Development of Chiral Nucleophilic Catalysts

手性亲核催化剂的开发

• 批准号: 09672142
• 负责人: KAWABATA Takeo
• 金额: $ 1.92万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672142/
• 关键词: nucleo philec catalyst; kiretic resolution; acylation; induced fit; alcohel; 求核触媒; アミノアルコール; 速論的光学分割; 速度論的光学分割; π-π interaction; attractive interaction; 遠隔不斉誘起; ジメチルアミノピリジン

A new chiral nucleophilic catalyst was developed, which consists of 4-pyrrolidinopyridine moiety as a an active site and 2-naphthylmethyl group as a stereo-controlling site. The catalyst promotes the kinetic resolution of racemic secondary alcohols through enantioselective acylation at ambient temperature. Treatment of several racemic alcohols with 5 mol % of the catalyst and 0.7 mol equivalent of isobutyric anhydride gave enantiomerically pure (>99% ee) recovered alcohols at -70 % conversion (selectivity factor (s) - 9 21).The mechanism of the catalytic asymmetric acylation was investigated by means of NOB studies of the catalyst as well as the reactive acylpyridinium intermediate. The catalyst adopts a conformation in which the pyridine ring does not interact with the naphthalene ring in its ground state. Thus, a facile reaction takes place with acid anhydride. On the other hand, close proximity of the pyridine ring with the naphthalene ring was observed in the acylpyridinium intermediate, which would be caused by the attractive pi-pi interaction between electron-deficient acylpyridinium pi-system and the electron-donating naphthalene ring. Informative NOE's suggest that the enantio-face of the carbonyl group of the acylpyridinium ion is totally controlled. The reorganization of the catalyst triggered by binding of the specific substrate (acid anhydride) is referred to as an "induced-fit" process. The process would be the key for the catalyst to show high enantio-differentiating ability without retarding its high catalytic activity.

开发了一种新的手性亲核催化剂，该催化剂以4-吡咯并吡啶为活性中心，以2-萘甲基为立体控制中心。该催化剂在室温下通过对映选择性酰化反应促进外消旋仲醇的动力学拆分。用5mol%的催化剂和0.7mol当量的异丁酸酐处理几种外消旋醇，在~ 70%的转化率（选择性因子~ 921）下得到了对映体纯（> 99%ee）的回收醇。通过对催化剂和反应性酰基吡啶中间体的NOB研究，探讨了催化不对称酰化反应的机理。该催化剂采用吡啶环不与处于基态的萘环相互作用的构象。因此，与酸酐发生容易的反应。另一方面，在酰基吡啶中间体中观察到吡啶环与萘环的紧密接近，这可能是由缺电子酰基吡啶π-系统与供电子萘环之间的吸引π-π相互作用引起的。信息NOE的建议，酰基吡啶离子的羰基的对映体面是完全受控的。由特定底物（酸酐）的结合引发的催化剂的重组被称为“诱导配合”过程。该工艺是使催化剂在不影响其高催化活性的前提下表现出高对映体区分能力的关键。

项目成果

Takeo Kawabata: "Nonenzy matic Kinetic Resolution of Racemic Alcohols through an "Induced Fit"Process" J.Am.Chem.Soc.119・13. 3169-3170 (1997)

Takeo Kawabata：“通过“诱导拟合”过程非酶动力学拆分外消旋醇”J.Am.Chem.Soc.119・13 (1997)。

TAKEO KAWABATA: "Nonenzymatic Kinetic Resolution of Racemic Alcohoos through an "Induced Fit"Process." J.Am.Chem.Soc. 119(13). 3169-3170 (1997)

TAKEO KAWABATA：“通过“诱导拟合”过程非酶动力学拆分外消旋醇。”

Takeo Kawabata: "Nonenzymatic Kinetic Resolution fo Racemic Alcohols through on “Induced Fit"Process" J.Am.Chem.Soc.119 (13). 3169-3170 (1997)

Takeo Kawabata：“通过“诱导拟合”过程进行外消旋醇的非酶动力学拆分”J.Am.Chem.Soc.119 (13) 3169-3170 (1997)。

Takeo, Kawabata: "Nonenzymatic kinetic Resolution of Racemic Alcohols through on “Induced Fit" Process" J.Am.Chem.Soc.119(13). 3169-3170 (1997)

Takeo, Kawabata：“通过“诱导拟合”过程非酶动力学拆分外消旋醇”J.Am.Chem.Soc.119(13) (1997)。