Synthesis of C2 Chiral Bidentate Diamine Ligands Derived from Macrocyclic Troger Base and Its Application to Asymmetric Synthesis

大环Troger碱衍生的C2手性二齿二胺配体的合成及其在不对称合成中的应用

• 批准号: 11640539
• 负责人: MIYAHARA Yuji
• 金额: $ 2.24万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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/grant/KAKENHI-PROJECT-11640539/
• 关键词: Troger base; optical resolution; transition metal complexes; 光学活性ジアミン; ジアミン配位子

We have succeeded in developing an efficient synthesis of a macrocyclic Troger base with a polyether tether (Trogarophane) by reacting triethylene glycol bis (p-aminophenyl) ether and formalin in HCl-EtOH solution at 80℃ for 18 h. Since the molecular cavity found to be too small for use as a cyclophane host, we turned to the outer dinitrogen moiety. It was expected that when the endo-methylene group is removed, the resulting diamine will become a promising bidentate ligand and, because the inversion is prohibited by the polyether tether, the C2 chiral properties of Troger base will be preserved. Removal of the endo-methylene bridge was not straightforward, because the ether oxygen made the already electron-rich benzene ring more reactive towards oxidixing agents. On successive treatments with trifluoroacetic anhydride and methanolic sodium carbonate the diNH compound was obtained. Methylation of one or both of the nitrogen atoms was completely controlled by suitable selection of the reaction conditions. The optical resolution of all the compounds was effectively accomplished by use of a chiral column (Chiralcel OJ) with increasing efficiency diNMe<NHNMe<Tr o gerophane<diNH.Although the separation for the diNH compound was really remarkable, for the reasons of wide applicability Tr o gerophane was mainly separated. It is gratifying that rather sparingly soluble racemic Trogerophane becomes very soluble on separation so that considerable amounts can be applied on the column with the use of cosolvent. Determination of the absolute structure of the separated Trogerophane is underway.Since the metal ion complexation was confirmed with several kinds of elements, we are currently examining the right conditions for asymmetric synthesis.

我们通过在80 h溶液中在HLCL-EtoH溶液中反应三乙二醇BIS（P-氨基磷）乙醚，成功地开发了与聚醚系线（Trogarophane）与聚醚系（Trogarophane）的有效合成的合成。由于发现分子腔太小，无法用作环粒宿主，因此我们转向了外部二氮部分。可以预期，当去除甲基甲基烯基团时，所得的二胺将成为应许的鸟类配体，并且由于聚醚束带禁止反转，因此将保留Troger碱基的C2手性特性。去除内甲基桥并不简单，因为醚氧使已经具有电子富含电子的苯环对氧化剂更具反应性。在用三氟乙酸酸酐和碳酸钠成功治疗时，获得了DINH化合物。一个或两个氮原子的甲基化通过适当选择反应条件完全控制。所有化合物的光学分辨率通过使用手性柱（Chiralcel OJ）有效地实现，而效率提高DINME <nHnMe <nhnme <nhnme <tr o gerophane <dinh。令人欣慰的是，相当多的固体外星型曲果烷在分离上变得非常固体，因此可以使用助质量将考虑量应用于圆柱上。分离的曲果磷烷的绝对结构的测定正在进行中。由于金属离子络合物已通过几种元素证实，我们目前正在研究不对称合成的正确条件。

项目成果

Y.Miyahara, K.Goto, T.Inazu: "A Novel Hindered Macrocyclic Tetramine Containing Two Bispidine UnitS : A New Type of Proton Sponge"Tetrahedron Letters. (in print). (2001)

Y.Miyahara、K.Goto、T.Inazu：“一种含有两个双吡啶单元的新型受阻大环四胺：一种新型质子海绵”四面体字母。