新規光学活性チオラート配位子をもつ金属触媒の開発と不斉還元的アミノ化反応への応用

• Project/Area Number: 17F17415
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 外国
• Research Field: Chemical pharmacy
• 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)
• Co-Investigator(Kenkyū-buntansha): MANNA SUDIPTA 名古屋大学, 創薬科学研究科, 外国人特別研究員
• Project Period (FY): 2017-11-10 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥2,200,000 (Direct Cost: ¥2,200,000); Fiscal Year 2019: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2018: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2017: ¥500,000 (Direct Cost: ¥500,000)
• Keywords: チオラート錯体 / 不斉合成 / チオラート

Outline of Annual Research Achievements

研究では、新しい触媒の探索によって、これまで困難とされてきた、水素分子によるケトンのエナンチオ還元的アミノ化反応の確立を目指す。その触媒候補として、チオールないしその共役アニオンであるチオラートを配位子としてもつ遷移金属錯体に着目した。SH基の高い酸性度により、カ ルボニル存在下でのイミノ基の選択的活性化が可能となるだけでなく、強い金属との親和性により、生成物であるアミンの過剰配 位による触媒の失活の心配もない。二つのチオール基をビナフチルに導入したBINAS誘導体、チオナフトール基をもつインデン配位子INDENASを具体的な標的錯体に定め、光学活性配位子の合成、遷移金属錯体形成の検証、α-ケト酸からのアミノ酸合成を標 的反応として反応性調査を進めた。これまでに、INDENAS配位子の合成法を検討した結果、2-メチルインダノンと2-メルカプトナフタレン-1-ブロマイドから合成する経路を確立してきた。インデニル基の2位には メチル基の他にtert-ブチル基も導入できる。光学分割法も確立した。これらの配位子を用いて、還元能力に定評のあるイリジウム、ロジウム、ルテニウム錯体を 合成し、その一部において結晶中での分子構造を明らかとすることができた。これらと、BINAS錯体との触媒を用いて、ベンゾイルギ酸の還元的アミノ化反応を検討したところ、定量的に反応が進行し、程度は低いながらもエナンチオ選択性も発現することを明らかとした。今後、触媒構造の最適化、条件検討を進め、新しいアミノ酸合成法を確立する。

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] CpRuII-chiral bisamidine complex catalyzed asymmetric Carroll-type decarboxylative allylation of β-keto allyl esters (2020)
  • Author(s): Ogawa Shintarou、Miyata Kengo、Kawakami Sho、Tanaka Shinji、Kitamura Masato
  • Journal Title: Tetrahedron Volume: 76 Issue: 7 Pages: 130888-130888
  • DOI: 10.1016/j.tet.2019.130888
  • Peer Reviewed
• [Journal Article] CpRu/Bronsted Acid-Catalyzed Enantioselective Dehydrative Cyclization of Pyrroles N-Tethered with Allylic Alcohols (2020)
  • Author(s): Iwase Shoutaro、Suzuki Yusuke、Tanaka Shinji、Kitamura Masato
  • Journal Title: Organic Letters Volume: 22 Issue: 5 Pages: 1929-1933
  • DOI: 10.1021/acs.orglett.0c00290
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Chiral Picolinic Acid Ligand, Cl-Naph-PyCOOH, for CpRu-Catalyzed Dehydrative Allylation: Design, Synthesis, and Properties (2019)
  • Author(s): Tanaka Shinji、Suzuki Yusuke、Kimura Takahiro、Kitamura Masato
  • Journal Title: Bulletin of the Chemical Society of Japan Volume: 92 Issue: 10 Pages: 1707-1720
  • DOI: 10.1246/bcsj.20190134
  • NAID: 130007728635
  • Peer Reviewed / Open Access
• [Journal Article] Water, an Essential Element for a ZnII‐Catalyzed Asymmetric Quinone Diels‐Alder Reaction: Multi‐Selective Construction of Highly Functionalized cis‐Decalins (2019)
  • Author(s): Morimoto Kyosuke、Le Thien Phuc、Manna Sudipta Kumar、Kiran I. N. Chaithanya、Tanaka Shinji、Kitamura Masato
  • Journal Title: Chemistry - An Asian Journal Volume: 14 Issue: 19 Pages: 3283-3290
  • DOI: 10.1002/asia.201900995
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis of the core structure of phalarine (2019)
  • Author(s): Douki Kazuya、Shimokawa Jun、Kitamura Masato
  • Journal Title: Organic & Biomolecular Chemistry Volume: 17 Issue: 7 Pages: 1727-1730
  • DOI: 10.1039/c8ob02320d
  • Peer Reviewed
• [Journal Article] Short and Atom-Economic Enantioselective Synthesis of the σ1-Receptor Ligands (S)- and (R)-Fluspidine-Important Tools for Positron Emission Tomography Studies (2019)
  • Author(s): Bunse Paul、Schlepphorst Christoph、Glorius Frank、Kitamura Masato、W?nsch Bernhard
  • Journal Title: The Journal of Organic Chemistry Volume: 84 Issue: 21 Pages: 13744-13754
  • DOI: 10.1021/acs.joc.9b01882
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rapid Entry into Biologically Relevant α,α-Difluoroalkylphosphonates Bearing Allyl Protection-Deblocking under Ru(II)/(IV)-Catalysis (2019)
  • Author(s): Panigrahi Kaushik、Fei Xiang、Kitamura Masato、Berkowitz David B.
  • Journal Title: Organic Letters Volume: 21 Issue: 24 Pages: 9846-9851
  • DOI: 10.1021/acs.orglett.9b03707
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Bisamidine-Cu(I)-catalyzed C-Allylation of 1,3-Dicarbonyl Compounds with Simple Cyclic Alkenes Using Di-tert-butyl Peroxide (2018)
  • Author(s): Tanaka Shinji、Ramachandran Gunasekar、Hori Yohei、Kitamura Masato
  • Journal Title: Chemistry Letters Volume: 47 Issue: 12 Pages: 1486-1489
  • DOI: 10.1246/cl.180741
  • NAID: 130007534810
  • Peer Reviewed / Open Access
• [Journal Article] Revisiting the CuII-Catalyzed Asymmetric Friedel-Crafts Reaction of Indole with Trifluoropyruvate (2018)
  • Author(s): Le Thien Phuc、Higashita Kazuyuki、Tanaka Shinji、Yoshimura Masahiro、Kitamura Masato
  • Journal Title: Organic Letters Volume: 20 Issue: 22 Pages: 7149-7153
  • DOI: 10.1021/acs.orglett.8b03086
  • Peer Reviewed
• [Journal Article] Mechanistic Study of the Ru-Catalyzed Asymmetric Hydrogenation of Nonchelatable and Chelatable tert-Alkyl Ketones Using the Linear Tridentate sp3P/sp3NH/sp2N-Combined Ligand PN(H)N: RuNH- and RuNK-Involved Dual Catalytic Cycle (2018)
  • Author(s): Nakane Satoshi、Yamamura Tomoya、Manna Sudipta Kumar、Tanaka Shinji、Kitamura Masato
  • Journal Title: ACS Catalysis Volume: 8 Issue: 12 Pages: 11059-11075
  • DOI: 10.1021/acscatal.8b02671
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Synthesis of fluspidine via asymmetric NaBH4 reduction of silicon enolates of β-keto esters (2018)
  • Author(s): Nakane Satoshi、Yoshinaka Sho、Iwase Shoutaro、Shuto Yoshihiro、Bunse Paul、Wuensch Bernhard、Tanaka Shinji、Kitamura Masato
  • Journal Title: Tetrahedron Volume: 74 Issue: 38 Pages: 5069-5084
  • DOI: 10.1016/j.tet.2018.04.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
• [Presentation] Mechanistic Study on Intramolecular Asymmetric Dehydrative Allylation of Alcohols Catalyzed by CpRu Complex of Chiral 2-Pyridinecarboxylic Acid Ligand (2019)
  • Author(s): 田中慎二, 鈴木悠介, 岩瀬翔太郎, 北村雅人
  • Organizer: 20th Tetrahedron Symposium
  • Int'l Joint Research
• [Presentation] CpRu-catalyzed Enantioselective Dehydrative Cyclization of Protic Nucleophile tethered Allylic Alcohols -From Allyl Protecting Group Chemistry to Tsuji-Trost-type Allylation- (2019)
  • Author(s): 北村雅人
  • Organizer: 27th International Society of Heterocyclic Chemistry Congress
  • Int'l Joint Research / Invited
• [Presentation] Mechanistic Insight into fac-PN(H)N-Ru Catalyzed Asymmetric Hydrogenation of tert-Alkyl Ketones (2019)
  • Author(s): 中根智志, 田中慎二, 北村雅人
  • Organizer: 第66回有機金属化学討論会
• [Presentation] 辻-トロスト反応の新展開 (2019)
  • Author(s): 北村雅人
  • Organizer: 岡山大学大学院自然科学研究科講演会
  • Invited
• [Presentation] 辻-トロスト反応の新展開 (2019)
  • Author(s): 北村雅人
  • Organizer: 北海道大学大学院工学研究院講演会
  • Invited
• [Presentation] 環境負荷低減型「触媒的不斉辻・トロスト反応」の開発に向けて (2019)
  • Author(s): 北村雅人
  • Organizer: 第2回グリーン合成&触媒 名古屋シンポジウム
  • Invited
• [Presentation] 脱水型触媒的不斉 Tsuji-Trost 反応の機構解明研究 (2019)
  • Author(s): 北村雅人
  • Organizer: 新学術領域研究「精密制御反応場」 第6回公開シンポジウム
  • Invited
• [Presentation] Dehydrative Tsuji-Trost-type Allylation Using CpRu/Broensted Acid Combined Catalyst: Mechanism (2019)
  • Author(s): 北村雅人
  • Organizer: The 8th Kansai-CMDS Meeting on OMCOS at Seoul
  • Int'l Joint Research / Invited
• [Presentation] PNN-Ru-DMSO錯体を触媒に用いるケトン類の不斉水素化の機構 (2018)
  • Author(s): 北村雅人
  • Organizer: 新学術領域研究「精密制御反応場」 第4回公開シンポジウム
  • Invited
• [Presentation] Donor-Acceptor Bifunctional Catalyst ―From DAIB-Zn to Ru/Broensted Acid Combined Catalyst― (2018)
  • Author(s): 北村雅人
  • Organizer: International Symposium on Pure&Applied Chemistry 2018
  • Int'l Joint Research / Invited
• [Presentation] ドナー・アクセプター二官能性触媒の開発 (2018)
  • Author(s): 北村雅人
  • Organizer: 京都大学大学院理学研究科有機合成化学研究室 大学院講義
  • Invited
• [Presentation] Chemistry In JAPAN (2018)
  • Author(s): 北村雅人
  • Organizer: Islom Karimov Nomidagi Toshkent Davlat Texnika Universiteti
  • Int'l Joint Research / Invited
• [Presentation] Donor-Acceptor Bifunctional Catalyst ―From DAIB-Zn to Ru/Broensted Acid Combined Catalyst― (2018)
  • Author(s): 北村雅人
  • Organizer: Bristol-Myers Squibb講演会
  • Int'l Joint Research / Invited
• [Presentation] Donor-Acceptor Bifunctional Catalyst ―From DAIB-Zn to Ru/Broensted Acid Combined Catalyst― (2018)
  • Author(s): 北村雅人
  • Organizer: Columbia University 講演会
  • Int'l Joint Research / Invited
• [Presentation] Donor-Acceptor Bifunctional Catalyst―From DAIB-Zn to Ru/Broensted 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] 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