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Development of Strong Bronsted Base Hybrid Catalyst Systems for Stereoselective Carbon-Carbon Bond Forming Reactions

Planned Research

Project AreaHybrid Catalysis for Enabling Molecular Synthesis on Demand
Project/Area Number 17H06448
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Science and Engineering
Research InstitutionThe University of Tokyo

Principal Investigator

Yamashita Yasuhiro  東京大学, 大学院理学系研究科(理学部), 准教授 (90334341)

Project Period (FY) 2017-06-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥54,990,000 (Direct Cost: ¥42,300,000、Indirect Cost: ¥12,690,000)
Fiscal Year 2021: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2020: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2019: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2018: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2017: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Keywords強塩基 / 触媒 / 不斉合成 / ハイブリッド / 固相塩基 / ハイブリッド触媒 / ハイブリッド触媒系
Outline of Final Research Achievements

We have developed a hybrid catalyst system consisting of a strong base catalyst and a metal or organo catalyst, and applied for catalytic stereoselective reactions using a raw material that is easily available but has poor reactivity. Catalytic asymmetric Mannich reactions using a propionamide, which is a weakly acidic compound, and catalytic asymmetric addition reactions of alkylarenes, such as toluene, and propylene with imines were realized by using chiral strong base hybrid catalyst systems. By constructing a hybrid catalyst system of a base catalyst and an organo photocatalyst, we developed catalytic reactions between styrenes and malonic acid esters, which do not react using the base catalyst alone. We have also developed K/γ-Al2O3 as a strong solid base catalyst and realized catalytic 1,4-addition reactions of a propionamide in a flow reaction system.

Academic Significance and Societal Importance of the Research Achievements

構造が単純で入手容易な原料を用いて、医薬品等の高付加価値な有機分子を短工程で合成するための方法論の開発は、合成過程で生じる廃棄物の低減化や省エネルギー化につながるため、社会的意義の大きい環境調和型有機合成を実現する上で最も期待されている研究の一つである。本研究では、医薬品合成中間体として有用な化合物を、安価で入手容易であるが反応性に乏しい原料から直接触媒反応により立体選択的に合成することに成功した。これらの触媒反応は、従来の手法では実現が困難であり、その実現は学術的意義が大きいと言える。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (52 results)

All 2022 2021 2020 2019 2018

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 1 results) Presentation (37 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Development of chiral potassium strong Bronsted base catalysts for enantioselective carbon-carbon bond-forming reactions2022

    • Author(s)
      Yasuhiro Yamashita
    • Journal Title

      Chem. Commun.

      Volume: 58 Issue: 8 Pages: 1078-1088

    • DOI

      10.1039/d1cc06328f

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bronsted base-catalyzed imino-ene-type allylation reactions of simple alkenes as unactivated allyl compounds2022

    • Author(s)
      Yasuhiro Yamashita, Io Sato, Ryota Fukuyama, Shu Kobayashi
    • Journal Title

      Chem. Commun.

      Volume: 58 Issue: 17 Pages: 2866-2869

    • DOI

      10.1039/d1cc06983g

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthetic Organic “Aquachemistry” that Relies on Neither Cosolvents nor Surfactants2021

    • Author(s)
      Kitanosono Taku, Kobayashi Shu
    • Journal Title

      ACS Cent. Sci.

      Volume: - Issue: 15 Pages: 5598-5605

    • DOI

      10.1021/jacs.0c13317

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] alpha-Alkylation of Ketones with Alkenes Enabled by Photoinduced Activation of Silyl Enol Ethers in the Presence of a Small Amount of Water2021

    • Author(s)
      Tsubasa Hirata, Yoshihiro Ogasawara, Yasuhiro Yamashita, Shu Kobayashi
    • Journal Title

      Org. Lett.

      Volume: 23 Issue: 15 Pages: 5693-5697

    • DOI

      10.1021/acs.orglett.1c01824

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enantioselective hydrophosphonylation of N-Boc imines using chiral guanidine-thiourea catalysts2021

    • Author(s)
      Louis Chassillan, Yasuhiro Yamashita, Woo-Jin Yoo, Martial Toffano, Regis Guillot, Shu Kobayashi, Giang Vo-Thanh
    • Journal Title

      Org. Biomol. Chem.

      Volume: 19 Issue: 48 Pages: 10560-10564

    • DOI

      10.1039/d1ob01953h

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New Dimensions of Bronsted Base Catalyzed Carbon-Carbon Bond-Forming Reactions2021

    • Author(s)
      Yasuhiro Yamashita, Shu Kobayashi
    • Journal Title

      Synlett

      Volume: 32 Issue: 01 Pages: 14-22

    • DOI

      10.1055/s-0040-1707202

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly Enantioselective Immobilized Prolinamide-catalyzed Aldol Reactions in Continuous-flow Systems: Effect of Water on the Catalyst Lifetime and Application in the Synthesis of a Chiral Fenpentadiol Analogue2021

    • Author(s)
      Caizhen, Yue, Yasuhiro Yamashita, Shu Kobayashi
    • Journal Title

      Green Chemistry

      Volume: 23 Issue: 5 Pages: 1989-1994

    • DOI

      10.1039/d0gc04202a

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Asymmetric C(sp3)-H Functionalization of Unactivated Alkylarenes such as Toluene Enabled by Chiral Bronsted Base Catalysts2021

    • Author(s)
      Tsubasa Hirata, Io Sato, Yasuhiro Yamashita, Shu Kobayashi
    • Journal Title

      Communications Chemistry

      Volume: 4 Issue: 1 Pages: 36-36

    • DOI

      10.1038/s42004-021-00459-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Bronsted Base-Photocatalyst Hybrid Systems for Highly Efficient C-C Bond Formation Reactions of Malonates with Styrenes2020

    • Author(s)
      Bas Sebastian, Yasuhiro Yamashita, Shu Kobayashi
    • Journal Title

      ACS Catalysis

      Volume: 10 Issue: 18 Pages: 10546-10550

    • DOI

      10.1021/acscatal.0c02716

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Solid Superbase-Catalyzed Stereoselective 1,4-Addition Reactions of Simple Amides in Batch and Continuous-Flow System2019

    • Author(s)
      Parijat Borah, Yasuhiro Yamashita, Shu Kobayashi
    • Journal Title

      Adv. Synth. Catal.

      Volume: 361 Issue: 16 Pages: 3807-3812

    • DOI

      10.1002/adsc.201900364

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alkylpotassium-Catalyzed Benzylic C-H Alkylation of Alkylarenes with Alkenes2019

    • Author(s)
      Io Sato, Yasuhiro Yamashita, Shu Kobayashi
    • Journal Title

      Synthesis

      Volume: 51 Issue: 01 Pages: 240-250

    • DOI

      10.1055/s-0037-1610378

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catalytic AlkylationReactions of Weakly Acidic Carbonyl and Related Compounds using alkenes as electrophiles2018

    • Author(s)
      Yasuhiro Yamashita, Ryo Igarashi, Hirotsugu Suzuki, Shu Kobayashi
    • Journal Title

      Organic Biomolecular Chemistry

      Volume: 16 Issue: 33 Pages: 5969-5972

    • DOI

      10.1039/c8ob00941d

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catalytic Addition Reactions of Alkylazaarenes to Vinylsilanes2018

    • Author(s)
      Yasuhiro Yamashita, Kodai Minami, Shu Kobayashi
    • Journal Title

      Chemistry Letters

      Volume: 47 Issue: 5 Pages: 690-692

    • DOI

      10.1246/cl.180132

    • NAID

      130006732212

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catalytic Direct-type Addition Reactions of Alkylareens with Imines and Alkenes2018

    • Author(s)
      Yasuhiro Yamashita, Hirotsugu Suzuki, Io Sato, Tsubasa Hirata, Shu Kobayashi
    • Journal Title

      Angewandte Chemie International Edition

      Volume: in press Issue: 23 Pages: 6896-6900

    • DOI

      10.1002/anie.201711291

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catalytic Carbon-Carbon Bond-Forming Reactions of Weakly Acidic Carbon Pronucleophiles Using Strong Bronsted Bases as Catalysts2018

    • Author(s)
      Yasuhiro Yamashita, Shu Kobayashi
    • Journal Title

      Chemistry - A European Journal

      Volume: 24 Issue: 1 Pages: 10-17

    • DOI

      10.1002/chem.201703404

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 高分子固定化キラル強塩基触媒系の最適化2022

    • Author(s)
      木村友哉、山下恭弘、小林修
    • Organizer
      日本化学会第102春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Development of Chiral Strong Bronsted Base Catalyst Systems for Asymmetric Addition Reactions of Various Alkylarenes with Imines2022

    • Author(s)
      Damir Medunjanin, Tsubasa Hirata, Yasuhiro Yamashita, Shu Kobayashi
    • Organizer
      日本化学会第102春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Development of Catalytic Enantioselective Mannich Reactions of Esters and Effective Transformations of the Mannich Adducts toward Asymmetric Synthesis of β-Lactams2022

    • Author(s)
      Seiya Fushimi, Tomoya Kimura, Yasuhiro Yamashita, Shu Kobayashi
    • Organizer
      日本化学会第102春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ケテンシリルアセタールの酸化的活性化によるアルケンを用いたエステルのα-アルキル化反応の開発2022

    • Author(s)
      小笠原由紘、平田翼、山下恭弘、小林修
    • Organizer
      日本化学会第102春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Development of Addition Reactions of Ketones with Alkenes through Photo-Induced Activation of Their Enolates2022

    • Author(s)
      Tsubasa Hirata, Yoshihiro Ogasawara, Yasuhiro Yamashita, Shu Kobayashi
    • Organizer
      日本化学会第102春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 剛直な骨格をもつキラルグアニジンーチオウレア触媒を用いるイミンへのヒドロホスホニル化反応の開発2022

    • Author(s)
      Yasuhiro Yamashita, Louis Chassillan, Woo-Jin Yoo, Martial Toffano, Regis Guillot, Shu Kobayashi, Giang Vo-Thanh
    • Organizer
      日本化学会第102春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Development of Chiral Potassium Strong Base Catalysts for Enantioselective Carbon-Carbon Bond Forming Reactions2021

    • Author(s)
      Yasuhiro Yamashita, Shu Kobayashi
    • Organizer
      Pacifichem 2021
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Development of Addition Reactions of Alkylazaarenes with Imines Using Strong Base Catalyst Systems2021

    • Author(s)
      Hyemin Cho, Yasuhiro Yamashita, Shu Kobayashi
    • Organizer
      日本化学会第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] キラル強塩基触媒による酢酸エステルの不斉Mannich反応の開発2021

    • Author(s)
      伏見星哉、木村友哉、山下恭弘、小林修
    • Organizer
      日本化学会第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高分子固定化キラル強塩基触媒系を用いる 不斉 Mannich 反応の開発2021

    • Author(s)
      木村友哉、野口愛加、山下恭弘、小林修
    • Organizer
      日本化学会第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エノールシリルエーテルを活用する アルケンによるケトンα位のアルキル化反応の開発2021

    • Author(s)
      平田翼、小笠原由紘、山下恭弘、小林修
    • Organizer
      日本化学会第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 光酸化還元触媒を用いた エノールシリルエーテルとアルケンとの反応の展開2021

    • Author(s)
      小笠原由紘、平田翼、山下恭弘、小林修
    • Organizer
      日本化学会第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高分子固定化プロリンアミドを用いた トリフルオロアセトフェノン類とケトンとの 連続フロー不斉アルドール反応の開発2021

    • Author(s)
      山下恭弘、Caizhen Yue、小林 修
    • Organizer
      日本化学会第101春季年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Immobilization of Chiral Secondary Amine Catalysts and Its Application in Continuous-Flow Reactions2020

    • Author(s)
      Yue, C.; Yamashita, Y.; Kobayashi, S.
    • Organizer
      日本化学会第100春季年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of Polymer-Immobilized Chiral Macrocyclic Crown Ethers and Application to Strong Base-Catalyzed Asymmetric 1,4-Addition Reactions2020

    • Author(s)
      Ko, J.-H.; Hirata, T.; Yamashita, Y.; Kobayashi, S.
    • Organizer
      日本化学会第100春季年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of Asymmetric Addition Reactions of Alklyazaarenes with Imines Using Chiral Metal Salt-Strong Base Hybrid Catalyst Systems2020

    • Author(s)
      Cho, H.; Noguchi, A.; Yamashita, Y.; Kobayashi, S.
    • Organizer
      日本化学会第100春季年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] キラル金属塩・強塩基ハイブリッド触媒系を用いる不斉Mannich型反応2020

    • Author(s)
      野口愛加、山下恭弘、小林修
    • Organizer
      日本化学会第100春季年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of Catalytic Asymmetric Addition Reactions of Unactivated Alkylarenes with Imines Enabled by Chiral Potassium Bases2020

    • Author(s)
      Hirata, T.; Sato, I.; Yamashita, Y.; Kobayashi, S.
    • Organizer
      日本化学会第100春季年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] キラルアルカリ金属塩を不斉触媒源として用いる低酸性化合物の不斉Mannich型反応の開発2020

    • Author(s)
      山下恭弘、小林修
    • Organizer
      日本化学会第100春季年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of Catalytic Carbon-Carbon Bond Forming Reactions of Unactivated Alkylarenes Using Alkaline Metal Catalysts2019

    • Author(s)
      Yamashita, Y.; Kobayashi, S.
    • Organizer
      OMCOS 20
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of Catalytic Carbon-Carbon Bond Forming Reactions of Weakly Acidic Compounds Using Alkaline Metal Base Catalysts2019

    • Author(s)
      Yamashita, Y.
    • Organizer
      The 1st International Symposium on Hybrid Catalysis for Enabling Molecular Synthesis in Demand "Development of Catalytic Carbon-Carbon Bond Forming Reactions of Weakly Acidic Compounds U
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 強塩基触媒によるアルキルアレーンのイミンに対する高立体選択的付加反応の開発2019

    • Author(s)
      平田翼、佐藤維央、山下恭弘、小林修
    • Organizer
      第116回有機合成シンポジウム2019年【秋】
    • Related Report
      2019 Annual Research Report
  • [Presentation] キラルアルカリ金属強塩基触媒の開発および低酸性化合物の触媒的不斉付加反応への展開2019

    • Author(s)
      山下恭弘、小林修
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 強塩基触媒を用いるアルキルアレーンのβ-置換ビニルシランに対する付加反応の開発2019

    • Author(s)
      佐藤維央、山下恭弘、小林修
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 単純アルケンを原料として用いる直接的触媒的炭素-炭素結合形成反応の開発2019

    • Author(s)
      福山遼大、佐藤維央、山下恭弘、小林修
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] キラル強塩基触媒によるアルキルアレーンのイミンに対する不斉付加反応の開発2019

    • Author(s)
      平田翼、佐藤維央、山下恭弘、小林修
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 単純アミドを用いる直接的触媒的不斉Mannich型反応の開発2019

    • Author(s)
      野口愛加、山下恭弘、小林修
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 単純エステルを用いる直接的触媒的不斉Mannich型反応の開発2019

    • Author(s)
      伏見星哉、山下恭弘、小林修
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of Strong Base-Photocatalyst Hybrid Systems for Catalytic Carbon-carbon Bond Forming Reactions2019

    • Author(s)
      Sebastian Bas、山下恭弘、小林修
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 典型金属触媒を用いる低酸性炭素―水素結合の直接的変換反応の開発2018

    • Author(s)
      山下恭弘
    • Organizer
      有機合成化学ミニシンポジウム千葉
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] New Dimension of Bronsted Base-catalyzed Addition Reactions of Weakly Acidic Carbon Pronucleophiles2018

    • Author(s)
      Yasuhiro Yamashita, Shu Kobayashi
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] プロピレンを用いた イミンの直接的触媒的アリル化反応の開発2018

    • Author(s)
      福山遼大、佐藤維央、山下恭弘、小林 修
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 強塩基触媒による アルキルアレーンのイミンに対する 立体選択的付加反応の開発2018

    • Author(s)
      平田翼、佐藤維央、鈴木弘嗣、山下恭弘、小林修
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 強塩基触媒を用いる低酸性化合物の炭素-炭素/炭素-窒素二重結合への付加反応の開発2018

    • Author(s)
      五十嵐諒、鈴木弘嗣、山下恭弘、小林修
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Strong Base-catalyzed C-C Bond Formation of Alkylarenes with Olefins2018

    • Author(s)
      Io Sato, Yasuhiro Yamashita, Shu Kobayashi
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Stereoselective Direct-Type 1,4-Addition Reactions of Simple Amides and Esters Using Solid Superbase2018

    • Author(s)
      Parijat Borah, Yasuhiro Yamashita, Shu Kobayashi
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Bronsted塩基触媒系を活用する効率的炭素ー炭素結合生成反応の開発2018

    • Author(s)
      山下恭弘
    • Organizer
      新学術領域研究「ハイブリッド触媒」 第一回公開シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2017-07-04   Modified: 2023-01-30  

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