| 研究課題/領域番号 |
22K14689
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分33020:有機合成化学関連
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| 研究機関 | 国立研究開発法人理化学研究所 |
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研究代表者 |
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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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,550千円 (直接経費: 3,500千円、間接経費: 1,050千円)
2023年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
2022年度: 2,470千円 (直接経費: 1,900千円、間接経費: 570千円)
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| キーワード | ligand design / C-H activation / borylation / iridium / spirobipyridine / selectivity / silylation / Synthetic Chemistry / C-H Activation / Ligand Design / Organic Synthesis |
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| 研究開始時の研究の概要 |
Efficient selective organic synthesis is highly demanded and valuable in modern synthetic chemistry. However, recognizing specific position is still challenging. Here, a biomimetic concept inspired bifunctional ligand is designed to enable efficient selective activation of simple arenes. The concept of design based on utilizing the unexplored upper/down face of bipyridine moiety to install a second functional/recognition unit, which was linked to bipyridine with a quaternary carbon. The second unit could provide different functions, such as sterical hinderance, non-covalent interaction, etc.
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| 研究実績の概要 |
In this research, it was found that the iridium C-H borylation of electron-rich arenes was largely boosted by employing spirobipyridine (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. The results of DFT calculation indicated that a potential CH-pi interaction between the fluorene backbone of the SpiroBpy ligand and the arene substrate may be responsible for the acceleration. To prove this hypothesis, an octadeuterated ligand SpiroBpy-d8 was synthesized, and was employed to kinetic studies. The results showed an inverse ligand kinetic isotope effect, which means the reaction proceeded faster with the deuterated ligand. These results proved the involvement of CH-pi interaction in stabilization of the transition state. Overall, this method is expected to expand the toolbox of this reaction to more diverse applications.
In the following research, a newly designed “roof” SpiroBpy was synthesized, and was found to be useful for the iridium-catalyzed meta-selective C-H silylation reactions. The two substituents adjacent to the N atoms was found to be critical to achieve high yield. Various mono-substituted arenes could be selectively silylated at their meta-postions to achieve up to 36:1 meta-selectivity.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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. The results were already published in a top journal. In the second year, a boosting effect of the C-H borylation was discovered in the following investigations. Optimization of the ligand and reaction conditions, substrate scope (comparison with dtbpy and tmphen ligands), application to late-stage functionalization of pharmaceutically relevant compounds, and mechanistic studies were accomplished as scheduled. This project is also completed and recently published in another top journal. Furthermore, recently a new project just started by the successful synthesis of a newly designed “roof” SpiroBpy ligand. This ligand allowed iridium-catalyzed meta-selective C-H silylation of mono-substituted arenes. Detailed investigations on this new project are ongoing now. Overall, the current research is progressing as scheduled, and have good chance to achieve more exciting findings in the future.
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| 今後の研究の推進方策 |
In the following research, several related projects will be investigated.
Firstly, it is necessary to complete the substrate scope, synthetic applications, and mechanistic investigations for the iridium-catalyzed meta-selective C-H silylation of mono-substituted arenes using new “roof” SpiroBpy ligand. Computational investigations will also be conducted for this project to reveal the mechanistic insights.
Next, synthesis and development of pincer-type SpiroBpy ligands will be performed. A new NNSi-pincer type SpiroBpy ligands has recently been synthesized. It was found that the NNSi-pincer type SpiroBpy ligands was useful for the selective C-H borylation of fluorinated arene derivatives. Although the reason is unclear at this moment, the project has the potential to achieve unique selectivity for fluorinated arenes, which has never been reported before.
On the other hand, synthesis and development of the “umbrella-type” SpiroBpy ligands is also promising. The designed “umbrella” is expected to provide a finer molecular pocket, which would fit those small molecules in a more suitable fashion to achieve even higher meta-selectivity with small molecules, such as toluene.
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