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

碳碳键的形成反应对于包括药物在内的构造或复杂和功能性化合物最为重要。 Wittig和相关反应已被广泛用于此目的，但是，在此反应中没有中央手性。这种类型的反应对不对称合成的应用涉及对对照（iastereo）主题羰基或其π面的歧视，另一种是对外星羰基化合物的动力学分辨率。特别是，如果成功开发动态版本，则以后的方法对光学活性化合物的合成具有重要的适用性。基于羰基基团的分化，具有轴向性手性binol的光学活性HWE（本垒打）试剂已被证明是在不对称烯烃中诱导的有效手性的。在这项研究中，检查了这些手性HWE试剂的阴离子的动力学分辨率，以开发出新的方法论……更多创建光学活跃的兴趣化合物或手性合成子。搜索最佳的反应条件，首先进行了不对称烯烃和相关反应，并发现二乙基锌作为碱是有效的。尽管环己酮衍生物的动力学分辨率令人失望，但是当将二醛的金属复合物用作外星底物时，获得了令人满意的化学和光学产量以及回收的起始材料的产生。此外，该方法已成功地应用于不自然异常氨基酸的创建。这就是研究源自外来氨基酸的氨基醛作为动力学分辨率的可能底物，并以光学活性形式提供有趣的氨基酸衍生物。此外，研究了试剂结构与对映选择性之间的关系。并进行了一些机械考虑，以预测产品的立体化学。最后，该方法应用于代表性医学萘普生的不对称合成。的确，仍然有一些需要进一步研究的房间，例如动态动力学分辨率，但是本研究可能会为创建包括药物在内的有趣的光学活性化合物提供新颖的方法。较少的

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)。

田中圭 他: "Enantioselective synthesis of allenecarboxylates from phenyl acetates through C-C bond forming reactions."Tetrahedron : Asymmetry,. 12(in press). (2001)

Kei Tanaka 等人：“通过 C-C 键形成反应从乙酸苯酯进行对映选择性合成：不对称性，”（2001 年）。