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Innovative mechanochemical synthesis for chemical transformations of insoluble organic compounds

Research Project

Project/Area Number 21H01926
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 33020:Synthetic organic chemistry-related
Research InstitutionHokkaido University

Principal Investigator

Kubota Koji  北海道大学, 工学研究院, 准教授 (60824828)

Co-Investigator(Kenkyū-buntansha) SIDOROV PAVEL  北海道大学, 化学反応創成研究拠点, 准教授 (30867619)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
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)
Fiscal Year 2021: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywordsボールミル / メカノケミストリー / 固体反応 / 不溶性化合物 / クロスカップリング反応 / クロスカップリング / データ科学 / メカノケミカル合成 / ナノグラフェン
Outline of Research at the Start

現代の有機合成化学では、基質を溶解させて合成反応を実施する必要があるため、必然的に適用可能な基質は、溶解性の良い単純な構造の分子群に限られてきた。しかし、近年求められている最先端有機機能性材料、発光材料や電子・ホール輸送材料の多くは、大きなπ共役骨格を有するものが多く、出発原料や合成中間体の低い溶解性がその開発を妨げてきた。本研究では、本研究代表者らが独自に開発した固体クロスカップリング反応と「加熱ボールミル法」を駆使することで、「溶解性問題」という100年近く続いた有機合成化学のボトルネックを解決する革新的な固体有機合成化学の確立を目指す。

Outline of Final Research Achievements

Conventional organic synthesis has been generally carried out in solution using organic solvents. However, in principle, this method cannot handle compounds that are insoluble in solvents. In this study, solid-state organic chemical reactions of various insoluble substrates were investigated by utilizing a mechanochemical method using a grinding machine called a ball mill. In this research period, the main results of this study include the development of highly efficient cross coupling reactions using transition metal catalysts that proceed in the solid state, the discovery of the acceleration effect of polymer addition on solid-state cross coupling of insoluble compounds, and the development of original catalysts specialized for solid-state cross coupling reactions. These results will contribute to further development of mechanochemical synthesis in the future.

Academic Significance and Societal Importance of the Research Achievements

近年求められている最先端有機機能性材料、発光材料や電子・ホール輸送材料の多くは、大きなπ共役骨格を有するものが多く、出発原料や合成中間体の低い溶解性がその開発を妨げてきた。本研究では、本研究代表者らが独自に開発した固体クロスカップリング反応を駆使することで、「溶解性問題」という100年近く続いた有機合成化学のボトルネックを解決する革新的な固体有機合成化学の基盤となる成果を得ることができた。本研究課題の遂行により、メカノケミカル合成が人類が手にしたことのなかった未踏有機分子群へのアクセスを可能とする実用的な方法であることが示された。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (45 results)

All 2024 2023 2022 2021

All Journal Article (23 results) (of which Peer Reviewed: 23 results,  Open Access: 6 results) Presentation (22 results) (of which Int'l Joint Research: 8 results,  Invited: 19 results)

  • [Journal Article] Mechanochemistry enabling highly efficient Birch reduction using sodium lumps and D-(+)-glucose2024

    • Author(s)
      Kondo Keisuke、Kubota Koji、Ito Hajime
    • Journal Title

      Chemical Science

      Volume: 15 Issue: 12 Pages: 4452-4457

    • DOI

      10.1039/d3sc06052g

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Solid-state mechanochemistry for the rapid and efficient synthesis of tris-cyclometalated iridium(III) complexes2024

    • Author(s)
      Kubota Koji、Endo Tsubura、Ito Hajime
    • Journal Title

      Chemical Science

      Volume: 15 Issue: 9 Pages: 3365-3371

    • DOI

      10.1039/d3sc05796h

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ring Expansion of Cyclic Boronates via Oxyboration of Arynes2024

    • Author(s)
      Shiratori Yuma、Jiang Julong、Kubota Koji、Maeda Satoshi、Ito Hajime
    • Journal Title

      Journal of the American Chemical Society

      Volume: 146 Issue: 3 Pages: 1765-1770

    • DOI

      10.1021/jacs.3c11851

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Using Mechanochemistry to Activate Commodity Plastics as Initiators for Radical Chain Reactions of Small Organic Molecules2023

    • Author(s)
      Kubota Koji、Jiang Julong、Kamakura Yuri、Hisazumi Reon、Endo Tsubura、Miura Daiyo、Kubo Shotaro、Maeda Satoshi、Ito Hajime
    • Journal Title

      Journal of the American Chemical Society

      Volume: 146 Issue: 1 Pages: 1062-1070

    • DOI

      10.1021/jacs.3c12049

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Solid-state mechanochemical cross-coupling of insoluble substrates into insoluble products by removable solubilizing silyl groups: uniform synthesis of nonsubstituted linear oligothiophenes2023

    • Author(s)
      Kubota Koji、Kondo Keisuke、Seo Tamae、Jin Mingoo、Ito Hajime
    • Journal Title

      RSC Advances

      Volume: 13 Issue: 41 Pages: 28652-28657

    • DOI

      10.1039/d3ra05571j

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stereospecific synthesis of silicon-stereogenic optically active silylboranes and general synthesis of chiral silyl Anions2023

    • Author(s)
      Wang Xihong、Feng Chi、Jiang Julong、Maeda Satoshi、Kubota Koji、Ito Hajime
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 5561-5561

    • DOI

      10.1038/s41467-023-41113-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual Nickel(II)/Mechanoredox Catalysis: Mechanical‐Force‐Driven Aryl‐Amination Reactions Using Ball Milling and Piezoelectric Materials2023

    • Author(s)
      Seo Tamae、Kubota Koji、Ito Hajime
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 62 Issue: 42

    • DOI

      10.1002/anie.202311531

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An Improved Catalytic System for Solid-state Iridium(I)-catalyzed C-H Borylation Using Mechanochemistry2023

    • Author(s)
      Kondo Keisuke、Ishiyama Tatsuo、Kubota Koji、Ito Hajime
    • Journal Title

      Chemistry Letters

      Volume: 52 Issue: 5 Pages: 333-336

    • DOI

      10.1246/cl.230081

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanochemical Approach for Air‐Tolerant and Extremely Fast Lithium‐Based Birch Reductions in Minutes2023

    • Author(s)
      Gao Yunpeng、Kubota Koji、Ito Hajime
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 62 Issue: 21

    • DOI

      10.1002/anie.202217723

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanochemistry-Directed Ligand Design: Development of a High-Performance Phosphine Ligand for Palladium-Catalyzed Mechanochemical Organoboron Cross-Coupling2023

    • Author(s)
      Seo Tamae、Kubota Koji、Ito Hajime
    • Journal Title

      Journal of the American Chemical Society

      Volume: 145 Issue: 12 Pages: 6823-6837

    • DOI

      10.1021/jacs.2c13543

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Solid-state Silver-catalyzed Ring-opening Fluorination of Cyclobutanols Using Mechanochemistry2023

    • Author(s)
      Isshiki Ryota、Kubota Koji、Ito Hajime
    • Journal Title

      Synlett

      Volume: - Issue: 12 Pages: 1419-1424

    • DOI

      10.1055/a-2021-9599

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Solid-state cross-coupling reactions of insoluble aryl halides under polymer-assisted grinding conditions2023

    • Author(s)
      Kubota Koji、Seo Tamae、Ito Hajime
    • Journal Title

      Faraday Discussions

      Volume: 241 Pages: 104-113

    • DOI

      10.1039/d2fd00121g

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanochemical protocol facilitates the generation of arylmanganese nucleophiles from unactivated manganese metal2023

    • Author(s)
      Takahashi Rina、Gao Pan、Kubota Koji、Ito Hajime
    • Journal Title

      Chemical Science

      Volume: 14 Issue: 3 Pages: 499-505

    • DOI

      10.1039/d2sc05468j

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry2022

    • Author(s)
      Kubota Koji、Baba Emiru、Seo Tamae、Ishiyama Tatsuo、Ito Hajime
    • Journal Title

      Beilstein Journal of Organic Chemistry

      Volume: 18 Pages: 855-862

    • DOI

      10.3762/bjoc.18.86

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanochemically Generated Calcium‐Based Heavy Grignard Reagents and Their Application to Carbon-Carbon Bond‐Forming Reactions2022

    • Author(s)
      Gao Pan、Jiang Julong、Maeda Satoshi、Kubota Koji、Ito Hajime
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 61 Issue: 41

    • DOI

      10.1002/anie.202207118

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insight into the Reactivity Profile of Solid-State Aryl Bromides in Suzuki-Miyaura Cross-Coupling Reactions Using Ball Milling2022

    • Author(s)
      Kubota Koji、Ito Hajime、Kondo Keisuke、Seo Tamae
    • Journal Title

      Synlett

      Volume: - Issue: 09 Pages: 898-902

    • DOI

      10.1055/a-1748-3797

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient access to materials-oriented aromatic alkynes via the mechanochemical Sonogashira coupling of solid aryl halides with large polycyclic conjugated systems2022

    • Author(s)
      Gao Yunpeng、Feng Chi、Seo Tamae、Kubota Koji、Ito Hajime
    • Journal Title

      Chemical Science

      Volume: 13 Issue: 2 Pages: 430-438

    • DOI

      10.1039/d1sc05257h

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Solid‐State C-N Cross‐Coupling Reactions with Carbazoles as Nitrogen Nucleophiles Using Mechanochemistry2021

    • Author(s)
      Kubota Koji、Endo Tsubura、Uesugi Minami、Hayashi Yuta、Ito Hajime
    • Journal Title

      ChemSusChem

      Volume: 15 Issue: 2

    • DOI

      10.1002/cssc.202102132

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Palladium-Catalyzed Solid-State Polyfluoroarylation of Aryl Halides Using Mechanochemistry2021

    • Author(s)
      Takahashi Rikuro、Seo Tamae、Kubota Koji、Ito Hajime
    • Journal Title

      ACS Catalysis

      Volume: 11 Issue: 24 Pages: 14803-14810

    • DOI

      10.1021/acscatal.1c03731

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanochemical synthesis of magnesium-based carbon nucleophiles in air and their use in organic synthesis2021

    • Author(s)
      Takahashi Rina、Hu Anqi、Gao Pan、Gao Yunpeng、Pang Yadong、Seo Tamae、Jiang Julong、Maeda Satoshi、Takaya Hikaru、Kubota Koji、Ito Hajime
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 6691-6691

    • DOI

      10.1038/s41467-021-26962-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of hydrosilylboronates via the monoborylation of a dihydrosilane Si?H bond and their application for the generation of dialkylhydrosilyl anions2021

    • Author(s)
      Takeuchi Takumi、Shishido Ryosuke、Kubota Koji、Ito Hajime
    • Journal Title

      Chemical Science

      Volume: 12 Issue: 35 Pages: 11799-11804

    • DOI

      10.1039/d1sc01440d

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of Chiral α-Amino Tertiary Boronates via the Catalytic Enantioselective Nucleophilic Borylation of Dialkyl Ketimines2021

    • Author(s)
      Kubota Koji、Miura Daiyo、Takeuchi Takumi、Osaki Shun、Ito Hajime
    • Journal Title

      ACS Catalysis

      Volume: 11 Issue: 11 Pages: 6733-6740

    • DOI

      10.1021/acscatal.1c01689

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Introduction of a Luminophore into Generic Polymers via Mechanoradical Coupling with a Prefluorescent Reagent2021

    • Author(s)
      Kubota Koji、Toyoshima Naoki、Miura Daiyo、Jiang Julong、Maeda Satoshi、Jin Mingoo、Ito Hajime
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 60 Issue: 29 Pages: 16003-16008

    • DOI

      10.1002/anie.202105381

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] Exploring Mechanical Force-Induced Organic Synthesis2024

    • Author(s)
      Koji Kubota
    • Organizer
      The 7th ICReDD International Symposium - The Rising Star Program
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Exploring Force-Induced Organic Synthesis2023

    • Author(s)
      Koji Kubota
    • Organizer
      The 3rd Japanese-Sino Symposium on Catalysis for Precision Synthesis
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Advancing the Frontiers of Mechanochemistry2023

    • Author(s)
      Koji Kubota
    • Organizer
      49th IUPAC World Chemistry Congress
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 有機合成化学の”メカノ化”2023

    • Author(s)
      久保田浩司
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 固相メカノ有機合成化学の開拓と展開2023

    • Author(s)
      久保田浩司
    • Organizer
      日本化学会第103春季年会2023
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] マクロとミクロをつなぐメカノ有機合成2023

    • Author(s)
      久保田浩司
    • Organizer
      2022年度第二回有機金属若手研究者の会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Mechano-driven main group organometallic chemistry2022

    • Author(s)
      Koji Kubota
    • Organizer
      The 11th Singapore International Chemistry Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanoredox Catalysis: Force-Induced Charge Transfer Catalysis for Organic Synthesis2022

    • Author(s)
      Koji Kubota
    • Organizer
      International Symposium on Innovative Reactions through Controlling Electrons
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanochemistry-Oriented Reaction Design for Innovative Organic Transformations2022

    • Author(s)
      Koji Kubota
    • Organizer
      錯体化学会 第72回討論会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Solid-state cross-coupling reactions of insoluble aryl halides under polymer-assisted grinding conditions2022

    • Author(s)
      Koji Kubota
    • Organizer
      Faraday Discussion -Mechanochemistry: fundamentals, applications and future
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 有機マグネシウムおよびカルシウム求核剤のメカノケミカル合成と有機合成への応用2022

    • Author(s)
      久保田 浩司・高橋 里奈・Pan Gao・Yunpeng Gao・Angi Hu・Yadong Pang・瀬尾 珠恵・Julong Jiang・前田 理・高谷 光・伊藤 肇
    • Organizer
      第68回有機金属化学討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Mechanoradical Cross-Coupling with Polymers2022

    • Author(s)
      Koji Kubota
    • Organizer
      10th International Conference on Mechanochemistry and Mechanical Alloying
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 空気下における有機マグネシウム試薬のメカノケミカル合成と有機合成への応用2022

    • Author(s)
      久保田 浩司
    • Organizer
      日本化学会第102春季年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ミクロとマクロをつなぐメカノ合成化学2022

    • Author(s)
      久保田 浩司
    • Organizer
      ハイブリッド触媒-分子合成オンデマンドを実現するハイブリッド触媒系の創製- 若手道場オンライン
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] General synthesis of trialkylsilylboranes and their use as silicon nucleophiles2021

    • Author(s)
      Koi Kubota, Ryosuke Shishido, Minami Uesugi, Rikuro Takahashi, Tsuyoshi Miya, Tatsuo Ishiyama, Hajime Ito
    • Organizer
      The 2021 International Chemical Congress of Pacific Basin Societies
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Mechanoredox catalysis for small organic molecule activation2021

    • Author(s)
      Koji Kubota, Yadong Pang, Akira Miura, Hajime Ito
    • Organizer
      The 2021 International Chemical Congress of Pacific Basin Societies
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 固体メカノケミストリー -有機合成の刷新を目指して-2021

    • Author(s)
      久保田 浩司
    • Organizer
      日本プロセス化学会2021 ウィンターシンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 物理的な力を駆動力とする有機合成反応の開発2021

    • Author(s)
      久保田 浩司
    • Organizer
      第七回北海道大学部局横断シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Introduction of a Luminophore Into Generic Polymers via Mechanoradical Coupling Reactions2021

    • Author(s)
      K. Kubota, N. Toyoshima, D. Miura, J. Julong S. Maeda, J. Mingoo, H. Ito
    • Organizer
      第70回高分子討論会
    • Related Report
      2021 Annual Research Report
  • [Presentation] メカノケミカル固体有機合成:進展と展望2021

    • Author(s)
      久保田 浩司
    • Organizer
      第三回有機化学学生ウェビナー
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Mechanochemistry for Molecular Synthesis2021

    • Author(s)
      Koji Kubota
    • Organizer
      Kanazawa University Sakigake Project 2020 Seminar: 4th Ohmiya Lab and Takeda Virtual Symposium
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Tackling Solubulity Issues in Organic Synthesis2021

    • Author(s)
      Koji Kubota
    • Organizer
      Joint Symposium of Engineering Information Science WPI-ICReDD in Hokkaido University
    • Related Report
      2021 Annual Research Report
    • Invited

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Published: 2021-04-28   Modified: 2025-01-30  

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