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2013 Fiscal Year Annual Research Report

二重活性化型有機分子触媒を用いるキラル多官能性化合物の合成と応用

Publicly Offered Research

Project AreaAdvanced Molecular Transformations by Organocatalysts
Project/Area Number 24105518
Research InstitutionOsaka University

Principal Investigator

滝澤 忍  大阪大学, 産業科学研究所, 准教授 (50324851)

Project Period (FY) 2012-04-01 – 2014-03-31
Keywords有機分子触媒 / 酸 / 塩基 / ドミノ / エナンチオ選択的 / 位置選択的 / 環化付加 / 複素環
Research Abstract

本研究の目的は、基質の活性化に金属を必要としない二重活性化能を有する高活性な酸-塩基型有機分子不斉触媒を創製し、開発した触媒を用いて森田-Baylis-Hillman(MBH)反応を基軸とする不斉連続的炭素-炭素結合生成反応(不斉ドミノ反応)を検討することにある。今年度は、医薬品原料や生物活性天然物の母格となる多置換・多官能性キラル化合物群の安全で効率的な合成法の確立を念頭に、含窒素環化合物であるアゼチジンやテトラヒドロピリジン類に注目した。これら複素環化合物は、薬理活性物質の母核として、また金属配位子としても興味深く、これまでに数多くの研究が報告されている。しかしながら、その光学活性体合成には多工程を必要とした。そこで入手容易なアレノエートを求核種とするケチミンとの形式的[n+2]不斉環化付加反応により、キラル四置換炭素を有する多置換アゼチジンおよびテトラヒドロピリジン類の簡便合成を試みた。非環状ケチミンとアレノエートを基質に反応条件を精査したところ、酸-塩基型不斉有機分子触媒β-isocupreidine(β-ICD)存在下、MS 3Aを添加し、THF:1,4-ジオキサン(1:2)の混合溶媒中、-5 ℃下で反応を行うと、高収率でアゼチジンが得られることを見出した。また、環状ケチミンとα位にメチル基を有するアレノエートとの反応において、モノアリールホスフィン触媒SITCPを用いると形式的[4+2]環化付加反応が高エナンチオ選択的に進行することが判明した。各種NMRデータ、単結晶X線構造解析、および類似光学活性体との旋光度の比較等から、形式的[2+2]環化付加反応ではアゼチジンがE選択的にR体で得られ、形式的[4+2]環化付加反応ではテトラヒドロピリジンが高位置選択的にR体で得られていることが分かった。本反応から得られる環化体は、β-アミノ酸誘導体であり、医薬品中間体等のキラルビルディングブロックとしての応用が期待される。

Current Status of Research Progress
Reason

25年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

25年度が最終年度であるため、記入しない。

  • Research Products

    (19 results)

All 2014 2013

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (13 results) (of which Invited: 1 results)

  • [Journal Article] Enantioselective Organocatalyzed Formal [4+2] Cycloaddition of Ketimines with Allenoates: Easy Access to a Tetrahydropyridine Framework with a Chiral Tetrasubstituted Carbon Stereogenic Center2014

    • Author(s)
      Takizawa, S.; Arteaga, F. A.; Yoshida, Y.; Suzuki, M.; Sasai, H.
    • Journal Title

      Asian J. Org. Chem.

      Volume: 3 Pages: 412-415

    • DOI

      10.1002/ajoc.201300244

    • Peer Reviewed
  • [Journal Article] P-Chirogenic organocatalysts: Application to the aza-Morita-Baylis-Hillman (aza-MBH) reaction of ketimines2013

    • Author(s)
      Takizawa, S.; Remond, E.; Arteaga, F. A.; Yoshida, Y.; Sridharan, V.; Bayardon, J.; Juge, S.; Sasai, H.
    • Journal Title

      Chem. Commun.

      Volume: 49 Pages: 8392-8394

    • DOI

      10.1039/C3CC44549F

    • Peer Reviewed
  • [Journal Article] Organocatalyzed formal [2+2] cycloaddition of ketimines with allenoates: Facile access to azetidines with a chiral tetrasubstituted carbon stereogenic center2013

    • Author(s)
      Takizawa, S.; Arteaga, F. A.; Yoshida, Y.; Suzuki, M.; Sasai, H.
    • Journal Title

      Org. Lett.

      Volume: 15 Pages: 4142-4145

    • DOI

      10.1021/ol401817q

    • Peer Reviewed
  • [Journal Article] Chiral bifunctional organocatalysts bearing a 1,3-propanediamine unit for the aza-MBH reaction2013

    • Author(s)
      Hirata, S.; Tanaka, K.; Matsui, K.; Arteaga, F. A.; Yoshida, Y.; Takizawa, S.; Sasai, H.
    • Journal Title

      Tetrahedron: Asymmetry

      Volume: 24 Pages: 1189-1192

    • DOI

      10.1016/j.tetasy.2013.08.005

    • Peer Reviewed
  • [Journal Article] o-(Hydroxyalkyl)phenyl P-chirogenic phosphines as functional chiral Lewis bases2013

    • Author(s)
      Remond, E.; Bayardon, J.; Takizawa, S.; Rousselin, Y.; Sasai, H.; Juge, S.
    • Journal Title

      Org. Lett.

      Volume: 15 Pages: 1870-1873

    • DOI

      10.1021/ol400515e

    • Peer Reviewed
  • [Journal Article] Facile synthesis of α-methylidene-γ-butyrolactones: Intramolecular Rauhut-Currier reaction promoted by chiral acid-base organocatalysts2013

    • Author(s)
      Takizawa, S.; Nguyen, T. M.-N.; Grossmann, A.; Suzuki, M.; Enders, D.; Sasai, H.
    • Journal Title

      Tetrahedron

      Volume: 69 Pages: 1202-1209

    • DOI

      10.1016/j.tet.2012.11.046

    • Peer Reviewed
  • [Presentation] Development of Chiral Catalyst Based on Functionalization of 1,2,3-Triazoles2014

    • Author(s)
      Yoshida, Y.; Takizawa, S.; Sasai, H.
    • Organizer
      The 17th SANKEN International Symposium
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      20140121-20140122
  • [Presentation] Enantioselective Organocatalyzed Formal [n+2] Cycloaddition Using Ketimines and Allenoates2014

    • Author(s)
      Arteaga, F. A.; Takizawa, S.; Yoshida, Y.; Suzuki, M.; Sasai, H.
    • Organizer
      The 17th SANKEN International Symposium
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      20140121-20140122
  • [Presentation] Chiral Trisimidazole-Catalyzed Friedel-Crafts (FC)-type Reaction2014

    • Author(s)
      Hirata, S.; Takizawa, S.; Murai, K.; Fujioka, H.; Sasai, H.
    • Organizer
      The 17th SANKEN International Symposium
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      20140121-20140122
  • [Presentation] Enantioselective Synthesis of Alfa-Methylidene-Ganma-Butyrolactones: Intramolecular Rauhut-Currier Reaction Promoted by Acid/Base Organocatalysts2013

    • Author(s)
      Nguyen, T. M.-N.; Grossmann, A.; Takizawa, S.; Suzuki, M.; Enders, D.; Sasai, H.
    • Organizer
      First Osaka University-EPFL International Symposium
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      20131202-20131204
  • [Presentation] Enantioselective Organocatalyzed Formal [n+2] Cycloaddition of Ketimines2013

    • Author(s)
      Arteaga, F. A.; Takizawa, S.; Yoshida, Y.; Suzuki, M.; Sasai, H.
    • Organizer
      First Osaka University-EPFL International Symposium
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      20131202-20131204
  • [Presentation] Enantioselective Organocatalyzed Formal [n+2] Cycloaddition of Ketimines with Allenoates2013

    • Author(s)
      Arteaga, F. A.; Takizawa, S.; Yoshida, Y.; Suzuki, M.; Sasai, H.
    • Organizer
      The 8th International Symposium on Integrated Synthesis
    • Place of Presentation
      Nara, Japan
    • Year and Date
      20131129-20131201
  • [Presentation] Enantioselective Organocatalyzed Cycloadditions Based on the aza-Morita-Baylis-Hillman-type (aza-MBH) and Rauhut-Currier (RC) Proces2013

    • Author(s)
      Takizawa, S.; Sasai, H.
    • Organizer
      The 8th International Conference on Cutting-Edge Organic Chemistry in Asia and The 4th New Phase International Conference on S Cutting-Edge Organic Chemistry in Asia
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      20131125-20131128
  • [Presentation] Acid-Base Organocatalyzed Enantioselective Synthesis of Highly Functionalized Heterocyclic Compounds2013

    • Author(s)
      Takizawa, S.; Nguyen, T. M.-N.; Inoue, N.; Hirata, S.; Sasai, H.
    • Organizer
      10th International Symposium on Carbanion Chemistry
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      20130923-20130926
  • [Presentation] Enantioselective Organocatalyzed Formal [n+2] Cycloaddition of Ketimines2013

    • Author(s)
      Arteaga, F. A.; Takizawa, S.; Yoshida, Y.; Suzuki, M.; Sasai, H.
    • Organizer
      10th International Symposium on Carbanion Chemistry
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      20130923-20130926
  • [Presentation] Enantioselective Organocatalyzed Aza-Morita-Baylis-Hillman (aza-MBH) Reraction of Ketimines2013

    • Author(s)
      Takizawa, S.; Remond, E.; Arteaga, F. A.; Yoshida, Y.; Sridharan, V.; Bayardon, J.; Juge, S.; Sasai, H.
    • Organizer
      15th Asian Chemical Congress
    • Place of Presentation
      Sentosoa, Singapore
    • Year and Date
      20130819-20130823
  • [Presentation] Enantioselective Organocatalyzed aza-MBH Domino Reactions of Ketimine2013

    • Author(s)
      Takizawa, S.; Arteaga, F. A.; Yoshida, Y.; Sasai, H.
    • Organizer
      The 16th International Symposium on Relations between Homogeneous and Heterogeneous Catalysis
    • Place of Presentation
      Sapporo, Japan
    • Year and Date
      20130804-20130809
  • [Presentation] Enantioselective C-C Bond Forming Reactions Using Multi-Functional Organocatalysts: aza-Morita-Baylis-Hillman (aza-MBH) Reaction of Ketimines2013

    • Author(s)
      Takizawa, S.
    • Organizer
      第1回 国際会議 (兼) 第6回 有機触媒シンポジウム
    • Place of Presentation
      Otsu, Japan
    • Year and Date
      20130527-20130528
    • Invited
  • [Presentation] Enantioselective Synthesis of Multifunctional Heterocyclic Compounds via Acid-Base Organocatalysis2013

    • Author(s)
      Takizawa, S.; Nguyen, T. M.-N.; Inoue, N.; Hirata, S.; Sasai, H.
    • Organizer
      7th International Symposium on Acid-Base Catalysis
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      20130512-20130515

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Published: 2015-05-28  

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