Study on Development and Application of Kinetic Resolution in Asymmetric Olefination

不对称烯化动力学拆分技术的发展及应用研究

• 批准号: 11470471
• 负责人: TANAKA Kiyoshi
• 金额: $ 8.32万
• 依托单位: UNIVERSITY OF SHIZUOKA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470471/
• 关键词: Asymmetric Olefination; Kinetic resolution; HWE Reagent; Aminoaldehyde; Abnormal Amino Acid; Fe-carbonyl Complex; Naproxen; BINOL; 光学分割; フォスホネート試薬; 鉄錯体

The carbon-carbon bond forming reactions are of most important for construction or complex and functional compounds including medicines. The Wittig and related reactions have been widely used for this purpose, however, no central chirality forms in this reaction. Application of this type of reaction to asymmetric synthesis involves discrimination of enantio (diastereo) topic carbonyl groups or their π-faces and the other is kinetic resolution of racemic carbonyl compounds. Especially, the latter approach has significant applicability to synthesis of optically active compounds, if dynamic version is successfully developed. The optically active HWE (Homer-Wadsworth-Emmons) reagents bearing axially chiral BINOL at the phosphonate moiety have been proven as effective chiral inducer in asymmetric olefination based on differentiation of carbonyl groups or their faces. In this study, the kinetic resolution by the anion of these chiral HWE reagents was examined to develop the novel methodology … More of creation of optically active interesting compounds or chiral synthons. Search of the optimum reaction conditions for asymmetric olefination and related reactions was first carried out and it was found diethyl zinc is effective as a base. Though the kinetic resolution of cyclohexanone derivative was disappointing results, satisfactory chemical and optical yields as well as those of the recovered starting materials were obtained when some metallic complexes of dialdehyde were used as racemic substrates. Furthermore, this methodology was successfully applied to the creation of unnatural abnormal amino acids. Thus, amino aldehydes derived from racemic amino acid was examined as possible substrates for kinetic resolution and to give interesting amino acid derivatives in optical active forms. Furthermore, the relationship between the structure of the reagents and enantioselectivity was investigated and some mechanistic consideration was carried out to predict the stereochemistry of products. Finally, the method was applied to asymmetric synthesis of a representative medicine naproxen. It is true that there are still some rooms for further investigation, such as dynamic kinetic resolution, but the present study might provide a novel method for creation of interesting optically active compounds including medicines. Less

碳-碳键形成反应对包括药物在内的复杂功能化合物的构建至关重要。Wittig反应及其相关反应已被广泛用于此目的，然而，在该反应中不形成中心手性。这类反应在不对称合成中的应用，包括对映（非映）位羰基或其π面的识别，以及外消旋羰基化合物的动力学分辨。特别是后一种方法，如果成功地开发出动态版本，则对光学活性化合物的合成具有重要的适用性。具有旋光性的HWE （homer - wadworth - emmons）试剂已被证明是一种有效的基于羰基或其表面分化的不对称烯烃手性诱导剂。在本研究中，研究了这些手性HWE试剂的阴离子动力学分解，以开发新的方法。首先对不对称烯烃及相关反应的最佳反应条件进行了探索，发现二乙基锌作为碱是有效的。虽然环己酮衍生物的动力学拆分结果令人失望，但以某些双醛金属配合物作为外消旋底物时，获得了令人满意的化学收率和光学收率以及回收的起始原料的收率。此外，该方法已成功应用于非自然的异常氨基酸的产生。因此，从外消旋氨基酸衍生的氨基醛被研究为动力学分辨率的可能底物，并以光学活性形式给出有趣的氨基酸衍生物。此外，还研究了试剂的结构与对映体选择性的关系，并从机理上对产物的立体化学进行了预测。最后，将该方法应用于代表性药物萘普生的不对称合成。虽然在动态动力学分辨率等方面仍有进一步研究的空间，但本研究可能为制备包括药物在内的有趣的光学活性化合物提供一种新的方法。少

项目成果

田中圭 他: "A Convenient One-Pot Synthesis of 2-Deoxy-2,3-didehydro-neuraminic Acid Derivatives."Chem.Pharm.Bull.,. 48(1). 163-165 (2000)

Kei Tanaka 等人：“2-脱氧-2,3-二脱氢-神经氨酸衍生物的便捷一锅法合成”。Chem.Pharm.Bull., 163-165 (2000)。

田中圭 他: "Use of 1,1'-Binaphthalene-8,8'-diol as a Chiral Auxiliary for Asymmetric Michael Addition.Application to the Syntheses of Turmeronol A and B."Chem.Pharm.Bull.,. 47(7). 1053-1055 (1999)

Kei Tanaka 等人：“使用 1,1-联萘-8,8-二醇作为不对称迈克尔加成的手性助剂。在姜黄醇 A 和 B 合成中的应用。”Chem.Pharm.Bull.,。 47（7）1053-1055（1999）。

田中圭 他: "Asymmetric Olefination of Metallic Arene or Diene Complexes to form Planar Chiral Complexes."Tetrahedron Lett.,. 40(36). 6599-6602 (1999)

Kei Tanaka 等人：“金属芳烃或二烯配合物的不对称烯化形成平面手性配合物”，40(36) 6599-6602 (1999)。

田中圭 他: "Synthesis of configurationally defined sexi-and octinaphthal-ene derivatives."Org.Lett.,. 3(2). 169-171 (2001)

Kei Tanaka 等人：“构型定义的六亚萘和辛亚萘衍生物的合成”，Org.Lett.，169-171 (2001)。

K.Tanaka et al.: "Asymmetric Olefination of Metallic Arene or Diene Complexes to form Planar Chiral Complexes."Tetrahedron Lett.. 40 (36). 6599-6602 (1999)

K.Tanaka 等人：“金属芳烃或二烯配合物的不对称烯化形成平面手性配合物。”Tetrahedron Lett.. 40 (36)。