Construction of Asymmetric Space and Catalytic Stereoselection with C_2-Symmetrical Molecules

C_2对称分子的不对称空间构建与催化立体选择

• 批准号: 06640765
• 负责人: YODA Hidemi
• 金额: $ 1.34万
• 依托单位: Shizuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06640765/
• 关键词: Bisoxazoline; Chiral Ligand; Metal Complex; Amino Acid; Tartaric Acid; C_2-Imide; Nucleophilic Addition; Deoxygenation; オキサゾリン

1. According to my research scheme, asymmetric catalyst with the bisoxazoline ring system could be obtained from the coupling reaction of 2 equiv.of chiral amino alcohols with malononitrile-derived imidate and its activity as a chiral catalyst was investigated based on the alkylation of benzaldehyde with diethylzinc. Consequently, this reaction proceeded in about 40% ee.2. Consecutive treatment of C_2-symmetrical imides elaborated from L-tartaric acid with Grignard reagent and NaBH_4 afforded separable diastereomixture of chiral amide alcohols in high selectivity. Using these amide alcohols as catalysts, asymmetric alkylation with diethylzinc was investigated and the results are as follows ;(1) increasing a steric bulkiness of the N-substituent leads to an increase of the enantioselectivity.(2) maximally the catalyst recycles 18.8 times.(3) higher selectivity was obtained in the case of the catalyst with (4S)-configuration.(4) to enhance the selectivity ether is preferable over toluene as a solvent.Further, cyclic amides derived from D-arabinofuranose were also submitted to the same type of chiral catalytic reactions. It is interesting that no procedure for the asymmetric reactions with diethylzinc employing such as amide alcohols of cyclic amides as chiral catalysts has so far appeared.3. In addition to these reactions, asymmetric total syntheses of antibiotics, (-)-anisomycin and (+)-preussin were accomplished employing stereoselective nucleophilic addition and asymmetric deoxygenation of the hydroxy lactam intermediate elaborated from the same starting material, arabinofuranose.13EA09 : In summary, two new types of chiral ligands were prepared and investigated based on their catalytic activity and two antibiotic natural products were synthesized.

1. 根据我的研究方案，由2等份的手性氨基醇与丙二腈衍生的酰咪酯偶联反应可得到双恶唑啉环体系的不对称催化剂，并以苯甲醛与二乙基锌的烷基化反应为基础，考察了其作为手性催化剂的活性。因此，该反应在约40% ee中进行。用格氏试剂和NaBH_4连续处理l -酒石酸制备的c_2对称亚胺，可获得高选择性手性酰胺醇的可分离非对映混合物。以这些酰胺醇为催化剂，研究了与二乙基锌的不对称烷基化反应，结果如下：(1)增加n取代基的空间体积会导致对映体选择性的增加。(2)催化剂最大可循环18.8次。(3) （4S）型催化剂的选择性更高。(4)为了提高选择性，醚比甲苯更适合作为溶剂。此外，由d -阿拉伯糖铀糖衍生的环酰胺也可进行相同类型的手性催化反应。有趣的是，目前还没有采用环酰胺酰胺醇作为手性催化剂与二乙基锌进行不对称反应的方法。除了这些反应之外，抗生素(-)-大霉素和(+)-preussin的不对称全合成是通过立体选择亲核加成和不对称脱氧的羟基内酰胺中间体来完成的，这些中间体是由相同的原料阿拉伯糖铀糖合成的。13EA09：综上所述，制备了两种新型手性配体，并对其催化活性进行了研究，合成了两种抗生素天然产物。

项目成果

Hidemi Yoda: "Diastereoselective Reactions of Grignard Reagents with Chiral Amino Lactols Derived from L-Aspartic Acid" Tetrahedron: Asymmetry. 5. 169-172 (1994)

Hidemi Yoda：“格氏试剂与 L-天冬氨酸衍生的手性氨基乳醇的非对映选择性反应”四面体：不对称性。

Hidemi Yoda: "A Short Synthetic Approach to Enaxtiomerically Pure (-)-Anisomycin" Heterocycles. 41. 2423-2426 (1995)

Hidemi Yoda：“对映体纯 (-)-茴香霉素”杂环化合物的简短合成方法。

Hidemi Yoda: "Diastereo selective Reactions of Gngnard Reagents with Chiral Amino Lactols Deriued from L-Aspartic Acid" Tetrahedron:Asymmetry. 5. 169-172 (1994)

Hidemi Yoda：“Gngnard 试剂与 L-天冬氨酸衍生的手性氨基乳醇的非对映选择性反应”四面体：不对称性。

Hidemi Yoda: "A Novel Stereoselective Synthesis of Enantiomerically Pure Antifungal Agent, (+)-Preussin" Tetrahedron: Asymmetry. (in press).

Hidemi Yoda：“一种新型立体选择性合成对映体纯抗真菌剂，( )-Preussin”四面体：不对称性。

Hidemi Yoda: "Diastereoselective Reaction of Grignard Reagents with Chiral Amino Lactols Derived from L-Aspartic Acid" Tetrahedron : Asymmetry. 5. 169-172 (1994)

Hidemi Yoda：“格氏试剂与 L-天冬氨酸衍生的手性氨基乳醇的非对映选择性反应”四面体：不对称性。