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

本文报道了一种以三甘醇双（对氨基苯基）醚和福尔马林为原料，在HCl-EtOH溶液中于80℃反应18 h，合成大环Troger碱的新方法。由于发现分子腔太小而不能用作环蕃主体，我们转向外部二氮部分。预期当去除内亚甲基基团时，所得二胺将成为有希望的双齿配体，并且由于聚醚系链禁止了反转，因此Troger碱的C2手性性质将被保留。去除内亚甲基桥并不简单，因为醚氧使已经富含电子的苯环对氧化剂更具反应性。用三氟乙酸酐和碳酸钠的甲醇溶液连续处理，得到二NH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。用手性柱（Chiralcel OJ）高效地完成了所有化合物的光学拆分，diNMe<NHNMe<Tr o gerophane<diNH，虽然对diNH化合物的分离确实很显著，但由于适用性广，主要分离Tr o gerophane。令人满意的是，相当微溶的外消旋Trogerophane在分离时变得非常可溶，使得可以使用共溶剂将相当大的量施加到柱上。分离出的Trogerophane的绝对结构的确定正在进行中。由于金属离子与多种元素的络合得到了确认，因此我们目前正在研究不对称合成的正确条件。

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.