2022 Fiscal Year Research-status Report
Development of Bifunctional Ligands for Efficient Selective Activation of Simple Arenes
| Project/Area Number |
22K14689
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
金 玉樹 国立研究開発法人理化学研究所, 環境資源科学研究センター, 特別研究員 (90909178)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | ligand design / C-H activation / borylation / iridium / spirobipyridine / selectivity |
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| Outline of Annual Research Achievements |
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.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The progress of this research is mostly as expected. In the first year, the meta-selective C-H borylation of simple arenes has been achieved. Optimization of the ligand and reaction conditions, substrate scope, and mechanistic studies were accomplished as scheduled. The results were already published in a top journal. In the following investigations, a boosting effect of the C-H borylation was discovered. This new project is still under investigation. Furthermore, a prototype of the 2nd generation of SpiroBpy ligand was already synthesized. According to the plan, the 2nd generation of SpiroBpy ligands will be subjected to the borylation of arenes with smaller substituents. Modification of the ligand structure will also be necessary. Overall, the current research is progressing as scheduled, and have good chance to achieve more and more new findings in the following year.
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| Strategy for Future Research Activity |
In the following research, several related projects will be investigated.
Firstly, it is necessary to complete the substrate scope, synthetic applications for the iridium-catalyzed C-H borylation of electron-rich arenes using SpiroBpy ligands. Furthermore, it would be more important to perform mechanistic studies to reveal the reason for this acceleration effect. Both experimental and computational investigations will be conducted for this project.
Next, synthesis and development of the 2nd generation SpiroBpy ligands will be performed. An “umbrella-type” SpiroBpy ligand will be synthesized for the meta-selective C-H borylation of mono-substituted arenes with small sterical hinderance, such as toluene, acetonitrile, etc. The designed “umbrella” is expected to provide a finer molecular pocket, which would fit those small molecules in a more suitable fashion.
On the other hand, it is also expected that a structurally modified SpiroBpy ligand would be useful for other reactions, such as selective C-H silylation, which has never been reported before.
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| Causes of Carryover |
A certain amount of research funds was prepared for purchasing chemical reagents, organic solvents, metal complexes and reaction vessels, etc. However, due to the covid situation, the research progress was somehow influenced. Also, attending domestic and international conferences was scheduled at the beginning. However, most of the conferences became online during the last fiscal year. Therefore, the budgets prepared for traveling were not used. The unconsumed research funds will be properly used within this fiscal year.
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