金属錯体反応場の精密構築に向けたキラル多座有機配位子の開発

• Project Area: Precise Formation of a Catalyst Having a Specified Field for Use in Extremely Difficult Substrate Conversion Reactions
• Project/Area Number: 16H01014
• 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: Nagoya University
• Principal Investigator: 北村 雅人 名古屋大学, 創薬科学研究科, 教授 (50169885)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 不斉水素化 / 多座配位子 / 光学活性配位子

Outline of Annual Research Achievements

sp3P/sp3NH/sp2N混合系の直線性3座配位子(R)-PN(H)NのRu錯体AはDMSOの存在下，キレート性・非キレート性を問わず立体的要請度の高いケトンを効率的に不斉水素化することができる，本研究では，構造的観点から反応機構の解明を目指した．ピリジン部sp2N原子を15N標識したPN(H)15N配位子とPh-PN(H)Nを用いて，本触媒反応に関連する錯体を合成し，15N-31P・1H-31Pの結合定数，PyC(6)H化学シフト，PyCHSHRNH部の結合型式，DMSOジメチル基の化学シフト差，nOeを指標にその詳細なNMR構造解析を実施した．Aはfac構造を有し．sp3P-trans dmso，sp2N-trans dmso，sp3N-trans dmsoの解離速度定数比は>50:1.7:1であることを明らかにした．AをCH3OH/DMSO中，2当量のt-BuOKで処理すると，定量的にメトキシヒドリド錯体Bが生成する．BはCH3OH中でのみ存在することができ，濃縮するとアミド錯体Cに移行する．BはCH3OH中，水素処理しても塩基の有無にかかわらずジヒドリド体Cは生成しない．ケトン基質が共存してはじめて触媒サイクルが回転する．THF中で1当量のt-BuOK存在下，Bを水素処理して、ジヒドリド錯体Dを得ることができた．塩基がないとDは生じない．sp3N-trans dmsoの酸素原子はPyC(6)Hと水素結合して空間配座が固定される．ここにキラルな環境が構築され高いエナンチオ選択性が発現する．これらのRu種の構造および生成条件は想定機構を強く支持する．全貌解明に向けて基盤となる重要な情報を得ることができた．

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Modular Construction of Protected 1,2/1,3-Diols, -Amino Alcohols, and -Diamines via Catalytic Asymmetric Dehydrative Allylation: An Application to Synthesis of Sphingosine (2017)
  • Author(s): Shinji Tanaka, Ramachandran Gunasekar, Tatsuya Tanaka, Yoko Iyoda, Yusuke Suzuki, and Masato Kitamura*
  • Journal Title: J. Org. Chem. Volume: 82 Issue: 17 Pages: 9160-9170
  • DOI: 10.1021/acs.joc.7b01181
  • Peer Reviewed
• [Journal Article] Synthetic analogs of an Entamoeba histolytica glycolipid designed to combat intracellular Leishmania infection. (2017)
  • Author(s): Choy, S.L.; Bernin, H.; Aiba, T.; Bifeld, E.; Lender, S.C.; Muhlenpfordt, M.; Noll, J.; Eick, J.; Marggraff, C.; Niss, H.; Roldan, N.G.; Tanaka, S.; Kitamura, M.; Fukase, K.; Clos, J.; Tannich, E.; Fujimoto, Y.; Lotter, H.
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 1-14
  • DOI: 10.1038/s41598-017-09894-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] π-Allyl Donicity Switch in Catalytic Asymmetric Allylation: Usability of a Robust and Feasible Allyl Methyl Ether (2017)
  • Author(s): Yusuke Suzuki ,Shoutaro Iwase ,Kazuki Hashimoto ,Shinji Tanaka , and Masato Kitamura
  • Journal Title: Chemistry Letters Volume: 46 Issue: 9 Pages: 1308-1310
  • DOI: 10.1246/cl.170533
  • NAID: 130006067862
  • ISSN: 0366-7022, 1348-0715
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis and biological evaluation of chemokine receptor ligands with 2-benzazepine scaffold (2017)
  • Author(s): Simone Thum, Artur K. Kokornaczyk, Tomoaki Seki, Monica De Maria, Natalia V. Ortiz Zacarias, Henk de Vries, Christina Weiss, Michael Koch, Dirk Schepmann, Masato Kitamura, Nuska Tschammer, Laura H. Heitman, Anna Junker, Bernhard Wuensch
  • Journal Title: European Journal of Medicinal Chemistry Volume: 135 Pages: 401-413
  • DOI: 10.1016/j.ejmech.2017.04.046
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Do GluN2B subunit containing NMDA receptors tolerate a fluorine atom in the phenylalkyl side chain? (2017)
  • Author(s): Yoshihiro Shuto, Simone Thum, Louisa Temme, Dirk Schepmann, Masato Kitamura and Bernhard Wuensch
  • Journal Title: MedChemComm Volume: 8 Issue: 5 Pages: 975-981
  • DOI: 10.1039/c6md00621c
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Enantio- and Diastereoselective Dehydrative “One-Step” Construction of Spirocarbocycles via a Ru/H+-Catalyzed Tsuji-Trost Approach (2017)
  • Author(s): Yusuke Suzuki, Namdev Vatmurge, Shinji Tanaka, Masato Kitamura
  • Journal Title: Chemistry - An Asian Journal Volume: 12 Issue: 6 Pages: 633-637
  • DOI: 10.1002/asia.201700013
  • Peer Reviewed
• [Journal Article] Development of an Axially Chiral sp3P/sp3NH/sp2N-Combined Linear Tridentate Ligand―fac-Selective Formation of Ru(II) Complexes and Application to Ketone Hydrogenation
 (2016)
  • Author(s): Tomoya Yamamura, Satoshi Nakane, Yuko Nomura, Shinji Tanaka, Masato Kitamura*
  • Journal Title: Tetrahedron Volume: 未定 Issue: 26 Pages: 3781-3789
  • DOI: 10.1016/j.tet.2016.02.007
  • Peer Reviewed
• [Journal Article] Development of a Divergent Synthetic Route to the Erythrina Alkaloids: Asymmetric Syntheses of 8-Oxo-erythrinine, Crystamidine, 8-Oxo-erythraline, and Erythraline (2016)
  • Author(s): Hirotatsu Umihara, Tomomi Yoshino, Jun Shimokawa, Masato Kitamura, Tohru Fukuyama
  • Journal Title: Angewandte Chemie International Edition Volume: 55 Issue: 24 Pages: 6915-6918
  • DOI: 10.1002/anie.201602650
  • Peer Reviewed
• [Journal Article] Enantioselective Total Synthesis of (+)-Hinckdentine A via a Catalytic Dearomatization Approach (2016)
  • Author(s): Kazuya Douki, Hiroyuki Ono, Tohru Taniguchi, Jun Shimokawa, Masato Kitamura, Tohru Fukuyama
  • Journal Title: Journal of the American Chemical Society Volume: 138 Issue: 44 Pages: 14578-14581
  • DOI: 10.1021/jacs.6b10237
  • Peer Reviewed
• [Presentation] Donor-Acceptor Bifunctional Catalyst―From DAIB–Zn to Ru/Brønsted Acid Combined Catalyst― (2018)
  • Author(s): 北村雅人
  • Organizer: International Congress on Pure&Applied Chemistry 2018
  • Int'l Joint Research / Invited
• [Presentation] ビスアミジン型２座配位子の開発と応用 (2017)
  • Author(s): 北村雅人
  • Organizer: 東北大学大学院薬学研究科有機化学セミナー
  • Invited
• [Presentation] 3.ビスアミジン型sp2N系二座配位子の開発 (2017)
  • Author(s): 北村雅人
  • Organizer: International Symposium on Pure & Applied Chemistry
  • Int'l Joint Research / Invited
• [Presentation] ビスアミジン型sp2N系二座配位子の開発 (2016)
  • Author(s): 北村雅人
  • Organizer: 講演会
  • Place of Presentation: 東京工業大学
  • Year and Date: 2016-12-19
  • Invited
• [Presentation] ヒンクデンチンAの不斉全合成 (2016)
  • Author(s): 道木和也、小野裕之、下川 淳、福山 透、北村雅人
  • Organizer: 第58回天然有機化合物討論会
  • Place of Presentation: 東北大学
  • Year and Date: 2016-09-14
• [Presentation] アリル化・脱アリル化―ルテニウム/ブレンステッド酸 混合触媒― (2016)
  • Author(s): 北村雅人
  • Organizer: 講演会「有機金属化学の大潮流」
  • Place of Presentation: 分子科学研究所
  • Year and Date: 2016-09-02
  • Invited