Functionalization of aliphatic C-H bonds using hybrid organometallic/radical reactivity

• Project Area: Hybrid Catalysis for Enabling Molecular Synthesis on Demand
• Project/Area Number: 18H04643
• 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: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
• Keywords: organic synthesis / catalysis / 有機合成

Outline of Annual Research Achievements

The purpose of this project is the selective functionalization of C(sp3)-H bonds by exploiting a hybrid radical/organometallic reactivity of first row transition metals such as iron, manganese, cobalt, or nickel. We found that an iron salt and deprotonated carbazole form an amidoiron complex that in the presence of an aryl iodide and upon visible light irradiation aminates the alfa position of THF, or the allylic position of an alkene. While synthetically meaningful reaction scope and yield could not be achieved to date, these results demonstrate that the hybrid reactivity of first row transition metals can be initiated by light, instead of the previously used reactive Grignard reagents.
We also discovered a new reactivity of organomolybdenum species, which activated an aryl chloride or fluoride to promote a homocoupling or a cross-coupling reaction. These results are meaningful, because molybdenum is reluctant to react with aromatic halides, and molybdenum-catalyzed coupling of halides has been scarcely reported. We developed a molybdenum-catalyzed reaction of 2-haloaryl ketones, where two substrate molecules react in a cyclative manner to produce a phthalan derivative. The reaction scope and preliminary mechanistic studies were performed, and the manuscript is in preparation for publication.

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] 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] 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
  • 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
• [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