New Development of Asymmetric Catalytic Reactions Using Chiral Phosphoric Acid

• Project/Area Number: 20H00380
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 33:Organic chemistry and related fields
• Research Institution: Gakushuin University
• Principal Investigator: AKIYAMA TAKAHIKO 学習院大学, 理学部, 教授 (60202553)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥45,500,000 (Direct Cost: ¥35,000,000、Indirect Cost: ¥10,500,000); Fiscal Year 2022: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000); Fiscal Year 2021: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2020: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
• Keywords: 不斉合成 / キラルリン酸 / 触媒 / 光酸化還元触媒 / エナンチオ選択性 / キラリティー / 光反応 / キラルブレンステッド酸 / 光学活性

Outline of Research at the Start

医薬品には，光学活性な化合物が数多く存在し，一方のエナンチオマーは優れた薬理作用を示すが，他方は毒性を示す場合もある。したがって，一方のエナンチオマーのみを合成する手法の開発は，有機化学における重要な課題の一つである。研究代表者のグループでは，キラルブレンステッド酸触媒であるキラルリン酸をすでに開発し，世界中の多くの研究グループで用いられている。本研究では，キラルリン酸触媒反応のさらなる展開を目指して優れた新規不斉触媒反応を開発するとともに，より強力な酸触媒の開発を推進する。将来的には実用化可能な反応の開発を目指す。

Outline of Final Research Achievements

Development of efficient catalyzed enantioselective reactions continues to be an important research area in organic chemistry because of importance in terms of green chemistry. We have developed novel catalyzed reactions using chiral phosphoric acid, and its metal salts. Furthermore, we employed chiral phosphoric acid in the visible light mediated reactions successfully.

Academic Significance and Societal Importance of the Research Achievements

医薬品においては，エナンチオマー間で異なった生理活性を有する場合があり，一方のエナンチオマーを選択的に合成する手法である，伏尾合成反応の開発は重要な研究課題の一つである。その中でも触媒的な不斉合成反応は，少量の不斉源からキラルな化合物を合成することができることから，効率的な手法の一つである。本研究においては，金属を用いない有機触媒を不斉触媒として用いて，新たな触媒反応の開発を行なった。一般に金属錯体は毒性等の問題点があり，安全性の面からも有機触媒を用いた不斉触媒反応の開発は，環境に優しい触媒反応として重要な研究である。

Research Products

• [Journal Article] Enantioselective synthesis of 3-(<i>N</i>-indolyl)quinolines containing axial and central chiralities (2024)
  • Author(s): Yamanomoto Ken、Yamamoto Kota、Yoshida Satoshi、Sato Sota、Akiyama Takahiko
  • Journal Title: Chemical Communications Volume: 60 Issue: 5 Pages: 582-585
  • DOI: 10.1039/d3cc05142k
  • Peer Reviewed
• [Journal Article] Metal- and Additive-Free Synthesis of α-Hydroxyamino Ketones Enabled by Organophotocatalyst (2023)
  • Author(s): Akiyama Takahiko、Yamanomoto Ken、Matsudaira Tadachika
  • Journal Title: Synlett Volume: 34 Issue: 12 Pages: 1391-1394
  • DOI: 10.1055/a-2059-3003
  • Peer Reviewed
• [Journal Article] Enantioselective Synthesis of an All-Carbon Quaternary Stereocenter by Chiral Br?nsted Acid-Catalyzed Friedel?Crafts-Type Reaction between Pyrroles and 3-Indolylmethanols (2023)
  • Author(s): Uchikura Tatsuhiro、S?nchez-Sordo Irene、Yoshimura Tatsuhiko、Makino Yudai、Osakabe Hiroto、Akiyama Takahiko
  • Journal Title: The Journal of Organic Chemistry Volume: 88 Issue: 12 Pages: 7774-7783
  • DOI: 10.1021/acs.joc.2c02633
  • Peer Reviewed
• [Journal Article] 2‐Silylated Dihydroquinazolinone as a Photocatalytic Energy Transfer Enabled Radical Hydrosilylation Reagent (2023)
  • Author(s): Uchikura Tatsuhiro、Nakamura Haruka、Sakai Hinata、Akiyama Takahiko
  • Journal Title: Chemistry- A European Journal Volume: 29 Issue: 45
  • DOI: 10.1002/chem.202301090
  • Peer Reviewed
• [Journal Article] Chiral Phosphoric Acid-Palladium(II) Complex Catalyzed Asymmetric Desymmetrization of Biaryl Compounds by C(sp3)-H Activation (2023)
  • Author(s): Uchikura Tatsuhiro、Kato Sotaro、Makino Yudai、Fujikawa Megumi J.、Yamanaka Masahiro、Akiyama Takahiko
  • Journal Title: Journal of the American Chemical Society Volume: 145 Issue: 29 Pages: 15906-15911
  • DOI: 10.1021/jacs.3c03552
  • Peer Reviewed
• [Journal Article] Visible-light-driven enantioselective intermolecular [2 + 2] photocyclization utilizing bathochromic excitation mediated by a chiral phosphoric acid (2023)
  • Author(s): Uchikura Tatsuhiro、Takahashi Kazuki、Oishi Tatsushi、Akiyama Takahiko
  • Journal Title: Organic &amp; Biomolecular Chemistry Volume: 21 Issue: 46 Pages: 9138-9142
  • DOI: 10.1039/d3ob01425h
  • Peer Reviewed
• [Journal Article] Visible-Light-Driven Enantioselective Radical Addition to Imines Enabled by the Excitation of a Chiral Phosphoric Acid-Imine Complex (2022)
  • Author(s): Uchikura Tatsuhiro、Kamiyama Nanami、Mouri Toshiki、Akiyama Takahiko
  • Journal Title: ACS Catalysis Volume: 12 Issue: 9 Pages: 5209-5216
  • DOI: 10.1021/acscatal.2c00993
  • Peer Reviewed
• [Journal Article] Enantioselective Friedel-Crafts Alkylation Reaction of Pyrroles with <i>N</i>-Unprotected Alkynyl Trifluoromethyl Ketimines (2022)
  • Author(s): Uchikura Tatsuhiro、Aruga Kureha、Suzuki Riku、Akiyama Takahiko
  • Journal Title: Organic Letters Volume: 24 Issue: 25 Pages: 4699-4703
  • DOI: 10.1021/acs.orglett.2c01972
  • Peer Reviewed
• [Journal Article] Dual-Role Halogen-Bonding-Assisted EDA-SET/HAT Photoreaction System with Phenol Catalyst and Aryl Iodide: Visible-Light-Driven Carbon－Carbon Bond Formation (2022)
  • Author(s): Tatsuhiro Uchikura, Kazushi Tsubono, Yurina Hara, Takahiko Akiyama
  • Journal Title: The Journal of Organic Chemistry Volume: 87 Issue: 22 Pages: 15499-15510
  • DOI: 10.1021/acs.joc.2c02032
  • Peer Reviewed
• [Journal Article] ASYMMETRIC ACID ORGANOCATALYSIS (2022)
  • Author(s): Akiyama Takahiko
  • Journal Title: Catalytic Asymmetric Synthesis, Fourth Edition Volume: - Pages: 29-80
  • DOI: 10.1002/9781119736424.ch2
• [Journal Article] Chiral Calcium Phosphate Catalyzed Enantioselective Synthesis of All-Carbon Quaternary Center by Friedel-Crafts Alkylation Reaction of Pyrroles and Trifluoromethylated Nitrostyrenes (2022)
  • Author(s): Akiyama Takahiko、Uchikura Tatsuhiro、Yokohama Sosuke、Murakami Mona
  • Journal Title: Synthesis Volume: 54 Issue: 17 Pages: 3793-3800
  • DOI: 10.1055/s-0040-1719879
  • Peer Reviewed
• [Journal Article] Visible-Light Driven, Metal-Free Hydroalkylation of Alkenes Mediated by Electron Donor-Acceptor Complex Using Benzothiazolines (2021)
  • Author(s): Uchikura Tatsuhiro、Fujii Tatsuya、Moriyama Kaworuko、Akiyama Takahiko
  • Journal Title: Bulletin of the Chemical Society of Japan Volume: 94 Issue: 12 Pages: 2962-2966
  • DOI: 10.1246/bcsj.20210322
  • NAID: 130008144727
  • Peer Reviewed
• [Journal Article] Visible-Light-Driven C-S Bond Formation Based on Electron Donor-Acceptor Excitation and Hydrogen Atom Transfer Combined System (2021)
  • Author(s): Uchikura Tatsuhiro、Hara Yurina、Tsubono Kazushi、Akiyama Takahiko
  • Journal Title: ACS Organic &amp; Inorganic Au Volume: 1 Issue: 1 Pages: 23-28
  • DOI: 10.1021/acsorginorgau.1c00007
  • Peer Reviewed / Open Access
• [Journal Article] Enantioselective Synthesis of 2‐Substituted Indoles Bearing Trifluoromethyl Moiety by the Friedel‐Crafts Alkylation Reaction of 4,7‐Dihydroindole with N ?H Trifluoromethyl Ketimines (2020)
  • Author(s): Uchikura Tatsuhiro、Suzuki Riku、Suda Yusuke、Akiyama Takahiko
  • Journal Title: ChemCatChem Volume: 12 Issue: 19 Pages: 4784-4787
  • DOI: 10.1002/cctc.202000920
  • Peer Reviewed
• [Journal Article] Radical Hydroalkylation and Hydroacylation of Alkenes by the Use of Benzothiazoline under Thermal Conditions (2020)
  • Author(s): Uchikura Tatsuhiro、Toda Mitsuhiro、Mouri Toshiki、Fujii Tatsuya、Moriyama Kaworuko、Ibanez Ignacio、Akiyama Takahiko
  • Journal Title: The Journal of Organic Chemistry Volume: 85 Issue: 19 Pages: 12715-12723
  • DOI: 10.1021/acs.joc.0c01872
  • Peer Reviewed
• [Journal Article] Catalytic trifluoromethylation of iodoarenes by use of 2-trifluoromethylated benzimidazoline as trifluoromethylating reagent (2020)
  • Author(s): Uchikura Tatsuhiro、Kamiyama Nanami、Ishikawa Taisuke、Akiyama Takahiko
  • Journal Title: Beilstein Journal of Organic Chemistry Volume: 16 Pages: 2442-2447
  • DOI: 10.3762/bjoc.16.198
  • Peer Reviewed / Open Access
• [Presentation] Enantioselective Synthesis of Fluorinated Nitrogen-containing Compounds (2024)
  • Author(s): Takahiko Akiyama
  • Organizer: 2nd South Africa Fluorine Symposium
  • Int'l Joint Research / Invited
• [Presentation] Advent of chiral Bronsted acid catalysis, ion pair catalysis: past and future (2024)
  • Author(s): Takahiko Akiyama
  • Organizer: Ion Pairs in the Castle
  • Int'l Joint Research / Invited
• [Presentation] Enantioselective Reactions Catalyzed by Chiral Phosphoric Acid (2023)
  • Author(s): Takahiko Akiyama
  • Organizer: ACS 26th Winter Fluorine Conference
  • Int'l Joint Research / Invited
• [Presentation] キラルリン酸を用いた不斉触媒反応の新展開 (2023)
  • Author(s): 秋山隆彦
  • Organizer: 分子性触媒による高度分子変換技術 第１９４委員会 講演会
  • Invited
• [Presentation] Enantioselective Reactions Catalyzed by Chiral Phosphoric Acid (2023)
  • Author(s): Takahiko Akiyama
  • Organizer: 7th Fluorine Days
  • Int'l Joint Research / Invited
• [Presentation] Chiral Phosphoric Acid-Palladium(II) Complex Catalyzed Asymmetric Desymmetrization of Biaryl Compounds by C(sp3)-H Activation (2023)
  • Author(s): Takahiko Akiyama
  • Organizer: 22nd European Symposium on Organic Chemistry
  • Int'l Joint Research
• [Presentation] Chiral Phosphoric Acid－Palladium(II) Complex Catalyzed Asymmetric Desymmetrization of Biaryl Compounds by C(sp3)－H Activation (2023)
  • Author(s): Takahiko Akiyama
  • Organizer: Catalysis and Fine Chemicals 2023
  • Int'l Joint Research / Invited
• [Presentation] キラルリン酸を用いた触媒反応の新展 (2022)
  • Author(s): 秋山隆彦
  • Organizer: 第32回万有福岡シンポジウム
  • Invited
• [Presentation] Recent Progress in Chiral Phosphoric Acid Catalysis (2022)
  • Author(s): Takahiko Akiyama
  • Organizer: The 5th NYCU Conference on Advanced Organic Synthesis
  • Int'l Joint Research / Invited
• [Presentation] Enantioselective Reactions Catalyzed by Chiral Phosphoric Acid (2022)
  • Author(s): Takahiko Akiyama
  • Organizer: The 15th International Symposium on Organic Reactions 2022
  • Int'l Joint Research / Invited
• [Presentation] キラルリン酸と光触媒の協働作用を利用した不斉触媒反応 (2022)
  • Author(s): 秋山隆彦
  • Organizer: 新学術領域研究「ハイブリッド触媒」第5回公開シンポジウム
• [Presentation] Enantioselective Reactions Catalyzed by Chiral Phosphoric Acid (2022)
  • Author(s): Takahiko Akiyama
  • Organizer: The 15th International Symposium on Organic Reactions 2022 (ISOR-15)
  • Int'l Joint Research / Invited
• [Presentation] Recent Progress in Chiral Phosphoric Acid Catalysis (2022)
  • Author(s): Takahiko Akiyama
  • Organizer: The 5th NYCU Conference on Advanced Organic Synthesis (CAOS-5)
  • Int'l Joint Research / Invited
• [Presentation] キラルリン酸を用いた触媒反応の新展開 (2022)
  • Author(s): 秋山隆彦
  • Organizer: 第32回万有福岡シンポジウム
  • Invited
• [Presentation] Development New Reactions and Technologies Adaptable to Process Chemistry (2021)
  • Author(s): Takahiko Akiyama
  • Organizer: Pacifichem2021
  • Int'l Joint Research
• [Presentation] Enantioselective Reactions Catalyzed by Chiral Phosphoric Acid (2021)
  • Author(s): Takahiko Akiyama
  • Organizer: Pacifichem2021
  • Int'l Joint Research
• [Presentation] キラルリン酸触媒の開発と新展開 (2021)
  • Author(s): 秋山隆彦
  • Organizer: 2021年度前期（春季）有機合成化学講習会
  • Invited
• [Presentation] Enantioselective Reactions Catalyzed by Chiral Phosphoric Acid (2021)
  • Author(s): Takahiko Akiyama
  • Organizer: 2021 Chemical Society National Meeting of Taiwan
  • Int'l Joint Research / Invited
• [Presentation] Enantioselective Reactions Catalyzed by Chiral Phosphoric Acid (2020)
  • Author(s): Takahiko Akiyama
  • Organizer: International Symposium on Organic Reactions 2020 (ISOR 2020)
  • Int'l Joint Research / Invited
• [Book] Asymmetric Acid Organocatalysis, in Catalytic Asymmetric Synthesis, 4th Ed., Edited by Akiyama, T.; Ojima, I.. (2022)
  • Author(s): Takahiko Akiyama
  • Total Pages: 50
  • Publisher: Wiley
• [Book] Organocatalysis in Organofluorine Chemistry, in Frontiers of Organofluorine Chemistry, (2020)
  • Author(s): Takahiko Akiyama
  • Total Pages: 40
  • Publisher: World Scientific
• [Remarks] 学習院大学理学部 秋山研究室
  • URL: https://www.chem.gakushuin.ac.jp/akiyama/
• [Remarks] 学習院大学理学部化学科 秋山研究室
  • URL: https://www.chem.gakushuin.ac.jp/akiyama/