Development of Bifunctional Ligands for Efficient Selective Activation of Simple Arenes

在这项研究中，一种新型的“屋顶”配体Bpin-SpiroBpy被开发出来，用于简单芳烃的亚选择性C-H活化。各种单取代芳烃在Ir催化下的C-H硼化反应证实了这一观点，在该反应中，除了邻位外，“顶位”空间地保护了最远的对位，从而实现了在Ir催化的硼化反应中的超选择性C-H活化。该策略被证明是通用的，各种单取代芳烃，包括烷基苯、苯胺、受保护的苯酚和药物分子，都可以在间位上选择性地进行硼化反应，产率和选择性都很高。“屋顶”的选择似乎也很重要。研究发现，在三维扩展的SproBpy配体上，Bpin基团的刚性有效地形成了一个分子口袋，使底物仅在间位取向上接近催化中心。在随后的研究中，发现以SproBpy为配体可以很大程度上促进富电子芳烃的Ir C-H硼化反应。以1，3-二甲氧基苯和1，3-二叔丁基苯等富电子芳烃为底物，以螺环比为配体，高产率地催化了Hb与Ir的C-H硼化反应。相反，在类似的条件下，用常用的配体(dtbpy或tmphen)进行的硼化反应的产率较低。这种方法有望将这种反应的工具箱扩展到更多样化的应用领域。

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.