A sustainable and enantioselective process based on chiral spiro-type catalysis

• Project/Area Number: 24590009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Osaka University
• Principal Investigator: TAKIZAWA Shinobu 大阪大学, 産業科学研究所, 准教授 (50324851)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 不斉 / スピロ / 環境調和 / 触媒 / 炭素-炭素結合形成 / キラル / エナンチオ選択的 / 環境低負荷型 / 四置換炭素 / 合成 / イオン性液体

Outline of Final Research Achievements

Chiral ligands and organocatalysts with a spiro skeleton have received considerable attention in asymmetric catalysis because of their unique structural properties and high asymmetric induction efficiency. However, enantioselective synthesis of optically pure spirobicyclic compounds remains a formidable task because the chiral catalysts must control not only the enantiodiscrimination but also the formation of the quaternary carbon center. We have developed the facile synthesis of chiral spirobicycles through the Pd-catalyzed intramolecular α-arylation of α-substituted cyclic ketones. The absolute configuration of spirocyclic ketone was assigned as S by X-ray analysis.

Research Products

• [Journal Article] Pd-catalyzed enantioselective intramolecular α-arylation of α-substituted cyclic ketones: Facile synthesis of functionalized chiral spirobicycles (2015)
  • Author(s): L. Fan, S. Takizawa, Y. Takeuchi, K. Takenaka, H. Sasai
  • Journal Title: Org. Biomol. Chem. Volume: 13 Issue: 17 Pages: 4837-4840
  • DOI: 10.1039/c5ob00382b
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Vanadium in asymmetric synthesis: Emerging concepts in catalyst design and applications (2015)
  • Author(s): S. Takizawa, H. Groger, H. Sasai
  • Journal Title: Chem. Eur. J. Volume: 21 Issue: 25 Pages: 8992-8997
  • DOI: 10.1002/chem.201406444
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] C3-Symmetric chiral trisimidazoline-catalyzed Friedel-Crafts (FC)-type reaction (2014)
  • Author(s): Takizawa, Shinobu; Hirata, Shuichi; Murai, Kenichi; Fujioka, Hiromichi; Sasai, Hiroaki
  • Journal Title: Organic & Biomolecular Chemistry Volume: 12 Issue: 31 Pages: 5827-5830
  • DOI: 10.1039/c4ob00925h
  • Peer Reviewed
• [Journal Article] Facile regio- and stereo-selective metal-free synthesis of all-carbon tetrasubstituted alkenes bearing a C(sp3)-F unit via dehydroxyfluorination of Morita-Baylis-Hillman (MBH) adducts (2014)
  • Author(s): S. Takizawa, F. A. Arteaga, K. Kishi, S. Hirata, H. Sasai
  • Journal Title: Org. Lett. Volume: 16 Issue: 16 Pages: 4162-4165
  • DOI: 10.1021/ol501855m
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enantioselective Acid-Base Organocatalyzed Domino Reactions Based on aza-Morita-Baylis-Hillman Process (2014)
  • Author(s): 滝澤忍, 笹井宏明
  • Journal Title: Journal of Synthetic Organic Chemistry, Japan Volume: 72 Issue: 7 Pages: 781-796
  • DOI: 10.5059/yukigoseikyokaishi.72.781
  • NAID: 130004679609
  • ISSN: 0037-9980, 1883-6526
  • Peer Reviewed / Acknowledgement Compliant
• [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] 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] 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] 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] 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] 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] 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] 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] 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] 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): R. K. Gabr, T. Hatakeyama, K. Takenaka, S. Takizawa, Y. Okada, M. Nakamura, H. Sasai
  • Journal Title: Chem. Eur. J. Volume: 19
  • 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] Stereoselective Construction of Chiral Tetrasubstituted Carbon Stereogenic Centers Via Organocatalytic Rauhut-Currier Reaction (2015)
  • Author(s): 滝澤忍，笹井宏明
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（千葉）
  • Year and Date: 2015-03-26 – 2015-03-29
  • Invited
• [Presentation] Development of Enantioselective Organocatalyzed Formal [n+2] Cycloaddition of Allenic Ester with Olefins (2015)
  • Author(s): 吉田泰志、滝澤忍、Fernando Arteaga-Arteaga、岸鉄馬、笹井宏明
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（千葉）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] Vanadium(V) Complex-Catalyzed Enantioselective Synthesis of Oxa[9]helicene (2015)
  • Author(s): 佐古真、滝澤忍、辻原哲也、吉田泰志、小寺純平、河野富一、笹井宏明
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（千葉）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] Enantioselective Rauhut-Currier Reaction Promoted by an Immobilized Organocatalyst (2015)
  • Author(s): 平田修一、岸鉄馬、滝澤忍、笹井宏明
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（千葉）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] Enantioselective Synthesis of Hetero Helicenes Bearing 1,2,3-Triazole Units (2015)
  • Author(s): 坂井智弘、吉田泰志、滝澤忍、笹井宏明
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（千葉）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] Enantioselective Synthesis of Chiral Spiro Compounds and Their Applications to Organocatalysis (2015)
  • Author(s): 武内芳樹、Lulu Fan、滝澤忍、笹井宏明
  • Organizer: 日本化学会第95春季年会
  • Place of Presentation: 日本大学（千葉）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] パラジウム触媒を用いるアルケニルオキシムのエナンチオ選択的環化―環化付加反応 (2015)
  • Author(s): Mohamed A. Abozeid、滝澤忍、笹井宏明
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸学院大学（兵庫）
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 有機分子触媒を用いるエナンチオ選択的分子内Rauhut-Currier反応によるα-メチリデン-γ-ブチロラクタムの効率的合成 (2014)
  • Author(s): 滝澤忍、岸鉄馬、Fernando Arteaga-Arteaga、笹井宏明
  • Organizer: 第64回日本薬学会近畿支部総会・大会
  • Place of Presentation: 京都薬科大学（京都）
  • Year and Date: 2014-10-11
• [Presentation] Enantioselective C-C Bond Forming Reactions Using Vanadium(V) Catalysts (2014)
  • Author(s): 滝澤忍、辻原哲也、小寺純平、吉田泰志、佐古真、河野富一、笹井宏明
  • Organizer: 第61回有機金属化学討論会
  • Place of Presentation: 九州大学（福岡）
  • Year and Date: 2014-09-23 – 2014-09-25
• [Presentation] 有機触媒を用いる形式的環化付加反応とキラル四置換炭素を有する複素環合成への展開 (2014)
  • Author(s): 滝澤忍、Fernando Arteaga-Arteaga、吉田泰志、鈴木通恭、Tue M.-N. Nguyen、笹井宏明
  • Organizer: 第44回複素環化学討論会
  • Place of Presentation: 札幌市民ホール（北海道）
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] Organocatalyzed Enantioselective Reactions of Ketimines with Allenoates (2014)
  • Author(s): Shinobu Takizawa, Fernando A. Arteaga, Yasushi Yoshida, Michitaka Suzuki, Hiroaki Sasai
  • Organizer: Aachen-Osaka Joint Symposium
  • Place of Presentation: Aachen, Germany
  • Year and Date: 2014-09-03 – 2014-09-05
• [Presentation] Enantioselective C-C Bond Forming Reactions Catalyzed by Vanadium(V) Complex (2014)
  • Author(s): Makoto Sako, Shinobu Takizawa, Yasushi Yoshida, Junpei Kodera, Hiroaki Sasai
  • Organizer: Aachen-Osaka Joint Symposium
  • Place of Presentation: Aachen-Osaka Joint Symposium
  • Year and Date: 2014-09-03 – 2014-09-05
• [Presentation] 四置換オレフィンの簡便かつメタルフリーな立体選択的合成法の開発 (2014)
  • Author(s): 岸鉄馬、Fernando Arteaga-Arteaga、平田修一、滝澤忍、笹井宏明
  • Organizer: 第34回有機合成若手セミナー
  • Place of Presentation: 大阪大学豊中キャンパス（大阪）
  • Year and Date: 2014-08-05
• [Presentation] 5価のバナジウム触媒を用いるエナンチオ選択的C-C結合形成反応の開発と応用 (2014)
  • Author(s): 坂井智弘、滝澤忍、小寺純平、吉田泰志、佐古真、笹井宏明
  • Organizer: 第34回有機合成若手セミナー
  • Place of Presentation: 大阪大学豊中キャンパス（大阪）
  • Year and Date: 2014-08-05
• [Presentation] 不斉有機分子触媒を用いるエナンチオ選択的aza-MBH型ドミノ反応の開発 (2014)
  • Author(s): 平田修一、滝澤忍、井上直人、Fernando Arteaga-Arteaga、吉田泰志、鈴木通恭、笹井宏明
  • Organizer: 日本プロセス化学会2014サマーシンポジウム
  • Place of Presentation: タワーホール船堀（東京）
  • Year and Date: 2014-07-31 – 2014-08-01
• [Presentation] Enantioselective Synthesis of Chiral Spiro Compounds and Their Applications to Organocatalysis (2014)
  • Author(s): Y. Takeuchi, L. Fan, S. Takizawa, H. Sasai
  • Organizer: The 26th International Conference on Organometallic Chemistry (ICOMC2014)
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2014-07-13 – 2014-07-18
• [Presentation] 触媒的不斉連続反応によるキラルビルディングブロックの創出 (2014)
  • Author(s): 滝澤忍
  • Organizer: 第27回インターフェックスジャパン
  • Place of Presentation: 東京ビッグサイト（東京)
  • Year and Date: 2014-07-02 – 2014-07-04
• [Presentation] 多機能有機分子触媒を用いるエナンチオ選択的ドミノ反応の開発 (2014)
  • Author(s): 滝澤忍
  • Organizer: 分子活性化－有機分子触媒合同シンポジウム
  • Place of Presentation: 北海道大学（北海道）
  • Year and Date: 2014-06-20 – 2014-06-21
• [Presentation] ヘリセン及びヘリセン様化合物の効率的不斉合成法の開発 (2014)
  • Author(s): 滝澤忍、吉田泰志、小寺純平、佐古真、土井貴裕、笹井宏明
  • Organizer: Symposium on Molecular Chirality 2014
  • Place of Presentation: 仙台国際センター（宮城）
  • Year and Date: 2014-06-06 – 2014-06-07
• [Presentation] Catalytic Enantioselective Synthesis of Spiro Compounds and Their Applications to Asymmetric Catalysis (2014)
  • Author(s): Fan, L.; Takeuchi, Y.; Takizawa, S.; Sasai, H.
  • Organizer: The 17th SANKEN International Symposium
  • Place of Presentation: Osaka, Japn
• [Presentation] "Recent Progress in Pd-SPRIX Catalyzed Enantioselective Reactions (2013)
  • Author(s): Takenaka, K.; Dhage, Y. D.; Mohanta, S. C.; Takizawa, S.; Sasai, H.
  • Organizer: The 8th International Symposium on Integrated Synthesis
  • Place of Presentation: Nara, Japan
• [Presentation] Recent Progress in Pd-SPRIX Catalyses (2013)
  • Author(s): Takenaka, K.; Mohanta, S. C.; Dhage, Y. D.; 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
• [Presentation] Catalytic Enantioselective Synthesis of Chiral Spiro[4.4]nonane Derivatives and Their Applications to Asymmetric Catalysis (2013)
  • Author(s): Fan, L.; Takizawa, S.; Sasai, H.
  • Organizer: 25th International Symposium on Chirality
  • Place of Presentation: Shanghai, China
• [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 Cyclization of 4-Alkenoic Acids via an Oxidative Allylic C-H Esterification (2013)
  • Author(s): Akita, M.; Tanigaki, Y.; Takenaka, K.; Takizawa, S.; Sasai, H.
  • Organizer: 245th ACS National Meeting
  • Place of Presentation: New Orleans, USA
• [Presentation] Umpolung Reactivity of Pd Enolate: Cyclative Diacetoxylation of Alkynyl Cyclohexadienones Catalyzed by Pd-SPRIX (2013)
  • Author(s): Takenaka, K.; Mohanta, S. C.; Takizawa, S.; Sasai, H.
  • Organizer: 245th ACS National Meeting
  • Place of Presentation: New Orleans, USA
• [Presentation] Enantioselective C-C Bond Forming Reactions Using Multi-Functional Organocatalysts: aza-Morita-Baylis-Hillman (aza-MBH) Reaction of Ketimines (2013)
  • Author(s): S. Takizawa
  • 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
• [Presentation] Development of New Efficient Synthesis Method of Spiro Bis(1,2,3-triazole)s and Their Applications (2013)
  • Author(s): Yoshida, Y.; Takizawa, S.; Sasai, H.
  • Organizer: Aachen-Osaka Symposium “Biological and Chemical Methods for Selective Catalysis”
  • Place of Presentation: Osaka, Japan
• [Presentation] Enantioselective Pd(II)/Pd(IV) Catalysis Using SPRIX Ligand: Efficient Synthesis of Chiral Tetrahydrofuran Derivatives (2013)
  • Author(s): Takenaka, K.; Dhage, Y. D.; Takizawa, S.; Sasai, H.
  • Organizer: Aachen-Osaka Symposium “Biological and Chemical Methods for Selective Catalysis”
  • Place of Presentation: Osaka, Japan
• [Presentation] Study on Asymmetric Environment of SPRIX Ligand (2012)
  • Author(s): Lin, X.; Takenaka, K.; Takizawa, S.; Sasai, H.
  • Organizer: Aachen-Osaka Symposium “Biological and Chemical Methods for Selective Catalysis
  • Place of Presentation: Aachen, Germany
• [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
• [Presentation] Umpolung Reactivity of Pd Enolate: Cyclative Diacetoxylation of Alkynyl Cyclohexadienones Catalyzed by Pd-SPRIX (2012)
  • Author(s): Takenaka, K.; Mohanta, S. C.; Takizawa, S.; Sasai, H.
  • Organizer: The 6th Kansai-CMDS Meeting on OMCOS 2012
  • Place of Presentation: Gangwon-do, Korea
  • Invited
• [Book] In Domino Reactions: Concepts for Efficient Organic Synthesis (2014)
  • Author(s): S. Takizawa, H. Sasai
  • Total Pages: 648
  • Publisher: Wiley-VCH Verlag GmbH & Co. KGaA
• [Remarks] 大阪大学 産業科学研究所 機能物質化学研究分野
  • 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