Development of a New Generation of Nucleophilic Catalysts and their Use in Selective Reactions

新一代亲核催化剂的开发及其在选择性反应中的应用

• 批准号: 14370721
• 负责人: KAWABATA Takeo
• 金额: $ 8.83万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370721/
• 关键词: nucleophilic catalysts; acylation; kinetic resolution; regioselectivity; desymmetrization; remote asymmetric induction; acceleration; 不斉求核触媒; エナンチオ選択性; 基質特異性; 不斉非対称化; π-π相互作用; ピロリジノピリジン; 気質特異性; C_2-対称

Organocatalysis has been the focus of curent synthetic attention due to environmental benignity and the mild reaction conditions. We have developed a chiral 4-pyrrolidinopyridine (PPY) analogue which has no chiral elements near the catalytically active pyridine nitrogen. Nevertheless, this catalyst shows high enantioselectivity (s=10〜54) in the kinetic resolution of racemic amino alcohols with a p-dimethylaminobenzoyl protective group. In this research project, the mechanism for the enantioselective acylation and enantioselective acceleration was clarified. The rate of acylation of an amino alcohol derivative with the catalyst was found 12 times as fast as that with PPY. C_2-symmetric chiral PPY analogues were also developed. A key intermediate, 2,5-dicarboxyl-N-pyridyl-pyrrolidine, was obtained via a five-step sequence starting from L-glutamic acid. Combinatorial introduction of the functional side chains at C(2) and C(5) is readily achieved, thus, construction of a small library of chiral C_2-symmetric PPYs was accomplished. All of these new PPY analogues showed high catalytic activity for acylation of alcohols, because of no steric congestion near the catalytically active pyridine nitrogen. They showed excellent selectivity in acylative asymmetric desymmetrization of cyclic meso-diols at room temperature.

有机催化由于环境友好、反应条件温和而成为当前合成关注的焦点。我们开发了一种手性 4-吡咯烷吡啶 (PPY) 类似物，它在催化活性吡啶氮附近没有手性元素。尽管如此，该催化剂在具有对二甲氨基苯甲酰保护基团的外消旋氨基醇的动力学拆分中表现出较高的对映选择性（s=10〜54）。在该研究项目中，阐明了对映选择性酰化和对映选择性加速的机制。发现用该催化剂酰化氨基醇衍生物的速率是用 PPY 酰化的速率的 12 倍。还开发了 C_2-对称手性 PPY 类似物。从 L-谷氨酸开始，通过五步序列获得了关键中间体 2,5-二羧基-N-吡啶基-吡咯烷。 C(2)和C(5)处功能侧链的组合引入很容易实现，因此，完成了手性C_2对称PPY的小型文库的构建。所有这些新的 PPY 类似物都对醇的酰化表现出高催化活性，因为催化活性吡啶氮附近没有空间拥挤。它们在室温下对环状内消旋二醇的酰化不对称去对称化表现出优异的选择性。

项目成果

Takeo Kawabata: "Preparation and Properties of Chiral 4-Pyrrolidinopyridine (PPY Analogues with Dual Functional Side Chains"Tetrahedron Letters. 44・8. 1545-1548 (2003)

Takeo Kawabata：“手性 4-吡咯烷吡啶（具有双功能侧链的 PPY 类似物）的制备和性质”Tetrahedron Letters. 44・8. 1545-1548 (2003)

A Facile Synthesis of Tetrahydroisoquinoline and Tryptoline Derivatives with a Quaternary carbon Center at C(3)

季碳中心位于 C(3) 的四氢异喹啉和色氨酸衍生物的简便合成

• 发表时间: 2003
• 期刊: Synthesis
• 作者: T.Kawabata

川端猛夫: "四置換炭素の不斉構築"ファルマシア. 39・7. 672-673 (2003)

Takeo Kawabata：“四取代碳的不对称结构”Pharmacia 39・73（2003）。

Chirality Transfer during Alkylation of Chiral Amides

手性酰胺烷基化过程中的手性转移

• 发表时间: 2003
• 期刊: Chem Comm.
• 作者: Tada A;Watanabe T;Yokoe H;Hanada N;Tanzawa H.;T.Kawabata
• 通讯作者: T.Kawabata

Control of the Enantioselectivity of Alkylation of Phenylalanine Derivatives by Regulation of the Aggregate Structure of Chiral Enolate Intermediates

通过调节手性烯醇化物中间体的聚集结构来控制苯丙氨酸衍生物烷基化的对映选择性

• 发表时间: 2003
• 期刊: Tetrahedron 59
• 作者: Takayama;H.;Y.Misono;M.Anada et al.;T.Kawabata
• 通讯作者: T.Kawabata