Development of cyclization reaction based on the internal redox reaction which involves C-H activation reaction

• Project/Area Number: 26288053
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• 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): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 有機合成化学 / 選択的反応 / 炭素ー水素結合活性化 / 環化反応 / 触媒反応 / internal redox reaction / C-H結合官能基化 / ヒドリド移動 / 立体選択性 / 炭素―炭素結合生成反応 / 不斉合成反応 / 炭素-炭素結合生成反応 / 触媒 / 炭素ー炭素結合 / 環状化合物 / 炭素ー炭素結合生成反応

Outline of Final Research Achievements

Development of efficient synthetic method leading to the biologically active compounds represents one of the important task of organic chemistry.
We are interested in the internal redox reaction which involves [1,5]-H shift and subsequent cyclization reaction to form cyclized product. This internal redox reaction does not require external oxidatant because both reduction and oxidation took place in the molecule. We have developed domino internal reaction and enantioselective version of the domino reaction.

Research Products

• [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] Versatile and highly efficient oxidative C(sp3)?H bond functionalization of tetrahydroisoquinoline promoted by bifunctional diethyl azodicarboxylate (DEAD): scope and mechanistic insights (2016)
  • Author(s): Suga Takuya、Iizuka Sunao、Akiyama Takahiko
  • Journal Title: Organic Chemistry Frontiers Volume: 3 Issue: 10 Pages: 1259-1264
  • DOI: 10.1039/c6qo00249h
  • Peer Reviewed
• [Journal Article] Synthesis of 3-Aryl-1-trifluoromethyltetrahydroisoquinolines by Bronsted Acid Catalyzed C(sp3)-H Bond Functionalization (2015)
  • Author(s): Keiji Mori, Nobuaki Umehara andTakahiko Akiyama
  • Journal Title: Adv. Synth. Catal. Volume: 357 Issue: 5 Pages: 901-906
  • DOI: 10.1002/adsc.201400775
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Double C(sp3)-H Bond Functionalization Mediated by Sequential Hydride Shift/Cyclization Process: Diastereoselective Construction of Polyheterocycles (2014)
  • Author(s): Mori, K.; Kurihara, K.; Yabe, S.; Yamanaka, M.; Akiyama, T.
  • Journal Title: J. Am. Chem. Soc. Volume: 136 Issue: 10 Pages: 3744-3747
  • DOI: 10.1021/ja412706d
  • Peer Reviewed
• [Presentation] キラルリン酸金属塩を用いた触媒的不斉二重C(sp3)-H結合官能基化反応の開発 (2017)
  • Author(s): 森啓二・磯貝涼・亀井優斗・山中正浩・秋山隆彦
  • Organizer: 第111回有機合成シンポジウム
• [Presentation] Recent Progress in the Chiral Phosphoric Acid Catalysis (2017)
  • Author(s): Takahiko Akiyama
  • Organizer: The 4th EOC Symosium, Asymmetric Synthesis: the Methods and Applications
  • Int'l Joint Research / Invited
• [Presentation] キラルリン酸金属塩を用いた触媒的不斉二重C(sp3)-H結合官能基化反応の開発 (2017)
  • Author(s): 森啓二・磯貝涼・亀井優斗・山中正浩・秋山隆彦
  • Organizer: 第10回有機触媒シンポジウム
• [Presentation] Asymmetric synthesis of fused piperidine derivatives by the domino internal redox process (2015)
  • Author(s): Ryo Isogai, Keiji Mori, Takahiko Akiyama
  • Organizer: Pacifichem2015
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] アゾジカルボホン酸エステルを酸化剤として用いたテトラヒドロイソキノリン誘導体の 1 
位選択的 C-H 結合置換反応 (2015)
  • Author(s): 飯塚 淳、菅 拓也、秋山隆彦
  • Organizer: 第70回記念有機合成化学協会関東支部新潟(長岡)シンポジウム
  • Place of Presentation: 長岡
  • Year and Date: 2015-11-21
• [Presentation] ドミノ型分子内redox 反応を利用した縮環ピラン骨格の簡便構築法の開発 (2015)
  • Author(s): 梅原 伸彬・森 啓二・秋山 隆彦
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学理工学部
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 分子内redox 反応の逐次利用による縮環ピペリジンの不斉合成 (2015)
  • Author(s): 磯貝 涼・森 啓二・秋山 隆彦
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学理工学部
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] ヒドリド転位型分子内redox系の連続利用による二重C(sp3)-H結合官能基化反応の開発 (2014)
  • Author(s): 森啓二・栗原一樹・矢部真之介・山中正浩・秋山隆彦
  • Organizer: 第105回有機合成シンポジウム
  • Place of Presentation: 東京工業大学大岡山キャンパス
  • Year and Date: 2014-06-10 – 2014-06-11
• [Remarks] 学習院大学理学部秋山研究室
  • URL: http://www.chem.gakushuin.ac.jp/akiyama/
• [Remarks] 秋山研究室ホームページ
  • URL: http://www.chem.gakushuin.ac.jp/akiyama/