含窒素複素芳香環化合物の直接的不斉水素化反応による光学活性環状アミンの効率的合成

• Project/Area Number: 13J01445
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 国内
• Research Field: Organic chemistry
• Research Institution: Osaka University
• Principal Investigator: 飯室 敦弘 大阪大学, 基礎工学研究科, 特別研究員(DC1)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,000,000 (Direct Cost: ¥3,000,000); Fiscal Year 2015: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2014: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2013: ¥1,000,000 (Direct Cost: ¥1,000,000)
• Keywords: 不斉水素化 / イリジウム / ピリジン / イソキノリン

Outline of Annual Research Achievements

3-アミド-2-アリールピリジン塩酸塩の触媒的不斉水素化反応について
光学活性な3-アミノ-2-アリールピペリジン類はニューロキニン1 (NK1) 受容体拮抗薬として有用であるため効率的合成法の開発が強く求められています。光学活性な3-アミノ-2-アリールピペリジン類を得るには2位と3位両方の立体を制御して合成する必要があります。従来の合成法ではピペリジンへの直接的な不斉修飾は困難であり、類縁体の合成にも多くの時間が必要でした。一方でピリジン誘導体から不斉水素化により3-アミノ-2-アリールピペリジンに誘導することができれば、合成工程の大幅な簡略化が期待できます。ピリジン類の不斉水素化反応は本研究員の研究成果を含めて最近いつくか報告されているが、3位に置換基を有する多置換ピリジンを高ジアステレオ選択的かつ高エナンチオ選択的に水素化した例はない。また、芳香族安定化による反応性の低さと生成物であるピペリジンの高い塩基性による触媒の失活という問題がありました。本研究員は3位のアミノ基をトリフルオロアセチル化することにより反応性の向上に成功し、各種配位子検討を行うことにより、3-アミド-2-アリールピリジン塩酸塩の高ジアステレオ選択的かつ高エナンチオ選択的な水素化反応の開発に成功しました。またNK1受容体拮抗薬類縁体の合成に成功しました。本研究成果の一部は学会で発表し、学術論文として投稿中です。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Asymmetric Hydrogenation of 3-Amido-2-arylpyridinium Salts by Triply-chloride-bridged Dinuclear Iridium Complexes Bearing Enantiopure Diphosphine Ligands: Synthesis of Neurokinin-1 Receptor Antagonist Derivatives (2016)
  • Author(s): Atsuhiro Iimuro, Kosuke Higashida, Yusuke Kita, Kazushi Mashima
  • Journal Title: Advanced Synthesis & Catalysis Volume: x Issue: 12 Pages: 1929-1933
  • DOI: 10.1002/adsc.201600203
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enhancing Effects of Salt Formation on Catalytic Activity and Enantioselelectivity for Asymmetric Hydrogenation of Isoquinolinium Salts by Dinuclear Halide-Bridged Iridium Complexes Bearing Chiral Diphosphine Ligands (2015)
  • Author(s): Yusuke Kita, Kenta Yamaji, Kosuke Higashida, Sathaiah Kandula, Atsuhiro Iimuro, Kazushi Mashima*
  • Journal Title: Chemistry A European Journal Volume: 21 Issue: 5 Pages: 1915-1927
  • DOI: 10.1002/chem.201405408
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Asymmetric Hydrogenation of Quinazolium Salts Catalyzed by Halide-Bridged Dinuclear Iridium Complexes Bearing Chiral Diphosphine Ligands (2015)
  • Author(s): Yusuke Kita, Kosuke Higashida, Kenta Yamaji, Atsuhiro Iimuro, Kazushi Mashima*
  • Journal Title: Chemical Communications Volume: 51 Issue: 21 Pages: 4380-4382
  • DOI: 10.1039/c5cc00258c
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Additive Effects on Asymmetric Hydrogenation of N-Heteroaromatics (2014)
  • Author(s): Takuto Nagano, Atsuhiro Iimuro, Kenta Yamaji, Yusuke Kita, Kazushi Mashima
  • Journal Title: Heterocycles Volume: 80 Issue: 1 Pages: 103-127
  • DOI: 10.3987/rev-13-sr(s)2
  • Peer Reviewed
• [Journal Article] Iridium-catalyzed Asymmetric Hydrogenation of Pyridinium Salts for Constructing Multiple Stereogenic Centers on Piperidines (2014)
  • Author(s): Yusuke Kita, Atsuhiro Iimuro, Shoji Hida, Kazushi Mashima
  • Journal Title: Chemistry Letter Volume: 43 Issue: 3 Pages: 284-286
  • DOI: 10.1246/cl.130943
  • NAID: 130004868004
  • Peer Reviewed
• [Presentation] Asymmetric Hydrogenation of 2,3-Disubstituted Pyridinium Salts Catalyzed by Iridium Complexes Bearing Chiral Diphosphine Ligands (2016)
  • Author(s): Atsuhiro Iimuro, Kosuke Higashida, Yusuke Kita, Kazushi Mashima
  • Organizer: 日本化学会 第96春季年会
  • Place of Presentation: 同志社大学 京田辺キャンパス
  • Year and Date: 2016-03-24
• [Presentation] Asymmetric Hydrogenation of Multi-substituted Pyridinium Salts Catalyzed by Chiral Dinuclear Iridium Complexes (2016)
  • Author(s): Atsuhiro Iimuro, Kosuke Higashida, Shoji Hida, Yusuke Kita, Kazushi Mashima
  • Organizer: Biotechnology and Chemistry for Green Growth
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2016-03-09
  • Int'l Joint Research
• [Presentation] Iridium-catalyzed asymmetric hydrogenation of pyridinium salts for constructing multiple stereogenic centers on piperidines (2015)
  • Author(s): Atsuhiro Iimuro, Shoji Hida, Yusuke Kita, Kazushi Mashima
  • Organizer: The International Chemical Congress of Pacific Basin Societies 2015
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Asymmetric Hydrogenation of N-Heteroaromatic Compounds Catalyzed by Iridium Complexes (2015)
  • Author(s): Atsuhiro Iimuro
  • Organizer: 第一回野依フォーラム若手育成塾
  • Place of Presentation: 名古屋大学野依記念館
  • Year and Date: 2015-07-16
• [Presentation] Iridium-Catalyzed Asymmetric Hydrogenation of Multi-substituted Pyridinium Salts (2015)
  • Author(s): Atsuhiro Iimuro, Shoji Hida, Yusuke Kita, Kazushi Mashima
  • Organizer: 18th International Conference on Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS18)
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2015-06-28
  • Int'l Joint Research
• [Presentation] Asymmetric Hydrogenation of Multi-Substituted Pyridinium Salts Catalyzed by Iridium(III) Complexes (2014)
  • Author(s): ◯Atsuhiro Iimuro, Shoji Hida, Yusuke Kita, Kazushi Mashima*
  • Organizer: ETH Zurich-Osaka Univ. Joint Symposium
  • Place of Presentation: 大阪大学、大阪
  • Year and Date: 2014-10-10
• [Presentation] Iridium-Catalyzed Asymmetric Hydrogenation of Multi-substituted Pyridinium Salts (2014)
  • Author(s): ◯Atsuhiro Iimuro, Shoji Hida, Yusuke Kita, Kazushi Mashima*
  • Organizer: 19th International Symposium on Homogeneous Catalysis (ISHC XIX)
  • Place of Presentation: Ottawa, Canada
  • Year and Date: 2014-06-08
• [Presentation] Salt Formation Strategy for Asymmetric Hydrogenation of N-Heteroaromatic Compounds (2014)
  • Author(s): Atsuhiro limuro, Kenta Yamaji, Shoji Hida, Yusuke Kita, Kazushi Mashima
  • Organizer: 7^<th> CaRLa Winter School 2014 Heidelberg
  • Place of Presentation: Deutsch Amerikanisches Institut (Germany)
  • Year and Date: 2014-02-24
  • Invited
• [Presentation] Iridium-catalyzed Asymmetric Hydrogenation of Pyridium Salts (2013)
  • Author(s): Atsuhiro Iimuro, Shoji Hida, Yusuke Kita, Kazushi Mashima
  • Organizer: Intemational Rcsearch Training Group "Selectivity in Chemo-and Biocatalysis" Aachen-Osaka Joint Symposium
  • Place of Presentation: RWTH Aachen (Germany)
  • Year and Date: 2013-12-02
• [Presentation] Construction of Multiple Stereogenic Centers on Piperidines by Iridium-catalyzed Asymmetric Hydrogenation of Pyridinium Salts (2013)
  • Author(s): 飯室敦弘・樋田翔士・喜多祐介・真島和志
  • Organizer: 第60回有機金属化学討論会
  • Place of Presentation: 学習院大学(東京都)
  • Year and Date: 2013-09-12
• [Presentation] Synthesis of Optically Active 1,2,3,4-Tetarahydroisoquinolines by Iridium-catalyzed Asymmetric Hydrogenation of lsoquinlinium Salts (2013)
  • Author(s): Atsuhiro Iimuro, Kenta Yamaji, Sathaiah Kandula, Takuto Nagano、Yusuke Kita, Kazushi Mashima
  • Organizer: 17th IUPAC Intemational Symposium on Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS 17)
  • Place of Presentation: Colorado State University (US)
  • Year and Date: 2013-07-29
• [Remarks] 真島研究室 Web ページ：業績リスト
  • URL: http://www.organomet.chem.es.osaka-u.ac.jp/
• [Remarks] (真島研究室Webページ : 業績リスト)
  • URL: http://www.organomet.chem.es.osaka-u.ac.jp/