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 |
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 |
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 – 2024-03-31
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研究課題ステータス |
交付 (2022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 / Synthetic Chemistry / C-H Activation / Ligand Design / Organic Synthesis |
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, 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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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. 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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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 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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