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2013 年度 実績報告書

Iron-Catalyzed C(sp3)-H Bond Functionalization

公募研究

研究領域直截的物質変換をめざした分子活性化法の開発
研究課題/領域番号 25105711
研究種目

新学術領域研究(研究領域提案型)

研究機関東京大学

研究代表者

イリエシュ ラウレアン  東京大学, 理学(系)研究科(研究院), 助教 (40569951)

研究期間 (年度) 2013-04-01 – 2015-03-31
キーワードiron / C-H activation
研究概要

Aliphatic hydrocarbons containing various functional groups are ubiquitous in nature and therefore are important synthetic targets. The purpose of this project is the development of synthetic methods to functionalize aliphatic hydrocarbons in a straightforward and step-efficient manner through C-H bond activation, using cheap, abundant, and non-toxic iron as a catalyst under mild reaction conditions.
During FY2013, I have developed an iron-catalyzed reaction of propionamides with organozinc reagents. By contrast to previous reports that used precious transitions metals as the catalyst, the present reaction proceeds under mild reaction conditions and with the tolerance of functional groups such as chloride and bromide. The reaction proceeds regioselectively to give a beta-arylated propionamide with high yield. The obtained compounds can be hydrolysed to the corresponding aliphatic carboxylic acids, compounds of importance for medicinal chemistry and industry.
From a scientific point of view, this work offers insights into the key parameters that govern the activation of a C-H bond with organoiron species. Thus, a bidentate group and a diphoshine ligand are required to stabilise the active iron species, and the appropriate positioning of the C-H bond with respect to the directing group is required in order for the C-H cleavage to proceed smoothly.

現在までの達成度 (区分)
現在までの達成度 (区分)

1: 当初の計画以上に進展している

理由

The reaction developed in FY2013 is the first iron-catalyzed sp3 C-H activation reported to date. This work demonstrates that iron, which is of interest for environmental and economical reasons, can rival and even surpass precious metals such as palladium in terms of efficiency, selectivity, and mildness of the reaction conditions. This work was published in the top journal for chemistry (Journal of the American Chemical Society) and presented at various national and international conferences. The mechanistic insights into the factors governing the reactivity of iron was further exploited for the development of several related reactions such as the iron-catalyzed allylation and amination through C-H bond activation; these reactions have both been recently published in the Journal of the American Chemical Society.

今後の研究の推進方策

While the reaction developed in FY2013 is a pioneering example of iron-catalyzed aliphatic C-H bond activation, this reaction has several drawbacks. For example: 1) a large amount of organozinc reagents, which are sensitive to moisture and air, expensive, and difficult to handle, must be used used as the arylating reagent; 2) the scope of the amide substrate is narrow; 3) the narrow substrate scope together with limitations in the repertoire of the ligand hampered the development of an asymmetric version of this reaction.
In FY 2014, I plan to address these problems through the use of organoboron reagents. Organoborons are commercially available, stable and easy to handle, and functional group tolerant. Moreover, they have lower reducing ability than the organozinc reagents, and therefore it is expected they will not reduce iron to a low-valent species which is difficult to control, resulting in narrow reaction scope.
However, transmetallation of iron with organoboron reagents is difficult. I envision that the use of an appropriate additive may enhance the problematic transmetallation process, and preliminary results showed that a zinc(II) salt may be effective. Based on this initial result, I plan to develop a broad and general reaction of aliphatic amides with organoboron reagents, including aryl, alkenyl, and alkyl reagents. Next, development of chiral ligands for iron will be conduced to achieve iron-catalyzed enantioselective C-H bond activation. These reactions can be of potential use for the synthesis of target molecules for medicinal chemistry.

  • 研究成果

    (22件)

すべて 2014 2013

すべて 雑誌論文 (4件) (うち査読あり 4件) 学会発表 (16件) (うち招待講演 3件) 図書 (1件) 産業財産権 (1件)

  • [雑誌論文] Synthesis of Anthranilic Acid Derivatives through Iron-Catalyzed Ortho Amination of Aromatic Carboxamides with N-Chloroamines2014

    • 著者名/発表者名
      Tatsuaki Matsubara, Sobi Asako, Laurean Ilies, Eiichi Nakamura
    • 雑誌名

      Journal of the American Chemical Society

      巻: 136 ページ: 646-649

    • DOI

      10.1021/ja412521k

    • 査読あり
  • [雑誌論文] Synthesis of Polysubstituted Enynes via Iron-Catalyzed Carbomagnesiation of Conjugated Diynes2014

    • 著者名/発表者名
      Laurean Ilies, Takumi Yoshida, Eiichi Nakamura
    • 雑誌名

      Synlett

      巻: 25 ページ: 527-530

    • DOI

      10.1055/s-0033-1340476

    • 査読あり
  • [雑誌論文] β-Arylation of Carboxamides via Iron-Catalyzed C(sp3)-H Bond Activation2013

    • 著者名/発表者名
      Rui Shang, Arimasa Matsumoto, Laurean Ilies, Eiichi Nakamura
    • 雑誌名

      Journal of the American Chemical Society

      巻: 135 ページ: 6030-6032

    • DOI

      10.1021/ja402806f

    • 査読あり
  • [雑誌論文] Iron-Catalyzed Ortho Allylation of Aromatic Carboxamides with Allyl Ethers2013

    • 著者名/発表者名
      Sobi Asako, Laurean Ilies, Eiichi Nakamura
    • 雑誌名

      Journal of the American Chemical Society

      巻: 135 ページ: 17755-17757

    • DOI

      10.1021/ja4106368

    • 査読あり
  • [学会発表] Iron-Catalyzed Directed Coupling of C(sp2)-H Bond with Organoboron Compounds2014

    • 著者名/発表者名
      Rui Shang, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      The 94th Spring Meeting of the Chemical Society of Japan
    • 発表場所
      名古屋大学(名古屋県)
    • 年月日
      20140327-20140330
  • [学会発表] Iron-Catalyzed ortho Alkylation of Aromatic Carboxamides with Alkylzinc Reagents2014

    • 著者名/発表者名
      Saki Ichikawa, Sobi Asako, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      The 94th Spring Meeting of the Chemical Society of Japan
    • 発表場所
      名古屋大学(名古屋県)
    • 年月日
      20140327-20140330
  • [学会発表] Iron-Catalyzed C-H Functionalization2013

    • 著者名/発表者名
      Laurean Ilies
    • 学会等名
      The 41th Organometallic Seminar “Frontiers of Catalysis”
    • 発表場所
      岡山大学(岡山県)
    • 年月日
      20131219-20131219
    • 招待講演
  • [学会発表] Iron-Catalyzed C-H Activation2013

    • 著者名/発表者名
      Laurean Ilies, Eiichi Nakamura
    • 学会等名
      International Symposium on Catalysis and Fine Chemicals
    • 発表場所
      Renmin University, Beijing
    • 年月日
      20131201-20131205
    • 招待講演
  • [学会発表] Synthesis of Polysubstituted-Enynes via Iron-Catalyzed Carbomagnesiation of Conjugated Diynes2013

    • 著者名/発表者名
      Takumi Yoshida, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      International Symposium on Catalysis and Fine Chemicals
    • 発表場所
      Renmin University, Beijing
    • 年月日
      20131201-20131205
  • [学会発表] Iron-Catalyzed ortho Amination of Aromatic Carboxamides2013

    • 著者名/発表者名
      Tatsuaki Matsubara, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      International Symposium on Catalysis and Fine Chemicals
    • 発表場所
      Renmin University, Beijing
    • 年月日
      20131201-20131205
  • [学会発表] Iron-Catalyzed Directed C-H Bond Allylation of Arenes2013

    • 著者名/発表者名
      Sobi Asako, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      International Symposium on Catalysis and Fine Chemicals
    • 発表場所
      Renmin University, Beijing
    • 年月日
      20131201-20131205
  • [学会発表] Iron-Catalyzed 8-Quinolineamide-Directed C(sp3)-H Bond Arylation2013

    • 著者名/発表者名
      Rui Shang, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      International Symposium on Catalysis and Fine Chemicals
    • 発表場所
      Renmin University, Beijing
    • 年月日
      20131201-20131205
  • [学会発表] Iron-Catalyzed Directed C-H Activation2013

    • 著者名/発表者名
      Laurean Ilies
    • 学会等名
      The 4th Symposium for Young Chemists on Molecular Activation
    • 発表場所
      KKR鹿児島敬天閣(鹿児島県)
    • 年月日
      20131114-20131115
    • 招待講演
  • [学会発表] Iron-Catalyzed Directed Amination of C(sp2)-H Bonds2013

    • 著者名/発表者名
      Tatsuaki Matsubara, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      The 3rd CSJ Chemistry Festa
    • 発表場所
      タワーホール船堀(東京都)
    • 年月日
      20131021-20131023
  • [学会発表] Iron-Catalyzed γ-Selective Allylation of Aromatic C-H Bond2013

    • 著者名/発表者名
      Sobi Asako, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      The 3rd CSJ Chemistry Festa
    • 発表場所
      タワーホール船堀(東京都)
    • 年月日
      20131021-20131023
  • [学会発表] Iron-Catalyzed C-H Bond Activation using Bidentate Directing Group2013

    • 著者名/発表者名
      Laurean Ilies, Sobi Asako, Rui Shang, Tatsuaki Matsubara, Arimasa Matsumoto, Eiichi Nakamura
    • 学会等名
      The 60th Symposium on Organometallic Chemistry
    • 発表場所
      学習院大学(東京都)
    • 年月日
      20130912-20130914
  • [学会発表] Iron-Catalyzed Directed Amination of C(sp2)-H Bonds2013

    • 著者名/発表者名
      Tatsuaki Matsubara, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      The 60th Symposium on Organometallic Chemistry
    • 発表場所
      学習院大学(東京都)
    • 年月日
      20130912-20130914
  • [学会発表] Iron-Catalyzed Allylation via Aromatic C-H Bond Activation2013

    • 著者名/発表者名
      Sobi Asako, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      The 17th IUPAC International Symposium on Organometallic Chemistry Directed Towards Organic Synthesis
    • 発表場所
      Fort Collins, Colorado
    • 年月日
      20130728-20130801
  • [学会発表] Iron-Catalyzed Allylation via Aromatic C-H Bond Activation2013

    • 著者名/発表者名
      Sobi Asako, Laurean Ilies, Eiichi Nakamura
    • 学会等名
      The Third International Symposium on Molecular Activation
    • 発表場所
      Steamboat Springs, Colorado
    • 年月日
      20130726-20130728
  • [学会発表] Iron-Catalyzed C(sp3)-H Bond Activation for Arylation of Aliphatic Carboxamides2013

    • 著者名/発表者名
      Laurean Ilies
    • 学会等名
      The First Asian Conference for “MONODUKURI” Strategy by Synthetic Organic Chemistry
    • 発表場所
      サザンビーチホテル&リゾート沖縄(沖縄県)
    • 年月日
      20130717-20130719
  • [図書] The Chemistry of Organoiron Compounds2014

    • 著者名/発表者名
      Laurean Ilies, Eiichi Nakamura
    • 総ページ数
      28
    • 出版者
      John Wiley&Sons, Ltd
  • [産業財産権] 特許2014

    • 発明者名
      中村栄一,イリエシュ ラウレアン,尚睿
    • 権利者名
      東京大学
    • 産業財産権種類
      特許
    • 産業財産権番号
      2014-047532
    • 出願年月日
      2014-03-11

URL: 

公開日: 2015-05-28  

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