Ligand Design for Catalytic Asymmetric C-H Bond Functinalization

• Project/Area Number: 18H03906
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 33:Organic chemistry and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Sawamura Masaya 北海道大学, 理学研究院, 教授 (40202105)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥43,810,000 (Direct Cost: ¥33,700,000、Indirect Cost: ¥10,110,000); Fiscal Year 2021: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000); Fiscal Year 2020: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000); Fiscal Year 2019: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000); Fiscal Year 2018: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
• Keywords: 不斉合成 / C-H活性化 / 非古典的水素結合 / ロンドン分散力 / 銅触媒 / アリル化 / ホスフィン配位子 / 触媒 / 有機合成 / 量子化学計算 / 不斉触媒 / 配位子 / ホスフィン / NHC配位子 / ホウ素化 / ナノ材料 / 触媒・化学プロセス / C-H結合活性化 / β-ラクタム / アルキルボロン

Outline of Final Research Achievements

<1. Application of prolinol-phosphine ligands> We developed new reactions and ligands focusing on non-classical hydrogen bonding with sp3-C-H bonds. Furtheremore, copper-catalyzed asymmetric Kinugasa reaction and silver-catalyzed isocyanoacetate asymmetric Aldol reactions were developed. We also clarified the importance of sp3-C-H/π interaction in the study of Ir-catalyzed hydrogen transfer asymmetric reduction of ketones.
<2. Application of phenol-carbene ligands> We developed a copper-catalyzed reaction between organic boron and silicon compounds. These studies led to the discovery of a visible light-driven copper-catalyzed asymmetric allyl-position acylation reaction.
<3. Pd-catalyzed asymmetric allylation of alkylazaarene> Highly enantioelectivities have been achieved with a cleft-type monodentate diamidophosphite ligand.

Academic Significance and Societal Importance of the Research Achievements

本研究は酸性度の異なるsp-C-H、sp2－C－H、sp3－C－Hを対象とした総合的な取り組みにおいて、触媒と反応基質の間に働く非共有結合性相互作用の重要性に光を当てることで、化学反応の原理を深く理解することに貢献した。不斉配位子・触媒の設計によって立体選択性を追求しつつ、反応機構を実験と理論化学の組み合わせで検証することによって、触媒設計・反応設計の発展に大きく貢献した。非極性のsp3－C－Hがsp3－C－H/O水素結合やロンドン分散力を通じて化学反応の促進や制御に大きく関わり、従来の立体障害の概念とは真逆の効果を誘起しうることを示したことの意義は特に顕著である。

Research Products

• [Int'l Joint Research] Ubon Ratchathani University(タイ)
• [Journal Article] Iridium-Catalyzed Alkene-Selective Transfer Hydrogenation with 1,4-Dioxane as Hydrogen Donor (2020)
  • Author(s): Zhang Deliang、Iwai Tomohiro、Sawamura Masaya
  • Journal Title: organic letter Volume: 21 Pages: 5867-5872
  • DOI: 10.1021/acs.orglett.9b01989
  • NAID: 120006869882
  • Peer Reviewed
• [Journal Article] Asymmetric Synthesis of a-Aminoboronates via Rhodium-Catalyzed Enantioselective C(sp3)-H Borylation (2020)
  • Author(s): Reyes, R. L., Sato, M., Iwai, T., and Sawamura, M.
  • Journal Title: Journal of the American Chemical Society Volume: 142 Pages: 589-597
  • DOI: 10.1021/jacs.9b12013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Copper-Catalyzed Enantioselective Conjugate Reduction of α,β-Unsaturated Esters with Phenol-Carbene Chiral Ligand (2020)
  • Author(s): Mimura Shohei、Mizushima Sho、Shimizu Yohei、Sawamura Masaya
  • Journal Title: Beilstein Journal of Organic Chemistry Volume: 16 Pages: 537-543
  • DOI: 10.3762/bjoc.16.50
  • Peer Reviewed / Open Access
• [Journal Article] A Polystyrene‐Cross‐Linking Tricyclohexylphosphine: Synthesis, Characterization and Applications to Pd‐Catalyzed Cross‐Coupling Reactions of Aryl Chlorides (2019)
  • Author(s): Arashima Junya、Iwai Tomohiro、Sawamura Masaya
  • Journal Title: Chemistry ? An Asian Journal Volume: 14 Pages: 411-415
  • DOI: 10.1002/asia.201801651
  • Peer Reviewed
• [Journal Article] Asymmetric Synthesis of α-Alkylidene-β-Lactams through Copper Catalysis with a Prolinol-Phosphine Chiral Ligand (2019)
  • Author(s): Imai Koji、Takayama Yurie、Murayama Hiroaki、Ohmiya Hirohisa、Shimizu Yohei、Sawamura Masaya
  • Journal Title: Organic Letters Volume: 21 Pages: 1717-1721
  • DOI: 10.1021/acs.orglett.9b00276
  • Peer Reviewed
• [Journal Article] Heterogeneous Nickel‐Catalyzed Cross‐Coupling between Aryl Chlorides and Alkyllithiums Using a Polystyrene‐Cross‐Linking Bisphosphine Ligand (2019)
  • Author(s): Yamazaki Yuki、Arima Nozomi、Iwai Tomohiro、Sawamura Masaya
  • Journal Title: Advanced Synthesis & Catalysis Volume: 361 Pages: 2250-2254
  • DOI: 10.1002/adsc.201801713
  • NAID: 120006798317
  • Peer Reviewed
• [Journal Article] Nickel‐Copper‐Catalyzed Hydroacylation of Vinylarenes with Acyl Fluorides and Hydrosilanes (2019)
  • Author(s): Ueda Yusuke、Iwai Tomohiro、Sawamura Masaya
  • Journal Title: Chemistry - A European Journal Volume: 25 Pages: 9410-9414
  • DOI: 10.1002/chem.201900822
  • NAID: 120006844535
  • Peer Reviewed
• [Journal Article] Iridium-Catalyzed Asymmetric Borylation of Unactivated Methylene C(sp3)-H Bonds (2019)
  • Author(s): Reyes Ronald L.、Iwai Tomohiro、Maeda Satoshi、Sawamura Masaya
  • Journal Title: Journal of the American Chemical Society Volume: 141 Pages: 6817-6821
  • DOI: 10.1021/jacs.9b01952
  • Peer Reviewed
• [Journal Article] Nickel-Catalyzed Decarboxylation of Aryl Carbamates for Converting Phenols into Aromatic Amines (2019)
  • Author(s): Nishizawa Akihiro、Takahira Tsuyoshi、Yasui Kosuke、Fujimoto Hayato、Iwai Tomohiro、Sawamura Masaya、Chatani Naoto、Tobisu Mamoru
  • Journal Title: Journal of the American Chemical Society Volume: 141 Pages: 7261-7265
  • DOI: 10.1021/jacs.9b02751
  • Peer Reviewed
• [Journal Article] Boron-Catalyzed α-Amination of Carboxylic Acids (2019)
  • Author(s): Morisawa Takuto、Sawamura Masaya、Shimizu Yohei
  • Journal Title: Organic Letters Volume: 21 Pages: 7466-7469
  • DOI: 10.1021/acs.orglett.9b02769
  • Peer Reviewed
• [Journal Article] Copper-Catalyzed Enantioselective Coupling between Allylboronates and Phosphates with a Phenol-Carbene Chiral Ligand: Asymmetric Synthesis of Chiral Branched 1,5-Dienes (2018)
  • Author(s): Yasuda, Y.; Ohmiya, H.; Sawamura, M.
  • Journal Title: Synthesis Volume: 印刷中 Pages: 2235-2246
  • DOI: 10.1055/s-0036-1591548
  • Peer Reviewed
• [Journal Article] Enantiocontrol by assembled attractive interactions in copper-catalyzed asymmetric direct alkynylation of α-ketoesters with terminal alkynes: OH-O/sp3-CH-O two-point hydrogen bonding combined with dispersive attractions (2018)
  • Author(s): Schwarzer Martin C.、Fujioka Akane、Ishii Takaoki、Ohmiya Hirohisa、Mori Seiji、Sawamura Masaya
  • Journal Title: Chemical Science Volume: 9 Pages: 3484-3493
  • DOI: 10.1039/c8sc00527c
  • Peer Reviewed / Open Access
• [Journal Article] Palladium-Catalyzed Asymmetric C(sp3)-H Allylation of 2-Alkylpyridines (2018)
  • Author(s): Murakami Ryo、Sano Kentaro、Iwai Tomohiro、Taniguchi Tohru、Monde Kenji、Sawamura Masaya
  • Journal Title: Angew. Chem. Int. Ed. Volume: 57 Pages: 9465-9469
  • DOI: 10.1002/anie.201802821
  • Peer Reviewed
• [Presentation] ホスフィンリガンドを固定した多孔質モノリスによる精密フロー合成 (2020)
  • Author(s): 松本光・星野友・三浦佳子・岩井智弘・澤村正也
  • Organizer: 化学工学会第85年会
• [Presentation] ホウ素触媒を用いるカルボン酸α位アミノ化反応の開発 (2020)
  • Author(s): 森沢 卓斗・清水 洋平・澤村 正也
  • Organizer: 日本化学会 第100春季年会
• [Presentation] キラルプロリノール-ホスフィン-銀触媒を用いたイソシアノ酢酸アミドの不斉アルドール反応 (2020)
  • Author(s): 今井 洸児・藤岡 茜・清水 洋平・澤村 正也
  • Organizer: 日本化学会 第100春季年会
• [Presentation] Copper-Catalyzed Allylic Acylation with Acyl Silanes under Photoirradiation (2020)
  • Author(s): Yusuke Ueda,Tomohiro Iwai, Masaya Sawamura
  • Organizer: 日本化学会 第100春季年会
• [Presentation] Catalytic Hydrogenation and Dehydrogenation of Heterocyclic Compounds Based on C(sp3)-H Activation (2020)
  • Author(s): Deliang Zhang,Tomohiro Iwai, Masaya Sawamura
  • Organizer: 日本化学会 第100春季年会
• [Presentation] Asymmetric Synthesis of α-Aminoboronates via Rhodium-Catalyzed Enantioselective C(sp3)-H Borylation (2020)
  • Author(s): Ronald L. Reyes, Miyu Sato, Tomohiro Iwai, Masaya Sawamura
  • Organizer: 日本化学会 第100春季年会
• [Presentation] ホウ素触媒によるカルボン酸α位アミノ化反応の開発 (2020)
  • Author(s): 清水 洋平・森沢 卓斗・澤村 正也
  • Organizer: 日本薬学会第140年会
• [Presentation] ポリスチレン架橋ホスフィン配位子を用いた触媒開発の展開 (2019)
  • Author(s): 澤村正也
  • Organizer: 新学術領域研究「精密制御反応場」第7回公開シンポジウム
  • Invited
• [Presentation] Ligand-Enabled Selective Borylation of C-H and C(sp3)-H Bonds (2019)
  • Author(s): Masaya Sawamura
  • Organizer: The 27th French-Japanese Symposium on Medicinal and Fine Chemistry
  • Int'l Joint Research / Invited
• [Presentation] Catalytic Enantioselective Borylation of Methylene C-H Bonds (2019)
  • Author(s): Ronald Reyes, Tomohiro Iwai, Satoshi Maeda, Masaya Sawamura
  • Organizer: 第29回 万有福岡シンポジウム
  • Invited
• [Presentation] Enantioselective Methylene C(sp3)-H Borylation (2019)
  • Author(s): Masaya Sawamura
  • Organizer: The 47th Naito Conference on "C-H Activation and Transformation"
  • Int'l Joint Research / Invited
• [Presentation] Iridium-Catalyzed Alkene-Selective Transfer Hydrogenation with 1,4-Dioxane as Hydrogen Donor (2019)
  • Author(s): Deliang Zhang, Tomohiro Iwai, Masaya Sawamura
  • Organizer: 第31回 万有札幌シンポジウム
• [Presentation] Nickel-Copper-Catalyzed Hydroacylation of Vinylarenes with Acyl Fluorides and Hydrosilanes (2019)
  • Author(s): Yusuke Ueda, Tomohiro Iwai, Masaya Sawamura
  • Organizer: 20th IUPAC International Symposium on Organometallic Chemistry Directed Towards Organic Synthesis
  • Int'l Joint Research
• [Presentation] Asymmetric Synthesis of α-Aminoalkylboronates through Rh-Catalyzed Enantioselective C(sp3)-H Borylation (2019)
  • Author(s): Masaya Sawamura, Ronald Reyes, Tomohiro Iwai, Satoshi Maeda
  • Organizer: 20th IUPAC International Symposium on Organometallic Chemistry Directed Towards Organic Synthesis
  • Int'l Joint Research
• [Presentation] Application of Macroporous Polystyrene-Triphenylphosphine Monolith to Palladium-Catalyzed Cross-Coupling Reaction in Flow System (2019)
  • Author(s): Hikaru Matsumoto, Yu Hoshino, Tomohiro Iwai, Masaya Sawamura, Yoshiko Miura
  • Organizer: The 4th International Symposium on Process Chemistry 2019 (ISPC2019)
  • Int'l Joint Research
• [Presentation] Catalytic Enantioselective C(sp3)-H Borylation (2019)
  • Author(s): Masaya Sawamura
  • Organizer: 7th Latin American Symposium on Coordination and Organometallic Chemistry
  • Int'l Joint Research / Invited
• [Presentation] Noncovalent Interactions in Ir-Catalyzed Enantioselective C(sp3)-H Borylation (2019)
  • Author(s): Masaya Sawamura
  • Organizer: 1st International Conferences on Noncovalent Interactions (ICNI-2019)
  • Int'l Joint Research / Invited
• [Presentation] ホウ素触媒と可視光が駆動するカルボン酸α位アリル化反応 (2019)
  • Author(s): 清水洋平・上野雅人・澤村正也
  • Organizer: 第66回有機金属化学討論会
• [Presentation] キラルプロリノール-ホスフィン-銅触媒によるα-アルキリデン-β-ラクタムの不斉合成 (2019)
  • Author(s): 今井洸児・高山ゆりえ・村山大明・大宮寛久・清水洋平・澤村正也
  • Organizer: 第66回有機金属化学討論会
• [Presentation] 1,4-ジオキサンを水素源とするイリジウム触媒水素移動型還元反応 (2019)
  • Author(s): 岩井智弘・張徳良・澤村正也
  • Organizer: 第66回有機金属化学討論会
• [Presentation] Transition-metal catalysis in continuous-flow system using biphasic solvent: Macroporous polystyrene supporting palladium-phosphine complex (2019)
  • Author(s): Hikaru Matsumoto, Yu Hoshino, Tomohiro Iwai, Masaya Sawamura, Yoshiko Miura
  • Organizer: 18th Asian Pacific Confederation of Chemical Engineering Congress (APCChE 2019)
  • Int'l Joint Research
• [Presentation] Catalytic Enantioselective C(sp3)-H Borylation: Mechanism and Applications (2019)
  • Author(s): Masaya Sawamura
  • Organizer: The 9th Junior International Conference on Cutting-Edge Organic Chemistry in Asia (Junior ICCEOCA-9)
  • Int'l Joint Research / Invited
• [Presentation] Polystyrene-Cross-Linking Phosphines for Organometallic Catalysis (2019)
  • Author(s): Tomohiro Iwai, Masaya Sawamura
  • Organizer: The 14th International Conference on Cutting-Edge Organic Chemistry in Asia (ICCEOCA-14)
  • Int'l Joint Research / Invited
• [Presentation] Boron Catalyst and Visible Light-Driven α-Allylation of Carboxylic Acids (2019)
  • Author(s): Yohei Shimizu, Masato Ueno, Masaya Sawamura
  • Organizer: The 14th International Conference on Cutting-Edge Organic Chemistry in Asia (ICCEOCA-14)
  • Int'l Joint Research / Invited
• [Presentation] ヒドロシランおよびフッ化アシルを用いたビニルアレーンのニッケル/銅協働触媒ヒドロアシル化反応 (2019)
  • Author(s): 上田悠介・岩井智弘・澤村正也
  • Organizer: 第23回ケイ素化学協会シンポジウム
• [Presentation] Ligand-Enabled Selective Borylation of C(sp2)-;H and C(sp3)-H Bonds (2019)
  • Author(s): Masaya Sawamura
  • Organizer: NOST Organic Chemistry & Biomolecular Chemistry Conference
  • Int'l Joint Research / Invited
• [Presentation] Rhodium-Catalyzed Asymmetric Borylation of N-adjacent C(sp3)-H Bonds (2019)
  • Author(s): Ronald L. Reyes, Miyu Sato, Tomohiro Iwai, Masaya Sawamura
  • Organizer: The 2nd ICReDD International Symposium
  • Int'l Joint Research
• [Presentation] Boron Catalyst and Visible Light-Driven α-Allylation of Carboxylic Acids (2019)
  • Author(s): Yohei Shimizu, Masato Ueno, Masaya Sawamura
  • Organizer: The 2nd ICReDD International Symposium
  • Int'l Joint Research
• [Presentation] atalytic Enantioselective C(sp3)-H Borylation (2019)
  • Author(s): Masaya Sawamura
  • Organizer: The 2nd ICReDD International Symposium
  • Int'l Joint Research / Invited
• [Presentation] Asymmetric Synthesis of α-Aminoboronates via Rhodium-Catalyzed Enantioselective C(sp3)-H Borylation (2019)
  • Author(s): Masaya Sawamura
  • Organizer: The 2nd Japan Germany Singapore Trilateral Symposium on Precision Synthesis and Catalysis
  • Int'l Joint Research / Invited
• [Presentation] Acceptorless Dehydrogenation of N-Heterocycles with a Polystyrene-Cross-Linking Bisphosphine-Ir Catalyst (2019)
  • Author(s): Deliang Zhang・Tomohiro Iwai・Masaya Sawamura
  • Organizer: 第4回精密制御反応場国際シンポジウム
  • Int'l Joint Research
• [Presentation] Iridium-Catalyzed Alkene-Selective Transfer Hydrogenation with 1,4-Dioxane as Hydrogen Donor (2019)
  • Author(s): Deliang Zhang・Tomohiro Iwai・Masaya Sawamura
  • Organizer: 第4回精密制御反応場国際シンポジウム
  • Int'l Joint Research
• [Presentation] Experimantal and Computational Approach to Innovatve Asymmetric C-H Functionalization (2019)
  • Author(s): Masaya Sawamura
  • Organizer: MANA Seminar
  • Invited
• [Presentation] 配位子設計のおもしろさ (2019)
  • Author(s): 澤村正也
  • Organizer: 日本薬学会東海支部特別講演会
  • Invited
• [Presentation] Enantioselective Borylation of Unactivated C(sp3)-H Bond (2019)
  • Author(s): Masaya Sawamura
  • Organizer: The Hokkaido University & Peking University Joint Symposium
  • Int'l Joint Research / Invited
• [Presentation] 炭素ー炭素結合形成不斉銅触媒反応の開発 (2019)
  • Author(s): 澤村正也
  • Organizer: 2019年度有機合成化学協会総会
  • Invited
• [Presentation] Non-covalent Interactions in Our Studies on Asymmetric Transition Metal Catalysis (2019)
  • Author(s): Masaya Sawamura
  • Organizer: 3rd Workshop of SPP 1807: Central of London dispersion interactions in molecular chemistry
  • Int'l Joint Research / Invited
• [Presentation] 固定化ホスフィンと遷移金属による触媒デザイン (2018)
  • Author(s): 澤村正也
  • Organizer: 第７回JACI／GSCシンポジウム
  • Int'l Joint Research / Invited
• [Presentation] Catalytic Asymmetric Borylation of Unactivated Methylene C-H Bonds (2018)
  • Author(s): Ronald L. Reyes, Tomohiro Iwai, and Masaya Sawamura
  • Organizer: The 28th International Conference on Organometallic Chemistry (ICOMC2018)
  • Int'l Joint Research
• [Presentation] Iridium-Catalyzed Asymmetric Borylation of Methylene C-H Bonds (2018)
  • Author(s): Ronald L. Reyes, Tomohiro Iwai, Satoshi Maeda, and Masaya Sawamura
  • Organizer: The 4th International Symposium on C-H Activation (ISCHA4)
  • Int'l Joint Research / Invited
• [Presentation] 高分子ゲルによる触媒デザイン (2018)
  • Author(s): 澤村正也
  • Organizer: 第67回高分子討論会
  • Invited
• [Presentation] C-H不斉変換触媒の開発 (2018)
  • Author(s): 澤村正也
  • Organizer: 第122回触媒討論会
  • Invited
• [Presentation] 触媒のチカラを引き出す配位子設計と反応開発 (2018)
  • Author(s): 澤村正也
  • Organizer: 第８回CSJ化学フェスタ2018
  • Invited
• [Presentation] Catalytic Enantioselective Borylation of Unactivated Methylene C-H Bonds (2018)
  • Author(s): Masaya Sawamura
  • Organizer: The Junior International Conference on Cutting-Edge Organic Chemistry in Asia
  • Int'l Joint Research / Invited
• [Presentation] 不斉触媒反応と非共有結合相互作用 (2018)
  • Author(s): 澤村正也
  • Organizer: 大塚創薬化学シンポジウム
  • Invited
• [Presentation] Catalytic Asymmetric Borylation of Unactivated Methylene C-H Bonds (2018)
  • Author(s): Masaya Sawamura
  • Organizer: 第6回日英触媒的不斉合成シンポジウム
  • Int'l Joint Research / Invited
• [Presentation] Iridium-Catalyzed Enantioselective Borylation of Methylene C-H Bonds Enablebled by Chiral Monophosphite Ligands (2018)
  • Author(s): Masaya Sawamura
  • Organizer: International Conference on Phosphorus, Boron and Silicon (PBSi 2018)
  • Int'l Joint Research
• [Remarks] 北海道大学大学院理学研究院化学部門 有機金属化学研究室 ホームページ
  • URL: https://wwwchem.sci.hokudai.ac.jp/~orgmet/index.php?id=1
• [Remarks] Hokkaido Univ., Organometallic Chemistry Lab.
  • URL: https://wwwchem.sci.hokudai.ac.jp/~orgmet/index.php?id=25
• [Remarks] 北海道大学大学院理学研究院化学部門 有機金属化学研究室 ホームページ
  • URL: https://wwwchem.sci.hokudai.ac.jp/~orgmet/
• [Remarks] Organometallic Chemistry Lab. Home Page
  • URL: https://wwwchem.sci.hokudai.ac.jp/~orgmet/index.php?id=25