钯（II）络合物通过醚交换过程显示出对Claisen重排的有效和非对映选择性催化。然而，不对称催化剂的开发仍然不成功。进一步的工作正在进行中。

项目成果

Koichi MIKAMI,Masahiro TERADA,Eiji SAWA,Takeshi NAKAI: "Asymmetric Catalysis by Chiral Titanium Perchlorate for Carbonyl-Ene Cycization" Tetrahedron Letter. 32. 6571-6574 (1991)

Koichi MIKAMI、Masahiro TERADA、Eiji SAWA、Takeshi NAKAI：“手性高氯酸钛对羰基烯环化的不对称催化”四面体字母。

Jin-Hua GU,Mikako OKAMOTO,Masahiro TERADA,Koichi MIKAMI,Takeshi NAKAI: "Unique Stereocontrol in Europium(III)-Catalyzed Cyanosilylation of Chiral α-Alkoxy and α-Amino Aldehydrs" Chemistry Letters. 1169-1172 (1992)

Jin-Hua GU、Mikako OKAMOTO、Masahiro TERADA、Koichi MIKAMI、Takeshi NAKAI：“铕 (III) 催化手性 α-烷氧基和 α-氨基醛的氰基硅烷化的独特立体控制”化学快报 1169-1172。

Takeshi Nakai: Organic Synthesis in Japan: Past, Present, and Future. Pericyclic Approach to Stereochemical Control: Acyclic Stereocontrol via [2,3]Wittig Rearrangement and Asymmetric Catalysis of Glyoxylate-Ene Reaction, 267-274 (1992)

Takeshi Nakai：日本的有机合成：过去、现在和未来。

三上 幸一: "“Chemzyme"の創製,不斉触媒的カルボニルーエン反応の開発をケ-ス・スタディ-として" 油化学. 39. 129-137 (1990)

Koichi Mikami：“‘Chemzyme’的创建，不对称催化羰基甲苯反应的开发作为案例研究”《石油化学》39. 129-137 (1990)。

Fumiyuki Shirai: "Diastereofacial Selection in Titanium TetrachlorideーPromoted Aldol Reactions with the Silyl Ketene Acetal of Methyl (R)ー3ーHydroxybutanoate" Chemistry Letters. 1931-1934 (1990)

Fumiyuki Shirai：“四氯化钛促进的羟醛反应与 (R)-3-羟基丁酸甲酯的甲硅烷基乙烯酮缩醛的非对映选择”化学快报 1931-1934 (1990)。