New developments of the asymmetric reactions mediated by chiral phosphoric acid and derivatives

• Project/Area Number: 17H03060
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: Gakushuin University
• Principal Investigator: Akiyama Takahiko 学習院大学, 理学部, 教授 (60202553)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 不斉合成 / 有機分子触媒 / インドール / キラルブレンステッド酸 / 選択的合成 / 還元反応 / 反応開発 / 不斉触媒反応 / 触媒 / BINOL / トリフルオロメチル / キラルリン酸 / 有機合成化学 / トリフルオロメチル基 / 不斉合成反応 / 触媒化学 / 不斉触媒 / 光学活性

Outline of Final Research Achievements

We have developed catalyzed enantioselective reactions by means of chiral phosphoric acid, such as 1) Friedel-Crafts alkylation reactions of pyrrole with N-H CF3 ketimines, 2) Friedel-Crafts alkylation reaction of indole with nitroalkene, 3) dehydrohydrogenation of 2-indolylalcohols, 4) reduction of nitroarenes by use of benzothiazoline and its application to enantioselective synthesis of 2-aryltetrahydroquinoline, 5) [3+2] cycloaddition reaction, and 5) internal redox reaction.

Academic Significance and Societal Importance of the Research Achievements

新たな不斉触媒反応の開発は，新たな医薬品の合成さらには製造段階において用いられる可能性もあり重要な研究課題の一つである。本研究の成果も，遷移金属を用いることなく，有用な化合物の合成につながり，有意義であると考えられる。

Research Products

• [Int'l Joint Research] University of Alicante(スペイン)
• [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] Oxidative Kinetic Resolution of Acyclic Amines Based on Equilibrium Control (2020)
  • Author(s): Saito, K.; Miyashita, H.; Ito, Y.; Yamanaka, M.; Akiyama, T.
  • Journal Title: Org. Lett. Volume: 22 Issue: 8 Pages: 3128-3134
  • DOI: 10.1021/acs.orglett.0c00887
  • Peer Reviewed
• [Journal Article] Enantioselective Dehydroxyhydrogenation of 3-Indolylmethanols by the Combined Use of Benzothiazoline and Chiral Phosphoric Acid: Construction of a Tertiary Carbon Center (2020)
  • Author(s): Osakabe Hiroto、Saito Shota、Miyagawa Masamichi、Suga Takuya、Uchikura Tatsuhiro、Akiyama Takahiko
  • Journal Title: Organic Letters Volume: 22 Issue: 6 Pages: 2225-2229
  • DOI: 10.1021/acs.orglett.0c00430
  • Peer Reviewed
• [Journal Article] Enantioselective Synthesis of 1-Substituted 1,2,3,4-Tetrahydroisoquinolines through 1,3-Dipolar Cycloaddition by a Chiral Phosphoric Acid (2019)
  • Author(s): Jin Yuan、Honma Yasuhiro、Morita Hisashi、Miyagawa Masamichi、Akiyama Takahiko
  • Journal Title: Synlett Volume: 30 Issue: 13 Pages: 1541-1545
  • DOI: 10.1055/s-0039-1690108
  • Peer Reviewed
• [Journal Article] Enantioselective Friedel-Crafts Alkylation Reaction of Indoles with α-Trifluoromethylated β-Nitrostyrenes Catalyzed by Chiral BINOL Metal Phosphate (2019)
  • Author(s): Ibanez, I.; Kaneko, M.; Kamei, Y.; Tsutsumi, R.; Yamanaka, M.; Akiyama, T.
  • Journal Title: ACS Catalysis Volume: 9 Issue: 8 Pages: 6903-6909
  • DOI: 10.1021/acscatal.9b01811
  • Peer Reviewed
• [Journal Article] Enantioselective Friedel-Crafts Alkylation Reaction of Heteroarenes with N‐Unprotected Trifluoromethyl Ketimines by Means of Chiral Phosphoric Acid (2019)
  • Author(s): Miyagawa Masamichi、Yoshida Masaru、Kiyota Yuki、Akiyama Takahiko
  • Journal Title: Chemistry - A European Journal Volume: 25 Issue: 22 Pages: 5677-5681
  • DOI: 10.1002/chem.201901020
  • Peer Reviewed
• [Journal Article] Benzothiazolines as radical transfer reagents: hydroalkylation and hydroacylation of alkenes by radical generation under photoirradiation conditions (2019)
  • Author(s): Uchikura Tatsuhiro、Moriyama Kaworuko、Toda Mitsuhiro、Mouri Toshiki、Ib??ez Ignacio、Akiyama Takahiko
  • Journal Title: Chemical Communications Volume: 55 Issue: 75 Pages: 11171-11174
  • DOI: 10.1039/c9cc05336k
  • Peer Reviewed
• [Journal Article] Chiral Magnesium Bisphosphate Catalyzed Asymmetric Double C(sp3)-H Bond Functionalization Based on Sequential Hydride Shift/Cyclization Process (2018)
  • Author(s): Mori Keiji、Isogai Ryo、Kamei Yuto、Yamanaka Masahiro、Akiyama Takahiko
  • Journal Title: Journal of the American Chemical Society Volume: 140 Issue: 20 Pages: 6203-6207
  • DOI: 10.1021/jacs.8b02761
  • Peer Reviewed
• [Journal Article] Reduction of Nitroarenes to Anilines with a Benzothiazoline: Application to Enantioselective Synthesis of 2-Arylquinoline Derivatives (2018)
  • Author(s): Miyagawa Masamichi、Yamamoto Ryota、Kobayashi Nanako、Akiyama Takahiko
  • Journal Title: Synlett Volume: 30 Issue: 04 Pages: 499-502
  • DOI: 10.1055/s-0037-1611639
  • Peer Reviewed
• [Journal Article] Cooperative Catalysis with Coupled Chiral Induction in 1,3-Dipolar Cycloadditions of Azomethine Ylides (2018)
  • Author(s): Cayuelas Alberto、Larra?aga Olatz、Selva Ver?nica、N?jera Carmen、Akiyama Takahiko、Sansano Jos? M.、de?C?zar Abel、Miranda Jos? I.、Coss?o Fernando P.
  • Journal Title: Chemistry - A European Journal Volume: 24 Issue: 32 Pages: 8092-8097
  • DOI: 10.1002/chem.201801433
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Asymmetric Reduction of Trifluoromethyl Alkynyl Ketimines by Chiral Phosphoric Acid and Benzothiazoline (2018)
  • Author(s): Akiyama Takahiko、Miyagawa Masamichi、Takashima Kensuke
  • Journal Title: Synlett Volume: 29 Issue: 12 Pages: 1607-1610
  • DOI: 10.1055/s-0037-1609755
  • Peer Reviewed
• [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
• [Presentation] Enantioselective Reactions Catalyzed by Chiral Phosphoric Acid (2020)
  • Author(s): Takahiko Akiyama
  • Organizer: Florida Heterocyclic Conference, FLoHet2020
  • Int'l Joint Research / Invited
• [Presentation] Enantioselective Friedel-Crafts Alkylation Reaction of Heteroarenes to Trifluoromethylated N-H Ketimine (2019)
  • Author(s): Takahiko Akiyama
  • Organizer: 19th European Symposium on Fluorine Chemistry
  • Int'l Joint Research
• [Presentation] Enantioselective Friedel-Crafts Alkylation Reaction of Trifluoromethylated N-H Ketimine with Heteroarenes by Means of Chiral Phosphoric Acid (2019)
  • Author(s): Takahiko Akiyama
  • Organizer: 21st European Symposium on Organic Chemistry (ESOC 2019)
  • Int'l Joint Research
• [Presentation] Recent Progress in the Chiral Phosphoric Acid Catalysis (2019)
  • Author(s): Takahiko Akiyama
  • Organizer: TexSyn IV
  • Int'l Joint Research
• [Presentation] Enantioselective Reactions Catalyzed by Chiral Phosphoric Acid (2019)
  • Author(s): Takahiko Akiyama
  • Organizer: The 18th Asian Chemical Congress, IUPAC ChemRAWN Symposium
  • Int'l Joint Research / Invited
• [Presentation] Recent Progress in the Chiral Phosphoric Acid Catalysis (2019)
  • Author(s): Takahiko Akiyama
  • Organizer: International Symposium on Catalysis and Fine Chemicals, (C&FC2019)
  • Int'l Joint Research / Invited
• [Presentation] Enantioselective Synthesis of Fluorinated Compounds by Means of Chiral Phosphoric Acid (2018)
  • Author(s): Takahiko Akiyama
  • Organizer: 6th International Symposium on Organofluorine Compounds in Biomedical, Organic Materials and Agricultural Sciences
  • Int'l Joint Research / Invited
• [Presentation] Enantioselective Friedel-Crafts Alkylation Reaction of Indole with Nitroalkenes by Means of Chiral Phosphoric Acid Metal Salt: Construction of Quaternary Carbon Center (2018)
  • Author(s): Takahiko Akiyama, Mio Kaneko, and Ignacio Ibanez
  • Organizer: XXII International Conference on Organic Synthesis
  • Int'l Joint Research
• [Presentation] Recent Progress in the Chiral Phosphoric Acid Catalysis (2018)
  • Author(s): Takahiko Akiyama
  • Organizer: International Symposium on Catalysis and Fine Chemicals, (C&FC2019)
  • Int'l Joint Research / Invited
• [Presentation] Enantioselective Synthesis of Fluorinated Compounds by Means of Chiral Phosphoric Acid (2018)
  • Author(s): Takahiko Akiyama
  • Organizer: 6th International Symposium on Organofluorine Compounds in Biomedical, Organic Materials and Agricultural Sciences (Nanjing Fluorine Days)
  • Int'l Joint Research / Invited
• [Remarks] 学習院大学理学部化学科 秋山研究室
  • URL: http://www.chem.gakushuin.ac.jp/akiyama/
• [Remarks] 学習院大学理学部化学科 秋山研究室
  • URL: http://www.chem.gakushuin.ac.jp/akiyama/