Triphosphine ligand-enabled iron catalysis

• Project Area: Precise Formation of a Catalyst Having a Specified Field for Use in Extremely Difficult Substrate Conversion Reactions
• Project/Area Number: 18H04238
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: イリエシュ ラウレアン 国立研究開発法人理化学研究所, 環境資源科学研究センター, チームリーダー (40569951)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: organic synthesis / catalysis / 合成化学 / 有機合成

Outline of Annual Research Achievements

This project aims at the creation of a ligand that can control the reactivity of organoiron species and achieve an efficient and versatile iron catalyst for organic synthesis, surpassing precious metal catalysis. We discovered that an iron/diphosphine catalyst, in the presence of a diorganozinc base and a mild dichloroalkane oxidant enables the stoichiometric cross-coupling of aromatic amides with heteroarenes. The cross-coupling of two different C-H substrates is especially difficult because of competing homocoupling, and typically a large excess of one of the coupling partners must be used; however, the iron catalyst enabled the cross-coupling with perfect selectivity, and homocoupling of the starting materials was not observed at all. The reaction could also be applied to efficient multifold C-H cross-coupling. For example, three C-H bonds in a tris-thiophene molecule could be coupled with three amide molecules’ C-H bonds to create three new C-C bonds in almost quantitative yield. Mechanistic studies suggested that directed C-H activation of the amide takes place first, then the resulting iron intermediate activates the C-H bond of the heteroarene in a reversible fashion. Preliminary results showed that electron-deficient arenes such as chlorobenzene can also be used as the reaction partner.

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Chromium(III)-Catalyzed C(sp2)-H Alkynylation, Allylation, and Naphthalenation of Secondary Amides with Trimethylaluminum as Base (2020)
  • Author(s): Chen Mengqing, Doba Takahiro, Sato Takenari, Razumkov Hlib, Ilies Laurean, Shang Rui, Nakamura Eiichi
  • Journal Title: Journal of the American Chemical Society Volume: 142 Issue: 10 Pages: 4883-4891
  • DOI: 10.1021/jacs.0c00127
  • Peer Reviewed / Open Access
• [Journal Article] Earth‐Abundant Metals in Catalysis (2020)
  • Author(s): Ilies Laurean, Thomas Stephen P., Tonks Ian A.
  • Journal Title: Asian Journal of Organic Chemistry Volume: 9 Issue: 3 Pages: 324-325
  • DOI: 10.1002/ajoc.202000111
  • Open Access / Int'l Joint Research
• [Journal Article] Homocoupling-free iron-catalysed twofold C-H activation/cross-couplings of aromatics via transient connection of reactants (2019)
  • Author(s): Takahiro Doba, Tatsuaki Matsubara, Laurean Ilies, Rui Shang, Eiichi Nakamura
  • Journal Title: Nature Catalysis Volume: 2 Issue: 5 Pages: 400-406
  • DOI: 10.1038/s41929-019-0245-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Silylation of Aryl Halides with Monoorganosilanes Activated by Lithium Alkoxide (2018)
  • Author(s): Yoshida Takumi、Ilies Laurean、Nakamura Eiichi
  • Journal Title: Organic Letters Volume: 20 Issue: 10 Pages: 2844-2847
  • DOI: 10.1021/acs.orglett.8b00818
  • Peer Reviewed
• [Journal Article] Iron-Catalyzed Synthesis of Indenones through Cyclization of Carboxamides with Alkynes (2018)
  • Author(s): Ilies Laurean、Arslanoglu Yasin、Matsubara Tatsuaki、Nakamura Eiichi
  • Journal Title: Asian Journal of Organic Chemistry Volume: 7 Issue: 7 Pages: 1327-1329
  • DOI: 10.1002/ajoc.201800200
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Synthesis of Esomeprazole and Related Proton Pump Inhibitors through Iron-Catalyzed Enantioselective Sulfoxidation (2018)
  • Author(s): Nishiguchi Shigenobu、Izumi Takuhiro、Kouno Takayoshi、Sukegawa Junpei、Ilies Laurean、Nakamura Eiichi
  • Journal Title: ACS Catalysis Volume: 8 Issue: 10 Pages: 9738-9743
  • DOI: 10.1021/acscatal.8b02610
  • Peer Reviewed
• [Journal Article] Iron-Catalyzed Directed Alkylation of Carboxamides with Olefins via a Carbometalation Pathway (2018)
  • Author(s): Ilies Laurean、Zhou Yi、Yang Haotian、Matsubara Tatsuaki、Shang Rui、Nakamura Eiichi
  • Journal Title: ACS Catalysis Volume: 8 Issue: 12 Pages: 11478-11482
  • DOI: 10.1021/acscatal.8b03967
  • Peer Reviewed
• [Presentation] C-H Activation with Earth-Abundant Metals (2020)
  • Author(s): Ilies, L.
  • Organizer: Nanyang Research Conference on Synthetic Chemistry and Catalysis
  • Int'l Joint Research / Invited
• [Presentation] Iron-catalyzed C-H homocoupling of thiophene compounds (2020)
  • Author(s): Doba, T.; Ilies, L.; Shang, R.; Nakamura, E.
  • Organizer: 日本化学会 第100春季年会
• [Presentation] Multikilogram-Scale Synthesis of Esomeprazole Using Enantioselective Iron Catalysis (2019)
  • Author(s): Nishiguchi, S.; Izumi, T.; Kouno, T.; Sukegawa, J.; Ilies, L.; Nakamura E.
  • Organizer: ACS National Meeting
  • Int'l Joint Research
• [Presentation] 鉄触媒を用いた反応開発 (2019)
  • Author(s): イリエシュ ラウレアン
  • Organizer: 第6回 辰巳午会化学シンポジウム
  • Invited
• [Presentation] C-H Activation Using Base Metal Catalysis (2019)
  • Author(s): Ilies L.
  • Organizer: The 47th Naito Conference on C-H Bond Activation and Transformation
  • Int'l Joint Research / Invited
• [Presentation] Multifold C-H Activation Using Iron Catalysis (2019)
  • Author(s): Ilies L.
  • Organizer: Hokkaido Summer Symposium 2019 on Catalysis for Organic Synthesis
  • Invited
• [Presentation] 普遍金属を触媒とする反応開発の苦悩と歓喜 (2019)
  • Author(s): イリエシュ ラウレアン
  • Organizer: 理研シンポジウム：第14回有機合成化学のフロンティア
  • Invited
• [Presentation] Homocoupling-free iron-catalyzed oxidative cross-coupling of aromatics via transient connection of reactants (2019)
  • Author(s): Takahiro Doba, Tatsuaki Matsubara, Laurean Ilies, Rui Shang, Eiichi Nakamura
  • Organizer: 日本化学会第99春季年会
• [Presentation] Catalysis with Earth Abundant Transition Metals (2018)
  • Author(s): Laurean Ilies
  • Organizer: Asian Workshop of Experiment and Theory in Quantum Beam Molecular Sciences
  • Int'l Joint Research / Invited
• [Presentation] Iron-Catalyzed Oxidative Cross-Coupling of Thiophene Compounds with Carboxamides (2018)
  • Author(s): Takahiro Doba, Rui Shang, Tatsuaki Matsubara, Laurean Ilies, Eiichi Nakamura
  • Organizer: 結合切断化学と分子合成シンポジウム(第9回サブウェイセミナー)
• [Presentation] Iron-Catalyzed C-H Bond Activation (2018)
  • Author(s): Laurean Ilies
  • Organizer: The 4th International Symposium on C-H Activation (ISCHA-4)
  • Int'l Joint Research / Invited
• [Presentation] Iron-Catalyzed Oxidative Cross-Coupling of Thiophene Compounds with Carboxamides (2018)
  • Author(s): Takahiro Doba, Rui Shang, Tatsuaki Matsubara, Laurean Ilies, Eiichi Nakamura
  • Organizer: The 4th International Symposium on C-H Activation(国際学会)
  • Int'l Joint Research
• [Presentation] Iron-Catalyzed Oxidative Cross-Coupling of Thiophene Compounds with Carboxamides (2018)
  • Author(s): Takahiro Doba, Rui Shang, Tatsuaki Matsubara, Laurean Ilies, Eiichi Nakamura
  • Organizer: 第29回基礎有機化学討論会
• [Presentation] Iron-Catalyzed Oxidative Cross-Coupling of Thiophene Compounds with Carboxamides (2018)
  • Author(s): Takahiro Doba, Rui Shang, Tatsuaki Matsubara, Laurean Ilies, Eiichi Nakamura,
  • Organizer: 第65回有機金属化学討論会
• [Presentation] Iron-Mediated Carboamination and Carboalkoxylation of Alkenes (2018)
  • Author(s): Takumi Yoshida, Laurean Ilies, Eiichi Nakamura,
  • Organizer: 第65回有機金属化学討論会
• [Presentation] C-H活性化の鉄学 (2018)
  • Author(s): Laurean Ilies
  • Organizer: 第8回CSJ化学フェスタ，文科省科研費新学術領域研究「ハイブリッド触媒」特別企画:「1+1は3?」ハイブリッド触媒が紡ぎ出す新 反応化学
  • Invited
• [Presentation] C-H Activation with Base Metals (2018)
  • Author(s): Laurean Ilies
  • Organizer: The 13th International Conference on Cutting-Edge Organic Chemistry in Asia (ICCEOCA-13)
  • Int'l Joint Research / Invited
• [Book] C-H結合活性化反応 (2019)
  • Author(s): 日本化学会、イリエシュ ラウレアン、浅子 壮美、吉田 拓未
  • Total Pages: 128
  • Publisher: 共立出版
  • ISBN: 9784320044753
• [Remarks] 機能有機合成科学チームのオリジナルHP
  • URL: http://iliesteam.riken.jp/home_JP.html