多点制御型有機触媒の創製を基盤とする同一時空間集積型反応の開発

• Project Area: Organic Synthesis based on Integration of Chemical Reactions. New Methodologies and New Materials
• Project/Area Number: 24106726
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Osaka University
• Principal Investigator: 笹井 宏明 大阪大学, 産業科学研究所, 教授 (90205831)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2013: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 有機分子触媒 / 不斉合成 / パラジウム / スピロビスイソオキサゾリン / パラジウムエノラート / 極性転換 / 四価パラジウム / 環化付加反応 / 不斉 / アザ-MBH / ドミノ反応 / エノン / イミン / 四置換炭素 / 形式的[n+2]環化付加 / 触媒

Research Abstract

我々は、同一時空間集積化を基軸とする効率的な精密有機合成法の創出を目指し、不斉触媒を活用するエナンチオ選択的ドミノ反応の開発を行った。不斉触媒には、酸性および塩基性官能基を同一分子に導入した二重活性化型有機分子触媒、あるいは剛直なスピロ骨格とイソオキサゾリン配位部位を併せ持つユニークなキラル配位子SPRIXを有するPd錯体触媒を適用した。
有機分子触媒を利用するエナンチオ選択的反応では、分子内Rauhut-Currier反応によるα-メチレン-γ-ブチロラクトン類の効率的合成法や、アレン酸エステルとイミンとの形式的環化付加反応によるアゼチジン類やテトラヒドロフラン類の合成を達成した。また、ブルゴーニュ大学Juge教授らとの共同研究により、P-キラルな有機分子触媒を開発し、ケトン由来のイミンであるケチミンを反応基質とするエナンチオ選択的aza-Morita-Baylis-Hillman反応に成功した。
Pd-SPRIX錯体を触媒とする反応開発では、アルキニルシクロヘキサジエノン類の環化反応において、パラジウムエノラート中間体に対して求核剤が反応する世界で初めての極性転換反応を見いだした。
さらに、四価のパラジウムが触媒サイクルに寄与するPd(II)/Pd(IV)触媒反応についてもSPRIXを適用し、ホモアリルアルコールの環化的アセトキシ化による3－オキシテトラヒドロフラン類のエナンチオ選択的合成にも成功した。

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

• [Journal Article] Enantioselective Oxidative-Coupling of Polycyclic Phenols (2014)
  • Author(s): Takizawa, S. ; Kodera, J. ; Yoshida I ; Sako, M. ; Breukers, S. ; Enders, D. ; Sasai, H.
  • Journal Title: Tetrahedron Volume: 70 Issue: 9 Pages: 1786-1793
  • DOI: 10.1016/j.tet.2014.01.017
  • Peer Reviewed
• [Journal Article] Enantioselective Organocatalyzed Formal [4+2] Cycloaddition of Ketimines with Allenoates : Easy Access to a Tetrahydropyridine Framework with a Chiral Tetrasubstituted Stereogenic Carbon Center (2014)
  • Author(s): Takizawa, S. ; Arteaga, F. A. ; Yoshida. Y. ; Suzuki, M. ; Sasai, H.
  • Journal Title: Asian J. Org. Chem. Volume: 3 Issue: 4 Pages: 412-415
  • DOI: 10.1002/ajoc.201300244
  • Peer Reviewed
• [Journal Article] Pd Enolate Umpolung: Cyclative Diacetoxylation of Alkynyl Cyclohexadienones Promoted by Pd-SPRIX Catalyst (2014)
  • Author(s): Takenaka, K.; Mohanta, S. C.; Sasai, H.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 53 Issue: 18 Pages: 4675-4679
  • DOI: 10.1002/anie.201311172
  • Peer Reviewed
• [Journal Article] Vanadium-Catalyzed Enantioselective Friedel-Crafts-Type Reactions (2013)
  • Author(s): Takizawa, S. ; Arteaga, F. A. ; Yoshida. Y. ; Kodera, J. ; Nagata, Y. ; Sasai, H.
  • Journal Title: Dalton Trans. Volume: 42 Issue: 33 Pages: 11787-11790
  • DOI: 10.1039/c2dt32202a
  • Peer Reviewed
• [Journal Article] DFT Study on 5-Endo-Trig-Type Cyclization of 3-Alkenoic Acids Using Pd-SPRIX Catalyst: Importance of the Rigid Spiro Framework for Both Selectivity and Reactivity (2013)
  • Author(s): Gabr, R. K. M.; Hatakeyama, T.; Takenaka, K.; Takizawa, S.; Okada, Y.; Nakamura, M.; Sasai, H.
  • Journal Title: Chem. Eur. J Volume: (in press) Issue: 29 Pages: 9518-9525
  • DOI: 10.1002/chem.201203189
  • Peer Reviewed
• [Journal Article] o-(Hydroxyalkyl)phenyl P-chirogenic phosphines as functional chiral Lewis bases (2013)
  • Author(s): Remond, E.; Bayardon, J.; Takizawa, S.; Rousselin, Y.; Sasai, H.; Juge, S.
  • Journal Title: Org. Lett. Volume: 15 Issue: 8 Pages: 1870-1873
  • DOI: 10.1021/ol400515e
  • Peer Reviewed
• [Journal Article] Carbonylation of Propargyl Carbamates with Palladium(II) Bisoxazoline Catalysts: Efficient Synthesis of 5-Methyl-3(2H)-furanones (2013)
  • Author(s): Kusakabe, T.; Takahashi, T.; Shen, R.; Ikeda, A.; Dhage, Y. D.; Kanno, Y.; Inouye, Y.; Sasai, H.; Mochida, T.; Kato, K.
  • Journal Title: Angew. Chem. Int. Ed. Volume: 52 Issue: 30 Pages: 7845-7849
  • DOI: 10.1002/anie.201303684
  • Peer Reviewed
• [Journal Article] Enantioselective Multicatalytic Synthesis of α-Benzyl-β-hydroxyindan-1-ones (2013)
  • Author(s): Suzuki, T.; Ishizaka, Y.; Ghozati, K.; Zhou, D.-Y.; Asano, K.; Sasai, H
  • Journal Title: Synthesis Volume: (in press) Issue: 15 Pages: 2134-2136
  • DOI: 10.1055/s-0033-1338479
  • Peer Reviewed
• [Journal Article] Pd(II)-SDP-Catalyzed Enantioselective 5-Exo-Dig Cyclization of γ-Alkynoic Acids: Application to the Synthesis of Functionalized Dihydrofuran-2(3H)-ones Containing a Chiral Quaternary Carbon Center (2013)
  • Author(s): Sridharan, V.; Fan, L.; Takizawa, S.; Suzuki, T.; Sasai, H.
  • Journal Title: Org. Biomol. Chem. Volume: 11 Issue: 35 Pages: 5936-5943
  • DOI: 10.1039/c3ob41103f
  • Peer Reviewed
• [Journal Article] P-Chirogenic Organocatalysts : Application to the aza-Morita-Baylis-Hillman (aza-MBH) Reaction of Ketimines (2013)
  • 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 Issue: 75 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 center (2013)
  • Author(s): Takizawa, S.; Arteaga, F. A.; Yoshida, Y.; Suzuki, M.; Sasai, H.
  • Journal Title: Org. Lett. Volume: 15 Issue: 16 Pages: 4142-4145
  • DOI: 10.1021/ol401817q
  • Peer Reviewed
• [Journal Article] Chiral Bifunctional Organocatalysts Bearing a 1,3-Propanediamine Unit for the aza-MBH Reaction (2013)
  • Author(s): Hirata, S. ; Tanaka, K. ; Matsui, K. ; Arteaga, F. A. ; Yoshida. Y. ; Takizawa, S. ; Sasai, H.
  • Journal Title: Tetrahedron : Asymmetry Volume: 24 Issue: 19 Pages: 1189-1192
  • DOI: 10.1016/j.tetasy.2013.08.005
  • Peer Reviewed
• [Journal Article] Enantioselective Pd(II)/Pd(IV) Catalysis Utilizing SPRIX Ligand: Efficient Construction of Chiral 3-Oxy-Tetrahydrofurans (2013)
  • Author(s): Takenaka, K.; Dhage, Y. D.; Sasai, H.
  • Journal Title: Chem. Commun. Volume: 49 Issue: 95 Pages: 11224-11226
  • DOI: 10.1039/c3cc44797a
  • Peer Reviewed
• [Journal Article] Facile Synthesis of a-Methylidene-y-Butyrolactones : Intramolecular Rauhut-Currier Reaction Promoted by Chiral Acid-Base Organocatalysts (2013)
  • Author(s): Takizawa, S. ; Nguyen, T. M.-N. ; Grossmann, A. ; Enders, D. ; Sasai, H.
  • Journal Title: Tetrahedron Volume: 69 Issue: 3 Pages: 1202-1209
  • DOI: 10.1016/j.tet.2012.11.046
  • Peer Reviewed
• [Journal Article] Enantioselective Synthesis of a-Alkylidene-y-Butyrolactones : Intramolecular Rauhut-Currior Reaction Promoted by Acid/Base Organocatalysts (2012)
  • Author(s): Takizawa, S. ; Nguyen, T. M.-N. ; Grossmann, A. ; Enders, D. ; Sasai H.
  • Journal Title: Angewandte Chemie International Edition Volume: 51 Issue: 22 Pages: 5423-5426
  • DOI: 10.1002/anie.201201542
  • Peer Reviewed
• [Journal Article] Design, and Synthesis of Spiro Bis(l, 2, 3-triazolium) Salts As Chiral Ionic Liquids (2012)
  • Author(s): Yoshida, Y. ; Takizawa, S. ; Sasai H
  • Journal Title: Tetrahedron : Asymmetry Volume: 23 Issue: 11-12 Pages: 843-851
  • DOI: 10.1016/j.tetasy.2012.06.007
  • Peer Reviewed
• [Presentation] 有機分子触媒によるジエノンと2,3－ブタジエン酸エステルとを基質とするエナンチオ選択的形式的[3+2]環化反応の開発 (2014)
  • Author(s): 鈴木通恭、F. A. Arteaga、T. M.-N. Nguyen、滝澤忍、笹井宏明
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋
• [Presentation] ビス1,2,3－トリアゾールユニットを有するヘテロヘリセンのエナンチオ選択的合成と不斉触媒への応用 (2014)
  • Author(s): 吉田泰志、滝澤忍、笹井宏明
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋
• [Presentation] Enantioselective Organocatalyzed Synthesis of Cyclobutanes via Formal [2+2] Cycloaddition (2014)
  • Author(s): F. A. Arteaga、滝澤忍、笹井宏明
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋
• [Presentation] Umpolung Reactivity of Pd Enolate: Cyclative Diacetoxylation of Alkynyl Cyclohexadienones Catalyzed by Pd-SPRIX (Oral) (2013)
  • Author(s): Takenaka, K.; Mohanta, S. C.; Takizawa, S.; Sasai, H.
  • Organizer: 245th ACS National Meeting
  • Place of Presentation: New Orleans, USA
• [Presentation] Novel Catalytic Reaction Promoted by Pd-SPRIX Complex (2013)
  • Author(s): Takenaka, K.; Mohanta, S. C.; Dhage, Y. D.; Takizawa, S.; Sasai, H.
  • Organizer: First Osaka University-EPFL International Symposium
  • Place of Presentation: Osaka, Japan
• [Presentation] Enantioselective Organocatalyzed Aza-Morita-Baylis-Hillman (Aza-MBH) Reaction of Ketimines (2012)
  • Author(s): Takizawa, S.; Arteaga, A. F.; Yoshida, Y.; Vellaisamy, S.; Reacute;mond, E.; Bayardon, J.; Jugeacute;, S.; Sasai, H.
  • Organizer: Aachen-Osaka Symposium “Biological and Chemical Methods for Selective Catalysis”
  • Place of Presentation: Aachen, Germany
  • Year and Date: 2012-12-03
• [Presentation] Design and Synthesis of Organocatalysts Bearing Spiro Backbone (2012)
  • Author(s): Fan, L.; Takizawa, S.; Sasai, H.
  • Organizer: Aachen-Osaka Symposium “Biological and Chemical Methods for Selective Catalysis”
  • Place of Presentation: Aachen, Germany
  • Year and Date: 2012-12-03
• [Presentation] Dual Activation in Asymmetric Organocatalyses (2012)
  • Author(s): Sasai, H.
  • Organizer: 17th Malaysian Chemical Congress (17MCC) 2012
  • Place of Presentation: Kuala Lumpur, Malaysia
  • Year and Date: 2012-10-15
  • Invited
• [Presentation] Development of Enantioselective Carbon-Carbon Bond Forming Reactions Using Multi-functional Organocatalyst (2012)
  • Author(s): Sasai, H.
  • Organizer: International Conference on Functional Organic Materials and Related Devices
  • Place of Presentation: Hsinchu, Taiwan
  • Year and Date: 2012-06-16
  • Invited
• [Presentation] Exploring Novel Enantioselective Domino Reactions Promoted by Bifunctional Organocatalysts (2012)
  • Author(s): Sasai, H.
  • Organizer: International Symposium on Organic Synthesis and Drug Development (ISOSDD2012)
  • Place of Presentation: Changzhou, China
  • Year and Date: 2012-05-20
  • Invited
• [Book] Domino Reactions: Concepts for Efficient Organic Synthesis, Chapter 11 (2014)
  • Author(s): Takizawa, S. Sasai, H.
  • Total Pages: 44
  • Publisher: Wiley-VCH
• [Remarks] 大阪大学産業科学研究所機能物質化学研究分野笹井研究室
  • URL: http://www.sanken.osaka-u.ac.jp/labs/soc/socmain.html
• [Remarks] 大阪大学産業科学研究所機能物質科学研究分野ホームページ
  • URL: http://www.sanken.osaka-u.ac.jp/labs/soc/socmain.html