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.

由于环境良性和轻度反应条件，有机刻分析一直是当前合成注意的重点。我们已经开发了一种手性4-吡啶吡啶（PPY）类似物，该类似物在催化活性吡啶氮附近没有手性元素。然而，该催化剂在用P-二甲基氨基苯甲酰氮酰基保护组的外消毒氨基醇的动力学分辨率中显示出高的对映选择性（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。发现使用催化剂的氨基醇衍生物的酰化速率是使用PPY的速度12倍。还开发了C_2对称性手性PPY类似物。关键的中间体，2,5-二羧基-N-吡啶基吡咯烷酮，是通过从L-谷氨酸开始的五步序列获得的。很容易实现在C（2）和C（5）处的功能侧链的组合引入，因此，完成了手性C_2对称PPY的小库。所有这些新的PPY类似物均显示出高催化活性用于酰化，因为在催化活性吡啶氮附近没有空间充血。它们在室温下显示出极好的选择性，在酰基化的不对称循环中二醇中表现出极好的选择性。

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

Preparation and properties of chiral 4-pyrrolidinopyridine (PPY) analogues with dual functional side chains

• DOI: 10.1016/s0040-4039(03)00021-2
• 发表时间: 2003-02-17
• 期刊: TETRAHEDRON LETTERS
• 影响因子: 1.8
• 作者: Kawabata, T;Stragies, R;Fuji, K
• 通讯作者: Fuji, K