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，开发了一种新型的“屋顶”配体Bpin-spirobpy，用于简单舞台的元选择性C-H激活。这一概念是通过虹膜催化的各种单一取代的领域的C-H型体现反应证明的，其中“屋顶”在空间外保护了远程para位点以外的位点，以实现虹膜诱导的元素诱导的Borylation的元选择性C-H激活。该策略被证明是一般的，可以在高产量和选择性的元位置上选择性地将多种单卜生的领域在元位置选择性地植入，包括烷基苯甲酸，苯胺，受保护的酚和药物分子。 “屋顶”的选择似乎也很重要。发现BPIN组在三维扩展的螺旋体配体上的刚性有效地创建了一个分子袋，该袋仅适用于元方向接近催化中心的基材。在以下研究中，发现通过使用Electon-rich的虹膜C-H Borytium C-H Borylation通过使用Spiperby来实现Electron-rich rach的Boriged boosted。当用富含电子的领域（例如1,3-二甲氧基苯苯和1,3-二甲基丁基苯苯用作iridium催化的C-H Borylation的底物）用HBPIN的底物，使用螺旋体作为配体以高收益率以高收率获得了型型产物。相比之下，在相似条件下，具有较低的种植体（dtbpy或tmphen）以较低的产率进行。预计该方法将将这种反应的工具箱扩展到更多的潜水应用程序。