Design of a Chiral Dinucleating System Utilizing Tartaric Acid Ester as a Chiral Auxiliary and Its Application to the Synthesis of Optically Active Compounds

以酒石酸酯为手性助剂的手性双核体系设计及其在光学活性化合物合成中的应用

• 批准号: 10640515
• 负责人: UKAJI Yutaka
• 金额: $ 2.5万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10640515/
• 关键词: dinucleating; tartaric acid ester; chiral; 1,3-dipolar cycloaddition reaction; nitrile oxide; 2-isoxazoline; Reformatsky-type reagent; β-amino acid; β-アミノ酸誘導体; 亜鉛; マグネシウム; 水; エステルエノラート

It is strongly required to develop a practical and efficient method for the construction of chiral molecules to explore new biologically active medicines and agricultural chemicals. In this research, a new and novel chiral system possessing two metal centers utilizing tartaric acid esters was designed ; that is, if two reactants are bound to two different metal centers of the dialkoxide derived from tartaric acid ester, which might actually form the rigid 5/5-fused bicyclic dinucleating structure, they might be ideally oriented and/or activated by the metals and the following reaction might proceed in an enantioselective manner to afford the corresponding optically active products.The asymmetric 1,3-dipolar cycloaddition of nitrile oxides to ethyl (E)-4-hydroxy-2-butenoate was achieved by the use of diisopropyl (R,R)-tartrate as a chiral auxiliary to afford the corresponding 4,5-trans-2-isoxazolines, which were transformed to the corresponding 4,5-cis-2-isoxazolines by the treatment with a base through isomerization and lactonization.The asymmetric addition of the Reformatsky-type reagent, prepared in situ from diethylzinc and iodoacetic acid ester, to a carbon-nitrogen double bond in 3,4-dihydroisoquinoline N-oxides was achieved with enantioselectivity up to 86% ee. Furthermore, the asymmetric addition of the Reformatsky-type reagent to imines prepared from aldehydes and 2-aminophenol was also achieved to give β-amino acid derivatives. In order to realize reproducible higher stereoselection, the addition of a small amount of water was crucial.

开发实用、高效的手性分子构建方法是开发新型生物活性药物和农药的迫切需要。本研究设计了一种新颖的酒石酸酯手性双金属中心体系;也就是说，如果两种反应物与衍生自酒石酸酯的二烷氧基化合物的两个不同的金属中心结合，这实际上可能形成刚性5/5-稠合双环双核结构，它们可以被金属理想地定向和/或活化，并且随后的反应可以以对映选择性的方式进行以提供相应的光学活性产物。以（R，R）-酒石酸二异丙酯为手性助剂，实现了氧化腈与（E）-4-羟基-2-丁烯酸乙酯的3-偶极环加成反应，得到相应的4，5-反式-2-异恶唑啉，再经碱处理，通过异构化和内酯化反应，得到相应的4，5-顺式-2-异恶唑啉。以二乙基锌和碘乙酸酯为原料，原位合成了Reformatsky型试剂，该试剂与3，4-二氢异喹啉N-氧化物中的碳氮双键发生不对称加成反应，对映选择性高达86%ee，并与醛和2-氨基苯酚反应生成的亚胺进行了不对称加成反应，得到了β-氨基酸衍生物.为了实现可再现的更高立体选择性，添加少量水是至关重要的。

项目成果

K. Inomata: "Development of the Asymmetric Cycloaddition Reactions and Asymmetric Nucleophilic Addition Reaction Utilizing Tartaric Acid Ester"J. Synth. Org. Chem. Jpn.. 56. 11-21 (1998)

K. Inomata：“利用酒石酸酯开发不对称环加成反应和不对称亲核加成反应”J。

K. Inomata: "Development of New Asymmetric Reactions Utilizing Tartaric Acid Ester as a Chiral Auxiliary : Design of an Efficient Chiral Dinucleating System"Reviews on Heteroatom Chemistry. 18. 119-140 (1998)

K. Inomata：“利用酒石酸酯作为手性助剂开发新的不对称反应：高效手性双核系统的设计”杂原子化学评论。

Y.Yoshida, Y.Ukaji, S.Fujinami, and K.Inomata: "Asymmetric 1,3-Dipolar Cycloaddition of Nitrile Oxides to γ-Substituted Allylic Alcohols" Chem.Lett.,. 1998. 1023-1024 (1998)

Y.Yoshida、Y.Ukaji、S.Fujinami 和 K.Inomata：“腈氧化物与 γ-取代烯丙醇的不对称 1,3-偶极环加成”Chem.Lett.，1998。1023-1024 (1998)

Y. Ukaji: "Asymmetric Addition of the Reformatsky-Type Reagent to 3,4-Dihydroisoquinoline N-Oxides"Tetrahedron : Asymmetry. (in press).

Y. Ukaji：“Reformatsky 型试剂对 3,4-二氢异喹啉 N-氧化物的不对称加成”四面体：不对称性。

Y. Yoshida: "Asymmetric 1,3-Dipolar Cycloaddition of Nitrile Oxides to γ-Substituted Allylic Alcohols"Chem. Lett.. 1023-1024 (1998)

Y. Yoshida：“氧化腈与 γ-取代烯丙醇的不对称 1,3-偶极环加成”Chem. Lett. 1023-1024 (1998)