Efficient Asymmetric Synthesis of Quasi-Natural Bioactive Compounds Having Contiguous All-Carbon Quaternary Stereocenters

• Project/Area Number: 26410116
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: Nagoya University
• Principal Investigator: Ohmatsu Kohsuke 名古屋大学, 工学研究科(WPI), 特任准教授 (00508997)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 不斉合成 / 反応開発 / 多連続不斉炭素 / キラル配位子 / パラジウム / 効率的不斉合成

Outline of Final Research Achievements

A Pd-catalyzed highly enantio- and diastereoselective [3+2] cycloaddition of 5-vinyloxazolidinones and activated trisubstituted alkenes has been successfully developed. This protocol for the single-step construction of densely functionalized pyrrolidines with three contiguous stereocenters including vicinal quaternary stereocenters depends on the remarkable ability of phosphine ligands possessing a chiral ammonium ion to promote intermolecular cycloaddition reactions with a precise control of absolute stereochemistry. A series of control experiments indicated that a chiral ammonium-phosphine hybrid ligand enabled the individual, yet simultaneous stereocontrol of each chiral center in the annulation reaction.

Research Products

• [Journal Article] A Modular Strategy for the Direct Catalytic Asymmetric α-Amination of Carbonyl Compound (2016)
  • Author(s): Kohsuke Ohmatsu, Yuichiro Ando, Tsubasa Nakashima, Takashi Ooi
  • Journal Title: Chem Volume: 1 Issue: 5 Pages: 802-810
  • DOI: 10.1016/j.chempr.2016.10.012
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Anion Stoichiometry-Dependent Selectivity Enhancement in Ion-Paired Chiral Ligand/Pd Complex-Catalyzed Enantioselective Allylic Alkylation (2016)
  • Author(s): Kohsuke Ohmatsu, Yoshiyuki Hara, Yuya Kusano, Takashi Ooi
  • Journal Title: Synlett Volume: 27 Issue: 07 Pages: 1047-1050
  • DOI: 10.1055/s-0035-1561403
  • Peer Reviewed
• [Journal Article] Palladium-Catalyzed Branch-Selective Decarboxylative Allylation Using Ion-Paired Ligands (2016)
  • Author(s): Yoshiyuki Hara, Yuya Kusano, Kohsuke Ohmatsu, Takashi Ooi
  • Journal Title: Chemistry Letters Volume: 45 Issue: 5 Pages: 552-554
  • DOI: 10.1246/cl.160158
  • NAID: 130005150478
  • Peer Reviewed / Open Access
• [Journal Article] Multiple Absolute Stereocontrol in Pd-Catalyzed [3+2] Cycloaddition of Oxazolidinones and Trisubstituted Alkenes Using Chiral Ammonium-Phosphine Hybrid Ligands (2016)
  • Author(s): Naomichi Imagawa, Yuya Nagato, Kohsuke Ohmatsu, Takashi Ooi
  • Journal Title: Bulletin of the Chemical Society of Japan Volume: 89 Issue: 6 Pages: 649-656
  • DOI: 10.1246/bcsj.20160053
  • NAID: 130005157276
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Design of supramolecular chiral ligands for asymmetric metal catalysis (2015)
  • Author(s): Kohsuke Ohmatsu, Takashi Ooi
  • Journal Title: Tetrahedron Letters Volume: 56 Issue: 16 Pages: 2043-2048
  • DOI: 10.1016/j.tetlet.2015.02.096
  • Acknowledgement Compliant
• [Journal Article] イオン対の活用に基づく新奇なキラル配位子の創製と応用 (2015)
  • Author(s): 大松亨介，大井貴史
  • Journal Title: 有機合成化学協会誌 Volume: 73 Pages: 140-150
  • NAID: 130005129431
  • Acknowledgement Compliant
• [Journal Article] In-Situ Generation of Ion-Paired Chiral Ligands: Rapid Identification of Optimal Ligand for Palladium-Catalyzed Asymmetric Allylation (2014)
  • Author(s): Kohsuke Ohmatsu, Yoshiyuki Hara, Takashi Ooi
  • Journal Title: Chemical Science Volume: 5 Issue: 9 Pages: 3645-3650
  • DOI: 10.1039/c4sc01032a
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Palladium-Catalyzed Asymmetric [3+2] Cycloaddition of 5-Vinyloxazolidinones with Imines Using Chiral Ammonium-Phosphine Hybrid Ligand (2014)
  • Author(s): Kohsuke Ohmatsu, Shinya Kawai, Naomichi Imagawa, Takashi Ooi
  • Journal Title: ACS Catalysis Volume: 4 Issue: 12 Pages: 4304-4306
  • DOI: 10.1021/cs501369z
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Dynamic Kinetic Resolution of N-Unprotected Amino Esters (2017)
  • Author(s): Yuya Nagato, Kohsuke Ohmatsu, Takashi Ooi
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 横浜・神奈川
  • Year and Date: 2017-03-16
• [Presentation] N-Bocオキシインドールの直截的不斉α-ヒドロキシル化反応 (2017)
  • Author(s): 安藤 祐一郎, 大松 亨介, 大井 貴史
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 横浜・神奈川
  • Year and Date: 2017-03-16
• [Presentation] β-ケトエステルおよびα-シアノエステルの直截的不斉α-アミノ化反応 (2017)
  • Author(s): 中島 翼, 大松 亨介, 大井 貴史
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 横浜・神奈川
  • Year and Date: 2017-03-16
• [Presentation] Design of Modular Chiral Ionic Catalysts for Asymmetric Reactions (2016)
  • Author(s): Kohsuke Ohmatsu
  • Organizer: Shibasaki Corokium
  • Place of Presentation: 東京
  • Year and Date: 2016-09-30
  • Invited
• [Presentation] イオン対の特性を活かした不斉触媒の設計と機能創出 (2016)
  • Author(s): 大松 亨介
  • Organizer: 東京農工大学若手講演会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-15
  • Invited
• [Presentation] イオン対の特性を活かした新奇触媒の創製と高難度分子変換反応の開拓 (2016)
  • Author(s): 大松 亨介
  • Organizer: 日本化学会春季年会
  • Place of Presentation: 同志社大学・京田辺キャンパス
  • Year and Date: 2016-03-24
  • Invited
• [Presentation] N-無保護アミノエステルの触媒的ラセミ化反応の開発と応用 (2016)
  • Author(s): 永戸 雄也, 大松 亨介, 大井 貴史
  • Organizer: 日本化学会春季年会
  • Place of Presentation: 同志社大学・京田辺キャンパス
  • Year and Date: 2016-03-24
• [Presentation] キラルオニウム複合型配位子の多連続絶対立体化学制御能を活用した不斉環化付加反応 (2016)
  • Author(s): 今川 直道, 大松 亨介, 大井 貴史
  • Organizer: 日本化学会春季年会
  • Place of Presentation: 同志社大学・京田辺キャンパス
  • Year and Date: 2016-03-24
• [Presentation] 不斉パラジウム触媒反応におけるイオン対型配位子の多様性と可変性の拡張 (2016)
  • Author(s): 草野 雄哉, 大松 亨介, 大井 貴史
  • Organizer: 日本化学会春季年会
  • Place of Presentation: 同志社大学・京田辺キャンパス
  • Year and Date: 2016-03-24
• [Presentation] Design of Small Molecules for Chemistry and Biology (2016)
  • Author(s): Kohsuke Ohmatsu
  • Organizer: The 2nd CSRS-ITbM Joint Workshop
  • Place of Presentation: 理化学研究所・和光
  • Year and Date: 2016-01-07
  • Invited
• [Presentation] Rapid identification of optimal ligand for palladium-catalyzed asymmetric allylations (2015)
  • Author(s): Yoshiyuki Hara, Kohsuke Ohmatsu, Takashi Ooi
  • Organizer: Pacifichem 2015
  • Place of Presentation: Hawaii・America
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Ligand-enabled multiple absolute stereocontrol in palladium-catalyzed [3 + 2] cycloaddition (2015)
  • Author(s): Naomichi Imagawa, Kohsuke Ohmatsu, Takashi Ooi
  • Organizer: Pacifichem 2015
  • Place of Presentation: Hawaii・America
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Catalytic asymmetric carbon-heteroatom bond-forming reactions at α-position of carbonyl compounds (2015)
  • Author(s): Kohsuke Ohmatsu, Yuichiro Ando, Takashi Ooi
  • Organizer: The 39th Naito Conference on The chemistry of organocatalysts
  • Place of Presentation: 札幌
  • Year and Date: 2015-07-06
  • Int'l Joint Research
• [Presentation] Palladium-Catalyzed Asymmetric Construction of Heterocyclic Compounds Bearing Quaternary Stereocenters (2014)
  • Author(s): Naomichi Imagawa, Kohsuke Ohmatsu, Takashi Ooi
  • Organizer: IGER Annual meeting 2014
  • Place of Presentation: Nagoya
  • Year and Date: 2014-12-19
• [Presentation] Rapid Identification of Optimal Ligand for Palladium-Catalyzed Asymmetric Allylation (2014)
  • Author(s): Yoshiyuki Hara, Kohsuke Ohmatsu, Takashi Ooi
  • Organizer: IGER Annual meeting 2014
  • Place of Presentation: Nagoya
  • Year and Date: 2014-12-19
• [Presentation] キラルオニウム複合型パラジウム錯体を用いた5‐ビニルオキサジリジノンとイミンの不斉環化付加反応 (2014)
  • Author(s): 河合 伸弥, 大松 亨介, 大井 貴史
  • Organizer: 第45回中部化学関係学協会支部連合秋季大会
  • Place of Presentation: 春日井・愛知
  • Year and Date: 2014-11-29 – 2014-11-30
• [Presentation] イオン対型キラル配位子を用いた不斉アリル化反応に対する最適触媒の効率的探索法の開発 (2014)
  • Author(s): 原 良行, 大松亨介, 大井貴史
  • Organizer: 第４回CSJフェスタ2014 日本化学会秋季事業
  • Place of Presentation: 船橋
  • Year and Date: 2014-10-14 – 2014-10-16
• [Presentation] 触媒的不斉環化付加反応による二連続不斉四級炭素構築法の開発 (2014)
  • Author(s): 今川 直道, 大松亨介, 大井貴史
  • Organizer: 第４回CSJフェスタ2014 日本化学会秋季事業
  • Place of Presentation: 船橋
  • Year and Date: 2014-10-14 – 2014-10-16
• [Presentation] キラルオニウム複合型パラジウム錯体を用いた光学活性イミダゾリジノンの不斉合成 (2014)
  • Author(s): 河合 伸弥, 大松 亨介, 大井 貴史
  • Organizer: 第31回有機合成化学セミナー
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-17 – 2014-09-19
• [Presentation] In-situ Generation of Ion-Paied Chiral Ligands: Rapid Identification of Optimal Ligand for Palladium-Catalyzed Asymmetric Allylation (2014)
  • Author(s): Yoshiyuki Hara, Kohsuke Ohmatsu, Takashi Ooi
  • Organizer: IGER International Symposium on Chemical Science in Asia
  • Place of Presentation: Nagoya
  • Year and Date: 2014-05-26 – 2014-05-28
• [Presentation] Asymmetric Synthesis of Chiral Small Molecules Containing Contiguous All-Carbon Quaternary Stereocenters (2014)
  • Author(s): Kohsuke Ohmatsu
  • Organizer: The 2nd International Symposium on Transformative Bio-Molesules
  • Place of Presentation: Nagoya
  • Year and Date: 2014-05-12
  • Invited