窒素固定化プロセスを含む新規炭素―水素結合の直接的アミノ化反応の開発

• Project Area: Molecule Activation Directed toward Straightforward Synthesis
• Project/Area Number: 23105501
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Hokkaido University
• Principal Investigator: 佐藤 美洋 北海道大学, 薬学研究科(研究院), 教授 (90226019)
• Project Period (FY): 2011-04-01 – 2013-03-31
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2011: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: C-H結合活性化 / 不活性結合 / 分子活性化 / 窒素固定 / C-N結合 / アミノ化反応 / 触媒・化学プロセス / 合成化学

Outline of Annual Research Achievements

生物活性化合物の多くは窒素原子を含み，窒素原子の存在が機能の発現に関係することから，炭素―窒素結合形成反応の開発も有機合成化学においては非常に重要である．本研究課題では，申請者らが以前見出したチタン化合物を用いた「窒素固定化反応」を，遷移金属触媒による「C-H結合活性化法」と組み合わせることにより「C-H結合の活性化」を伴う「窒素固定化反応」の開発を目指し検討を行なった．今年度の検討結果において，これまでに報告されているPd, Cu, Auなどの金属錯体による「C-H結合活性化法」と，申請者らの開発したチタン化合物を用いた「窒素固定化反応」によって生成する「チタンー窒素錯体混合物（Ti-N錯体）」とを組み合わせ種々検討したが，目的の達成は困難であった．そこでより研究の根源に立ち返り，１）新たな「C-H結合の活性化」の開発，及び２）新たな「窒素固定化反応」の開発，に焦点を絞り研究を行った．その結果，新たな「C-H結合の活性化」法として，「Rh触媒を用いたメタラサイクルの形成をきっかけとするC(sp3)-H結合活性化法の開発」及び「Ir触媒を用いたC(sp3)-H結合のシリル化を経由する直接的カルボキシル化」の二つの新規反応を開発することができた．一方，新たな「窒素固定化反応」に関して，Ti錯体と同族のZr錯体がTiと同等以上の「窒素固定化能」を持つことを見出しすことができた．Zi(IV)錯体はTi(IV)錯体よりもルイス酸性が低いため空気中で取り扱いやすく、またより穏やかな条件で窒素固定化反応が進むこと，及び同族ではあるがTiより後周期に属するZrの方が他の金属試薬とのトランスメタル化能力が高い可能性もあり，その性質に大変興味が持たれる．

Research Progress Status

24年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

24年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] One-Step Synthesis of Racemic α-Amino Acids from Aldehydes, Amine Components, and Gaseous CO2 by the Aid of a Bismetal Reagent (2013)
  • Author(s): Tsuyoshi Mita, Yuki Higuchi, and Yoshihiro Sato
  • Journal Title: Chem. Eur. J. Volume: 19 Issue: 3 Pages: 1123-1128
  • DOI: 10.1002/chem.201202332
  • Peer Reviewed
• [Journal Article] Addition of Cyclic Ureas and 1-Methyl-2-oxazolidone to Pyridynes: A New Approach to Pyridodiazepines, Pyridodiazocines, and Pyridooxazepines (2013)
  • Author(s): Nozomi Saito, Ken-ichi Nakamura, Sayako Shibano, Soichiro Ide, Masabumi Minami, and Yoshihiro Sato
  • Journal Title: Org. Lett. Volume: 15 Issue: 2 Pages: 386-389
  • DOI: 10.1021/ol303352q
  • Peer Reviewed
• [Journal Article] Regio- and Stereoselective Synthesis of Tri- and Tetrasubstituted Enamides via Palladium-Catalyzed Silaboration of Ynamides (2013)
  • Author(s): Nozomi Saito, Keiichi Saito, Hiroyasu Sato, and Yoshihiro Sato
  • Journal Title: Adv. Synth. Catal. Volume: 355 Issue: 5 Pages: 853-856
  • DOI: 10.1002/adsc.201201111
  • Peer Reviewed
• [Journal Article] Convenient and Practical Synthesis ofα-Amido Stannanes (2012)
  • Author(s): Mita, T.; Higuchi, Y.; Sato. Y.
  • Journal Title: Synthesis Volume: 44 Issue: 02 Pages: 194-200
  • DOI: 10.1055/s-0031-1289597
  • Peer Reviewed
• [Journal Article] Nicekel-Catatalyzed Enantion- and Diastereoselective Three-Component Coupling of 1,3-Diene, Aldehyde, and Silylborane Leading to an α-Chiral (2012)
  • Author(s): Nozomi Saito
  • Journal Title: Angew.Chem.Int.Ed. Volume: 51 Issue: 5 Pages: 1228-1231
  • DOI: 10.1002/anie.201107360
  • Peer Reviewed
• [Journal Article] Synthesis of Arylglycine and Mandelic Acid Derivatives through Carboxylations ofα-Amido andα-Acetoxy Stannanes with Carbon Dioxide (2012)
  • Author(s): Mita, T.; Sugawara, M.; Hasegawa, H.; Sato, Y.
  • Journal Title: J. Org. Chem. Volume: 77 Issue: 5 Pages: 2159-2168
  • DOI: 10.1021/jo202597p
  • Peer Reviewed
• [Journal Article] Synthesis of 1,2-Bisalkylidenecyclopentanes from 1,6-Allenynes via Stereoselective Addition of Nucleophiles to Ruthenacyclopentenes (2012)
  • Author(s): Nozomi Saito
  • Journal Title: Chem.Commum. Volume: 48 Issue: 31 Pages: 3754-3756
  • DOI: 10.1039/c2cc30640a
  • Peer Reviewed
• [Journal Article] Total Synthesis of (-)-Herbindoles A, B, and C via Transition Metal-Catalyzed Intramolecular [2+2+2] Cyclization between Ynamide and Diynes (2012)
  • Author(s): Nozomi Saito
  • Journal Title: Org.Lett. Volume: 14 Issue: 7 Pages: 1914-1917
  • DOI: 10.1021/ol300571b
  • Peer Reviewed
• [Journal Article] Ruthenium-Catalyzed Intramolecular [2+2+2] cyclization of Allene-Yne-Enes : Construction of Fused-Tricyclic Skeletons (2012)
  • Author(s): Nozomi Saito
  • Journal Title: Chem.Asian J. Volume: 7(印刷中) Issue: 7 Pages: 1521-1523
  • DOI: 10.1002/asia.201200201
  • Peer Reviewed
• [Journal Article] Csp3-H Bond Activation Triggered by Formation of Metallacycles: RhI-Catalyzed Cyclopropanation/Cyclization of Allenynes (2012)
  • Author(s): Yoshihiro Oonishi, Yoshitaka Kitano and Yoshihiro Sato
  • Journal Title: Angew. Chem. Int. Ed. Volume: 51 Issue: 29 Pages: 7305-7308
  • DOI: 10.1002/anie.201203772
  • Peer Reviewed
• [Journal Article] Sequential Protocol for C(sp3)-H Carboxylation with CO2: Transition Metal-Catalyzed Benzylic C-H Silylation and Fluoride-Mediated Carboxylation (2012)
  • Author(s): Tsuyoshi Mita, Kenichi Michigami, and Yoshihiro Sato
  • Journal Title: Org. Lett. Volume: 14 Issue: 13 Pages: 3462-3465
  • DOI: 10.1021/ol301431d
  • Peer Reviewed
• [Journal Article] Construction of Eight-Membered Rings : Intermolecular Rhodium-Catalyzed [6+2] Cycloaddition of 4-Allenals with Alkynes (2012)
  • Author(s): Yoshihiro Oonishi, Akihito Hosotani, Yoshihiro Sato
  • Journal Title: Angewandte Chemie International Edition Volume: 51 Issue: 46 Pages: 11548-11551
  • DOI: 10.1002/anie.201206508
  • Peer Reviewed
• [Journal Article] One-Pot Synthesis of α-Amino Acids from CO_2 Using a Bismetal Reagent with Si-B Bond (2012)
  • Author(s): ita, Jianyang Chen, Masumi Sugawara, Yo
  • Journal Title: Organic Lettes Volume: 14 Issue: 24 Pages: 6202-6205
  • DOI: 10.1021/ol302952r
  • Peer Reviewed
• [Journal Article] Ruthenium-Catalyzed Cyclization of Enynes via a Ruthenacyclopentene Intermediate-Development of Three Novel Cyclizations Controlled by a Substituent on Alkyne of Enyne- (2011)
  • Author(s): Nozomi Saito
  • Journal Title: Chem.Rec. Volume: 11 Issue: 4 Pages: 186-198
  • DOI: 10.1002/tcr.201100003
  • Peer Reviewed
• [Journal Article] Rh(I)-Catalyzed Formal [6+2] Cycloaddition of 4-Allenals with Alkynes or Alkenes in a Tether (2011)
  • Author(s): Yoshihiro, Oonishi
  • Journal Title: Journal of the American Chemical Society Volume: 133 Issue: 27 Pages: 10-386
  • DOI: 10.1021/ja203824v
  • Peer Reviewed
• [Journal Article] Regio- and Stereoselective Synthesis of 2-Amino-1,3-Diene Derivatives by Ruthenium-Catalyzed Coupling of Ynamides and Ethylene (2011)
  • Author(s): Nozomi Saito
  • Journal Title: Org.Lett Volume: 13 Issue: 10 Pages: 2718-2721
  • DOI: 10.1021/ol200812y
  • Peer Reviewed
• [Journal Article] Practical Synthesis of N-Boc-and N-Cbz-α-Amido Stannanes fromα-Amido Sulfones Using TMSSnBu3 and CsF (2011)
  • Author(s): Mita, T.; Higuchi, Y.; Sato. Y.
  • Journal Title: Org. Lett. Volume: 13 Issue: 9 Pages: 2354-2357
  • DOI: 10.1021/ol200599d
  • Peer Reviewed
• [Journal Article] Nickel-Promoted Carboxylation/Cyclization Cascade of Allenyl Aldehyde Under an Atmosphere of CO2 (2011)
  • Author(s): Masanori Takimoto
  • Journal Title: Synlett Volume: 0 Issue: 10 Pages: 1423-1426
  • DOI: 10.1055/s-0030-1260565
  • Peer Reviewed
• [Journal Article] Total Synthesis of(-)-Corynantheidine by Nickel-Catalyzed Carboxylative Cyclization of Enynes (2011)
  • Author(s): Takashi Mizuno, Yoshihiro Oonishi, Masanori Takimoto, and Yoshihiro Sato
  • Journal Title: Eur. J. Org. Chem. Volume: 0 Issue: 14 Pages: 2606-2609
  • DOI: 10.1002/ejoc.201100147
  • Peer Reviewed
• [Journal Article] One-Pot Synthesis ofα-Amino Acids from Imines through CO_2 Incorporation : An Alternative Method for Strecker Synthesis (2011)
  • Author(s): Mita, T.; Chen, J.; Sugawara, M.; Sato, Y.
  • Journal Title: Angew. Chem., Int. Ed. Volume: 50 Issue: 6 Pages: 1393-1396
  • DOI: 10.1002/anie.201006422
  • Peer Reviewed
• [Journal Article] Asymmetric Synthesis of γ-Siloxyenamides via Chiral Auxiliary-Mediated Diastereoselectivre Coupling of Ynamides, Aldehydes, and Silane by Nickel Catalyst (2011)
  • Author(s): Nozomi Saito
  • Journal Title: Heterocycles Volume: 82 Issue: 2 Pages: 1181-1187
  • DOI: 10.3987/com-10-s(e)122
  • Peer Reviewed
• [Presentation] Rhodium-Catalyzed Cyclizations between Allene, Aldehdye, and Alkyne (2012)
  • Author(s): 佐藤美洋
  • Organizer: Cambodian Malaysian Chemical Conference (CMCC)
  • Place of Presentation: Angkor Century Resort Spa（カンボジア）
  • Year and Date: 2012-10-17
  • Invited
• [Presentation] Rh(I)-Catalyzed [6+2] Cycloaddition of 4-Allenals with Alkynes (2012)
  • Author(s): 細谷昭仁
  • Organizer: 第59回有機金属化学討論会
  • Place of Presentation: 大阪大学（大阪市）
  • Year and Date: 2012-09-13
• [Presentation] Rh(I)触媒によるアレンインとアルデヒドの[2+2+2]環化反応：ピラン環を含む多環式骨格の新規構築法の開発 (2012)
  • Author(s): 北野喜隆
  • Organizer: 第59回有機金属化学討論会
  • Place of Presentation: 大阪大学（大阪市）
  • Year and Date: 2012-09-13
• [Presentation] RHODIUM-CATALYZED CYCLOPROPANATIVE CYCLIZATION OF ALLENYNES (2012)
  • Author(s): 佐藤美洋
  • Organizer: ICOMC-25
  • Place of Presentation: リスボン大学（ポルトガル）
  • Year and Date: 2012-09-02
• [Presentation] RHODIUM-CATALYZED CYCLIZATION OF ALLENEYNES WITH ALDEHYDE: EASY ACCESS TO BICYCLO[5.3.0]DECATRIENE SKELETON (2012)
  • Author(s): 横江貴之
  • Organizer: ICOMC-25
  • Place of Presentation: リスボン大学（ポルトガル）
  • Year and Date: 2012-09-02
• [Presentation] SEQENTIAL PROTOCOL FOR C(sp3)-H CARBOXYLATION WITH CO2: TRANSITION METAL-CATALYZED BENZYLIC C-H SILYLATION AND FLUORIDE-MEDIATED CARBOXYLATION (2012)
  • Author(s): 道上憲一
  • Organizer: ICOMC-25
  • Place of Presentation: リスボン大学（ポルトガル）
  • Year and Date: 2012-09-02
• [Presentation] Rh(I)-Catalyzed Cyclizations of Allenyl Aldehydes (2011)
  • Author(s): 佐藤美洋
  • Organizer: 第14回アジア化学会議(14ACC)
  • Place of Presentation: クイーンシリキットナショナルコンベンションセンター(タイ)(招待講演)
  • Year and Date: 2011-09-08