Development of SpiroBipyridine Ligands for Efficient and Selective C-H Activation

• Project Area: Digitalization-driven Transformative Organic Synthesis (Digi-TOS)
• Project/Area Number: 22H05384
• Research Category: Grant-in-Aid for Transformative Research Areas (A)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (II)
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: イリエシュ ラウレアン 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, チームリーダー (40569951)
• Project Period (FY): 2022-06-16 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2023: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2022: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: organic synthesis / 有機合成

Outline of Research at the Start

Direct functionalization of simple or complex organic molecules is the most straightforward method to create new chemical space, but these reactions suffer limitations regarding efficiency and selectivity. I plan to use conceptually new spirobipyridine ligands and the power of machine learning to unlock a general strategy to functionalize a target C-H bond in a stoichiometric amount of a simple or complex arene under mild conditions and regio- and chemoselectively.

Outline of Annual Research Achievements

The purpose of this research is the development of new spirobipyridine ligands and of reaction conditions for the efficient and site-selective catalytic functionalization of arenes. During FY2023, we performed a mechanistic study by computations and an unprecedented ligand kinetic isotope effect to prove that a noncovalent interaction between a C-H bond of the spirobipyridine ligand's backbone and the pi electrons of the arene substrate can accelerate the iridium-catalyzed activation of arenes.
We also developed spirobipyridine ligands bearing hydroxyl (OH) groups capable of recognizing pyridine substrates through hydrogen bonding, and both accelerate and control the site selectivity in iridium-catalyzed borylation.
Finally, we developed a spirobipyridine ligand that enables meta-selective iridium-catalyzed silylation of monosubstituted arenes.

Research Progress Status

令和5年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和5年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] National Institute of Material Physics(ルーマニア)
• [Journal Article] Noncovalent interaction with a spirobipyridine ligand enables efficient iridium-catalyzed C-H activation (2024)
  • Author(s): Jin Yushu、Ramadoss Boobalan、Asako Sobi、Ilies Laurean
  • Journal Title: Nature Communications Volume: 15 Issue: 1 Pages: 2886-2886
  • DOI: 10.1038/s41467-024-46893-6
  • Peer Reviewed / Open Access
• [Journal Article] Remote Steric Control for Site-Selective Synthesis (2023)
  • Author(s): Asako Sobi、Ilies Laurean
  • Journal Title: Synlett Volume: 34 Issue: 18 Pages: 2110-2116
  • DOI: 10.1055/a-2126-1835
  • Peer Reviewed
• [Journal Article] Synthesis of 2,2′-Bipyridines via Dehydrogenative Dimerization of Pyridines Using Sodium Dispersion (2023)
  • Author(s): De Pinaki Bhusan、 Ilies Laurean、Takai Kazuhiko、Asako Sobi
  • Journal Title: Synlett Volume: 2023 Issue: 04 Pages: 459-463
  • DOI: 10.1055/a-2047-8355
  • Peer Reviewed
• [Journal Article] Molybdenum-Quinone-Catalyzed Deoxygenative Coupling of Aromatic Carbonyl Compounds (2022)
  • Author(s): Banerjee Somsuvra、Kobayashi Takafumi、Takai Kazuhiko、Asako Sobi、Ilies Laurean
  • Journal Title: Organic Letters Volume: 24 Issue: 39 Pages: 7242-7246
  • DOI: 10.1021/acs.orglett.2c03143
  • Peer Reviewed
• [Presentation] Substrate Recognition and Reaction Control by Functional Spirobipyridines (2024)
  • Author(s): Asako Sobi, Jin Yushu, Ramadoss Boobalan, De Bhusan Pinaki, Ilies Laurean
  • Organizer: CEMS International Symposium on Supramolecular Chemistry and Functional Materials 2024
• [Presentation] Remote Regiocontrol in Iridium-Catalyzed C-H Silylation of Arenes Enabled by SpiroBipyridine Ligand (2024)
  • Author(s): Jin Yushu, Sekar Jayakumar, Asako Sobi, Ilies Laurean
  • Organizer: The 104th CSJ Annual Meeting
• [Presentation] Ligand-Enabled Iridium-Catalyzed Regiodivergent C-H Borylation of Pyridines and Quinolines (2024)
  • Author(s): De Bhusan Pinaki, Okamoto Kazuhiro, Asako Sobi, Ilies Laurean
  • Organizer: The 104th CSJ Annual Meeting
• [Presentation] Development of catalytic systems for selective organic transformations (2023)
  • Author(s): Laurean Ilies
  • Organizer: Smart Diaspora 2023, Exploratory Workshop: Transboundary Chemistry at the Forefront of Molecular Sciences
  • Int'l Joint Research / Invited
• [Presentation] Catalyst Design for Selective and Efficient Reactions (2023)
  • Author(s): Laurean Ilies
  • Organizer: Seminar on Organic Molecule Transformations of Institute for Chemical Research, Kyoto University
  • Invited
• [Presentation] Catalyst-Enabled Selective Functionalization of Arenes (2023)
  • Author(s): Laurean Ilies
  • Organizer: Tateshina Conference on Organic Chemistry
• [Presentation] Design of New Ligands for Selective & Efficient Catalytic Transformations (2023)
  • Author(s): Laurean Ilies
  • Organizer: International Virtual Conference on “Recent Trends in Organometallics and Material Science"
  • Int'l Joint Research / Invited
• [Presentation] Ligand Design for Regioselective C-H Activation (2023)
  • Author(s): Laurean Ilies
  • Organizer: The 22nd European Symposium on Organic Chemistry
  • Int'l Joint Research / Invited
• [Presentation] My Research Journey in Japan (2023)
  • Author(s): Laurean Ilies
  • Organizer: Seminar of the Faculty of Chemistry and Chemical Engineering, Babes-Bolyai University
  • Int'l Joint Research / Invited
• [Presentation] Spirobipyridine Ligand for Remote Steric Control in Iridium-Catalyzed C-H Borylation of Arenes (2023)
  • Author(s): Asako Sobi, Jin Yushu, Ramadoss Boobalan, Ilies Laurean
  • Organizer: 21st International Symposium on Organometallic Chemistry Directed Toward Organic Synthesis
  • Int'l Joint Research
• [Presentation] スピロビピリジン：イリジウム触媒によるC-Hホウ素化反応における遠隔位立体制御および反応加速 (2023)
  • Author(s): Asako Sobi, Jin Yushu, Ramadoss Boobalan, Ilies Laurean
  • Organizer: 第33回基礎有機化学討論会
• [Presentation] Iridium-Catalyzed Regioswitchable C-H Borylation Enabled by Hydroxyspirobipyridine Ligands (2023)
  • Author(s): Pinaki Bhusan De, Kazuhiro Okamoto, Sobi Asako, Laurean Ilies
  • Organizer: The 69th Symposium on Organometallic Chemistry
• [Presentation] Catalyst Design for Selective and Efficient Reactions (2023)
  • Author(s): Laurean Ilies
  • Organizer: 第16回ChemBioハイブリッドレクチャー
  • Invited
• [Presentation] Remote steric control and acceleration in iridium-catalyzed C-H borylation of arenes enabled by spirobipyridine ligand (2023)
  • Author(s): Asako Sobi, Jin Yushu, Ramadoss Boobalan, Ilies Laurean
  • Organizer: The XXIII International Conference on Organic Synthesis
  • Int'l Joint Research
• [Presentation] 配位子設計による選択的なC-H結合変換反応の開発 (2023)
  • Author(s): Laurean Ilies
  • Organizer: 近畿化学協会有機金属部会第3回例会
  • Invited
• [Presentation] Spirobipyridine Enables Remote Steric Control and Rate Acceleration in Iridium-Catalyzed Aromatic C-H Borylation (2023)
  • Author(s): Asako Sobi, Jin Yushu, Ramadoss Boobalan, Ilies Laurean
  • Organizer: The 15th International Kyoto Conference on New Aspects of Organic Chemistry
  • Int'l Joint Research
• [Presentation] Catalyst Design for Selectivity and Reactivity (2023)
  • Author(s): Laurean Ilies
  • Organizer: Seminar of the Faculty of Chemistry, University of Bucharest
  • Int'l Joint Research / Invited
• [Presentation] Catalyst Design for Selectivity and Reactivity (2023)
  • Author(s): Laurean Ilies
  • Organizer: Seminar of the National Institute of Material Physics, Magurele
  • Int'l Joint Research / Invited
• [Presentation] Remote Substrate Recognition for Selectivity and Reactivity (2023)
  • Author(s): Laurean Ilies
  • Organizer: International Joint Symposium 2023 on Synthetic Organic Chemistry
• [Presentation] 触媒設計による選択的・効率的な合成反応の開発 (2023)
  • Author(s): Laurean Ilies
  • Organizer: 理研シンポジウム 「第 21 回 分析・解析技術と化学の最先端」
  • Invited
• [Presentation] Molybdenum-Catalyzed Directed Activation of Aromatic C-Cl and C-F Bonds (2023)
  • Author(s): Banerjee Somsuvra, Matsushita Naoki, Asako Sobi, Ilies Laurean
  • Organizer: The 103rd CSJ Annual Meeting
• [Presentation] 鉄触媒による有機ナトリウム化合物のカップリング反応 (2023)
  • Author(s): 高橋 一光，浅子 壮美，イリエシュ ラウレアン
  • Organizer: 日本化学会第103春季年会
• [Presentation] ナトリウム分散体を駆使する有機合成 (2022)
  • Author(s): 高橋一光, 中島啓貴, イリエシュ ラウレアン, 浅子壮美, 高井和彦
  • Organizer: 第11回 JACI/GSCシンポジウム
• [Presentation] イリジウム-スピロビピリジン触媒による芳香族炭化水素のメタ位選択的ホウ素化反応および反応加速 (2022)
  • Author(s): 浅子壮美，金玉樹，ラマドス ブーバラン，イリエシュ ラウレアン
  • Organizer: 日本プロセス化学会2022サマーシンポジウム
• [Presentation] Spirobipyridine Enables Remote Steric Control and Rate Enhancement in Iridium-Catalyzed C-H Borylation of Arenes (2022)
  • Author(s): Asako Sobi, Jin Yushu, Ramadoss Boobalan, Ilies Laurean
  • Organizer: The 15th International Conference on Cutting-Edge Organic Chemistry in Asia
  • Int'l Joint Research / Invited
• [Presentation] スピロビピリジン：イリジウム触媒による炭素-水素結合ホウ素化反応における遠隔位立体制御および反応促進 (2022)
  • Author(s): 浅子 壮美, 金 玉樹, Boobalan Ramadoss, Laurean Ilies
  • Organizer: 第68回有機金属化学討論会
• [Presentation] モリブデン触媒によるカルボニル化合物の脱酸素カップリングを経るオレフィン合成 (2022)
  • Author(s): Somsuvra Banerjee, 小林 嵩史, 髙井 和彦, 浅子 壮美, Laurean Ilies
  • Organizer: 第68回有機金属化学討論会
• [Presentation] SpiroBipyridine Ligands for Catalytic C-H Functionalization (2022)
  • Author(s): Ilies Laurean
  • Organizer: The 11th Singapore International Chemistry Conference
  • Int'l Joint Research / Invited
• [Presentation] Design of New Ligands for Selective C-H Functionalization (2022)
  • Author(s): Ilies Laurean
  • Organizer: Tateshina Conference on Organic Chemistry
  • Invited
• [Presentation] Organic Synthesis Using Organosodium Compounds (2022)
  • Author(s): Asako Sobi, Takahashi Ikko, Takai Kazuhiko, Ilies Laurean
  • Organizer: International Symposium on Innovative Reactions through Controlling Electrons
  • Int'l Joint Research
• [Presentation] Spirobipyridine Ligand for Remote Steric Control and Rate Enhancement in Iridium-Catalyzed C-H Borylation of Arenes (2022)
  • Author(s): Asako Sobi, Jin Yushu, Ramadoss Boobalan, Ilies Laurean
  • Organizer: 第12回サブウェイセミナー
• [Book] Handbook of CH-Functionalization (2022)
  • Author(s): Asako Sobi, Ilies Laurean
  • Total Pages: 8152
  • Publisher: Wiley
  • ISBN: 9783527834242
• [Remarks] “弱い相互作用”で炭化水素資源の変換反応を大きく加速
  • URL: https://www.riken.jp/press/2024/20240417_4/index.html
• [Remarks] Ilies Team Home Page
  • URL: http://iliesteam.riken.jp/home.html
• [Remarks] Advanced organic synthesis research team HP
  • URL: http://iliesteam.riken.jp/home.html