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

基本信息

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

项目摘要

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，通过2当量的手性氨基醇与丙二腈衍生的亚氨酸酯的偶联反应可以得到双恶唑啉环系的不对称催化剂，并基于苯甲醛的烷基化研究了其作为手性催化剂的活性与二乙基锌。因此，该反应以约 40% ee.2 进行。用格氏试剂和NaBH_4连续处理由L-酒石酸制备的C_2-对称酰亚胺，以高选择性提供可分离的手性酰胺醇的非对映混合物。以这些酰胺醇为催化剂，研究了二乙基锌的不对称烷基化反应，结果如下：（1）增加N-取代基的空间体积导致对映选择性的增加。（2）催化剂最大循环次数为18.8次。 (3)在(4S)-构型的催化剂的情况下获得了更高的选择性。(4)为了提高选择性，乙醚优于甲苯作为催化剂此外，衍生自D-阿拉伯呋喃糖的环酰胺也进行了相同类型的手性催化反应。有趣的是，目前还没有出现以环酰胺的酰胺醇等为手性催化剂与二乙基锌进行不对称反应的方法。 3．除了这些反应之外，还利用立体选择性亲核加成和由相同起始材料阿拉伯呋喃糖制成的羟基内酰胺中间体的不对称脱氧，完成了抗生素、(-)-茴香霉素和(+)-普鲁素的不对称全合成。 13EA09：总结制备并研究了两种新型手性配体的催化活性，并合成了两种抗生素天然产物。