Regioselective Trifluoromethylation via Activation of PyridinesRegioselective Trifluoromethylation via Activation of Pyridines

• Project/Area Number: 18K14222
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: Yamaguchi University
• Principal Investigator: Kawamoto Takuji 山口大学, 大学院創成科学研究科, 助教 (70756139)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ラジカル / トリフルオロメチル / ピリジン / ピリジニウム / イミン / ピリドン / イオン / ペルフルオアルキル

Outline of Final Research Achievements

We developed The one-pot triflation/radical trifluoromethylation/triflation of imines leading to CF3-substituted vinyl trifluoromethanesulfonyl amides. The reaction proceeds via the radical trifluoromethylation of vinyl trifluoromethanesulfonyl amides as the key step. This reaction is suitable for a variety of imines having halogen atoms, electron-donating groups, and electron-withdrawing groups in moderate to good yields. Vinyl trifluoromethanesulfonyl amides can act as bifunctional reagents, whereby they serve as the trifluoromethyl radical source and radical acceptor.

Academic Significance and Societal Importance of the Research Achievements

トリフルオロメチル基を有機分子に導入すると化合物の代謝安定性，脂溶性，生物学的利用能が向上する。そのため，これまでにトリフルオロ基を有する様々な 医薬品が開発されている。本研究では，ビニルトリフルオロメタンスルホニルアミドを用いる新しいトリフルオロメチル化反応を開発した。得られた化合物は医農薬への応用が期待できる。

Research Products

• [Journal Article] Redox‐Neutral Tetrafluoroethylation of Aryl Alkynes with 1,1,2,2‐Tetrafluoroethane Sulfonic Acid Leading to α‐Tetrafluoroethylated Acetophenones (2021)
  • Author(s): Kawamoto Takuji、Noguchi Kohki、Takata Ryotaro、Sasaki Rio、Matsubara Hiroshi、Kamimura Akio
  • Journal Title: Chemistry A European Journal Volume: - Issue: 37 Pages: 9529-9534
  • DOI: 10.1002/chem.202100137
  • Peer Reviewed
• [Journal Article] Inverse Hydroboration of Imines with NHC-Boranes Is Promoted by Diphenyl Disulfide and Visible Light (2021)
  • Author(s): Kawamoto Takuji、Morioka Tsubasa、Noguchi Kohki、Curran Dennis P.、Kamimura Akio
  • Journal Title: Organic Letters Volume: 23 Issue: 5 Pages: 1825-1828
  • DOI: 10.1021/acs.orglett.1c00230
  • Peer Reviewed
• [Journal Article] Synthesis of 1-(1-Arylvinyl)pyridin-2(1H)-ones from Ketones and 2-Fluoropyridine (2021)
  • Author(s): Kawamoto Takuji、Ikeda Shunya、Kamimura Akio
  • Journal Title: ChemRxiv Volume: -
  • DOI: 10.26434/chemrxiv.14167283.v1
  • Open Access
• [Journal Article] Hydrodecyanation of Secondary Alkyl Nitriles and Malononitriles to Alkanes using DiMeImd-BH3 (2020)
  • Author(s): Kawamoto Takuji、Oritani Kyohei、Kawabata Atsushi、Morioka Tsubasa、Matsubara Hiroshi、Kamimura Akio
  • Journal Title: The Journal of Organic Chemistry Volume: 85 Issue: 9 Pages: 6137-6142
  • DOI: 10.1021/acs.joc.0c00105
  • Peer Reviewed
• [Journal Article] The regioselective trifluoromethylation of 1,3-bis(vinyl triflates) in the absence of external trifluoromethyl sources (2019)
  • Author(s): Kawamoto Takuji、Sasaki Rio、Kamimura Akio、Matsubara Hiroshi
  • Journal Title: Journal of Fluorine Chemistry Volume: 221 Pages: 66-69
  • DOI: 10.1016/j.jfluchem.2019.04.002
  • Peer Reviewed
• [Presentation] トリフルオロメタンスルホン酸無水物を用いるトリフルオロメチル化反応 (2020)
  • Author(s): 山崎哲志，三井準也，川本拓治，上村明男
  • Organizer: 日本化学会第100春季年会
• [Presentation] アセトフェノン類を用いたN-ビニル置換ピリドンの合成 (2020)
  • Author(s): 池田瞬也，川本拓治，上村明男
  • Organizer: 日本化学会第100春季年会
• [Presentation] テトラフルオロエタンスルホン酸を用いるラジカル反応の開発 (2020)
  • Author(s): 野口光貴，川本拓治，上村明男
  • Organizer: 日本化学会第100春季年会
• [Presentation] β-トリフルオロメチルベンジルアミンの新規合成法の開発 (2020)
  • Author(s): 井川恵祐，青山恒平，川本拓治，上村明男
  • Organizer: 日本化学会第100春季年会