Catalytic Asymmetric Reactions of Alkenes Activated by Two Electron-Withdrawing Groups and Their Applications to Efficient Enantioselective Total Syntheses

• Project/Area Number: 25293003
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Waseda University
• Principal Investigator: Nakada Masahisa 早稲田大学, 理工学術院, 教授 (50198131)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2013: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 不斉触媒反応 / 付加環化 / Michael反応 / 生物活性天然物 / 不斉全合成

Outline of Final Research Achievements

A synthetic method of alpha-alkylidene-beta-oxo imides and their catalytic asymmetric reactions ([4+2] and [2+2]cycloadditions, Mukaiyama-Michael reaction, Hosomi-Sakurai-Michael reaction, and Friedel-Crafts reaction) have been successfully developed. alpha-alkylidene-beta-oxo phosphonates were found to show the similar property as those of alpha-alkylidene-beta-oxo imides in Mukaiyama-Michael reaction. Using alkenes doubly activated by ketone and ester, an enantioselective total synthesis of (R)-homosarcomnycin, and a first enantioselective total synthesis and structural elucidation of (-)-bucidarasin A and C have been successfully achieved.

Research Products

• [Journal Article] A Highly Stereoselective Intramolecular Diels-Alder Reaction for Construction of the AB-Ring Moiety of Bruceantin (2015)
  • Author(s): Usui, K.; Suzuki, T.; Nakada, M.
  • Journal Title: Tetrahedron Lett. Volume: 56 Issue: 10 Pages: 1247-1251
  • DOI: 10.1016/j.tetlet.2015.01.139
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Highly Enantioselective Catalytic Friedel–Crafts Reactions of Cyclic α-Alkylidene β-Oxo Imides (2015)
  • Author(s): Oyama, H.; Nakada, M.
  • Journal Title: Tetrahedron: Asymmetry Volume: 26 Issue: 4 Pages: 195-202
  • DOI: 10.1016/j.tetasy.2015.01.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enantioselective Total Synthesis of (+)-Bucidarasins A and C (2015)
  • Author(s): Usui, K.; Nakada, M.
  • Journal Title: Heterocycles Volume: 91 Issue: 2 Pages: 332-350
  • DOI: 10.3987/com-14-13161
  • NAID: 40020365649
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Highly Enantioselective Catalytic Asymmetric Mukaiyama–Michael Reactions of Cyclic α-Alkylidene β-Oxo Imides (2015)
  • Author(s): Oyama, H.; Orimoto, K.; Niwa, T.; Nakada, M.
  • Journal Title: Tetrahedron: Asymmetry Volume: 26 Issue: 5-6 Pages: 262-270
  • DOI: 10.1016/j.tetasy.2015.01.012
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enantioselective Total Synthesis of (+)-Bucidarasin C and Elucidation of the Absolute Configuration (2014)
  • Author(s): Usui, K.; Kanbe, M.; Nakada, M.
  • Journal Title: Org. Lett. Volume: 16 Issue: 18 Pages: 4734-4737
  • DOI: 10.1021/ol502129u
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Highly Enantioselective Catalytic Asymmetric [2+2] Cycloadditions of Cyclic -Alkylidene -Oxo Imides with Ynamides (2014)
  • Author(s): Enomoto, K.; Oyama, H.; Nakada, M.
  • Journal Title: Chem.-Eur. J. Volume: 21 Issue: 7 Pages: 2798-2802
  • DOI: 10.1002/chem.201406189
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Preparation of Imides via the Palladium-Catalyzed Coupling Reaction of Organostannanes with Methyl N-[Methoxy(methylthio)methylene]carbamate (2013)
  • Author(s): Orimoto, K.; Tomizawa, T. Oyama, H.; Namera, Y.; Niwa, T.; Nakada, M.
  • Journal Title: Heterocycles Volume: 87(4) Issue: 4 Pages: 827-840
  • DOI: 10.3987/com-13-12662
  • Peer Reviewed
• [Presentation] フロー法を用いたハロゲン‐リチウム交換反応によるα-アルキリデンβ-オキソリチウム種の発生と反応 (2016)
  • Author(s): 小室勝洋、永木愛一郎、吉田潤一、中田雅久
  • Organizer: 日本化学会第96春季年会（2016）
  • Place of Presentation: 京都
  • Year and Date: 2016-03-24
• [Presentation] Asymmetric Total Synthesis of Bioactive Polycyclc Natural Products (2015)
  • Author(s): Masahisa Nakada
  • Organizer: the 25th Symposium on Optically Active Compounds
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2015-11-27
  • Int'l Joint Research / Invited
• [Presentation] Catalytic Asymmetric [2+2] Cycloadditions of α-Alkylidene β-Oxo Imides (2015)
  • Author(s): ENOMOTO, Kazuaki; OYAMA, Harufumi; NAKADA, Masahisa
  • Organizer: 日本化学会 第95春季年会（2015）
  • Place of Presentation: 千葉
  • Year and Date: 2015-03-28
• [Presentation] α-アルキリデンβ-オキソイミドの触媒的不斉フリーデル－クラフツ反応 (2015)
  • Author(s): 大山 陽文・榎本 和朗・中田 雅久
  • Organizer: 日本化学会 第95春季年会（2015）
  • Place of Presentation: 千葉
  • Year and Date: 2015-03-28
• [Presentation] clerodane型ジテルペンbucidarasin AおよびCの初の不斉全合成と絶対配置決定 (2014)
  • Author(s): 臼井研二, 神戸美咲, 中田雅久
  • Organizer: 第56回天然有機化合物討論会
  • Place of Presentation: 徳島
  • Year and Date: 2014-10-16
• [Presentation] Catalytic Asymmetric Michael Reaction of Cyclic Unsaturated Keto Phosphonate (2014)
  • Author(s): Kotaro NAGATANI, Atsushi MINAMI, and Masahisa NAKADA
  • Organizer: the XXVI International Conference on Organometallic Chemistry (ICOMC 2014)
  • Place of Presentation: Sapporo, Hokkaido, Japan
  • Year and Date: 2014-07-15
• [Presentation] Highly Enantioselective Catalytic Asymmetric Reactions of Hydrogen-Bonded α-Alkylidene β-Keto Imides (2014)
  • Author(s): Harufumi OYAMA, Kazuaki ENOMOTO, Kohei ORIMOTO, and Masahisa NAKADA
  • Organizer: the XXVI International Conference on Organometallic Chemistry (ICOMC 2014)
  • Place of Presentation: Sapporo, Hokkaido, Japan
  • Year and Date: 2014-07-14
• [Presentation] α-アルキリデンβ-ケトイミドの不斉触媒反応への活用
  • Author(s): 大山 陽文,折本 浩平,中田 雅久
  • Organizer: 第65回有機合成化学協会関東支部シンポジウム（新潟シンポジウム）
  • Place of Presentation: 新潟薬科大学（新潟）
• [Presentation] Catalytic Asymmetric Reactions of α-Alkylidene β-Oxo Imides
  • Author(s): Harufumi Oyama, Masahisa Nakada
  • Organizer: International Symposium on “Integration of Chemistry and Bioscience”
  • Place of Presentation: 早稲田大学西早稲田キャンパス（東京都）
• [Presentation] ent-kaurane類の効率的全合成研究
  • Author(s): 藤井 友博,中田雅久
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋大学（愛知県）
• [Presentation] α－アルキリデン β－ケトイミドを活用する触媒的不斉マイケル反応の開発
  • Author(s): 大山 陽文,折本 浩平,中田 雅久
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋大学（愛知県）
• [Presentation] α－アルキリデン β－ケトイミドの触媒的不斉 [2+2] 付加環化反応
  • Author(s): 大山 陽文,榎本 和朗,中田 雅久
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋大学（愛知県）
• [Presentation] 環状不飽和ケトリン酸エステルの触媒的不斉Michael反応
  • Author(s): 永谷 幸太郎,南 篤志,中田 雅久
  • Organizer: 日本化学会第94春季年会
  • Place of Presentation: 名古屋大学（愛知県）
• [Remarks] 発表論文 PUBLICATIONS
  • URL: http://www.chem.waseda.ac.jp/nakada/publications.html
• [Remarks] PAPERS
  • URL: http://www.chem.waseda.ac.jp/nakada/e-publications.html
• [Remarks] 中田雅久研究室ホームページ
  • URL: http://www.chem.waseda.ac.jp/nakada/