Development of Bifunctional Ligands for Efficient Selective Activation of Simple Arenes

开发用于有效选择性激活简单芳烃的双功能配体

基本信息

批准号：
22K14689
负责人：
金玉樹
金额：
$ 2.91万
依托单位：
Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Early-Career Scientists
财政年份：
2022
资助国家：
日本
起止时间：
2022-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K14689/
关键词：
ligand design C-H activation borylation iridium spirobipyridine selectivity Synthetic Chemistry C-H Activation Ligand Design Organic Synthesis

项目摘要

In this research, a novel “roof” ligand Bpin-SpiroBpy was developed for the meta-selective C-H activation of simple arenes. This concept was proved by iridium-catalyzed C-H borylation reaction of various kinds of mono-substituted arenes, in which the “roof” sterically protects the remotest para site besides the ortho site to achieve meta-selective C-H activation in the iridium-catalyzed borylation. The strategy proved general, and a variety of monosubstituted arenes including alkylbenzenes, anilines, protected-phenols, and drug molecules could be selectively borylated at the meta position in both high yields and selectivity. The choice of “roof” also appeared to be important. It was found that the rigidness of Bpin group on the three-dimensionally expanded SpiroBpy ligand effectively created a molecular pocket that accommodates the substrate approaching the catalytic center only in the meta orientation.In the following investigations, it was found that the iridium C-H borylation of electron-rich arenes was largely boosted by employing SpiroBpy as the ligand. When electron-rich arenes such as 1,3-dimethoxybenzene and 1,3-di-tert-butylbenzene were used as the substrate for the iridium-catalyzed C-H borylation with HBpin, the borylated product was obtained in high yields by using SpiroBpy as the ligand. In contrast, the borylation proceeded in lower yields with the commonly used ligands (dtbpy or tmphen) under similar conditions. This method is expected to expand the toolbox of this reaction to more diverse applications.

在这项研究中，开发了一种新型“屋顶”配体Bpin-SpiroBpy，用于简单芳烃的间位选择性C-H活化，这一概念通过各种单取代芳烃的铱催化C-H硼化反应得到了证明，其中“ “屋顶”在空间上保护除邻位点之外的最远的对位点，以实现铱催化硼化反应中的元选择性C-H激活。该策略得到了证明。一般而言，各种单取代芳烃，包括烷基苯、苯胺、受保护的酚和药物分子，都可以在间位选择性硼基化，同时具有高产率和选择性。“屋顶”的选择似乎也很重要。三维扩展的SpiroBpy配体上Bpin基团的刚性有效地创建了一个分子口袋，仅在间位方向上容纳接近催化中心的底物。在接下来的研究中，发现当使用富电子芳烃如1,3-二甲氧基苯和1,3-二叔丁基苯作为底物时，富电子芳烃的铱C-H硼化反应通过使用SpiroBpy作为配体而得到极大促进。以SpiroBpy为配体，在铱催化下用HBpin进行C-H硼化，得到了高产率的硼化产物。在相似的条件下，使用常用配体（dtbpy 或 tmphen）进行硼化反应的产率较低，该方法有望将该反应的工具箱扩展到更多样化的应用。