Development of enantioselective cross-coupling based on dynamic kinetic resolution

• Project/Area Number: 17K17805
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Synthetic chemistry; Organic chemistry
• Research Institution: Nagoya University
• Principal Investigator: Nambo Masakazu 名古屋大学, トランスフォーマティブ生命分子研究所, 特任講師 (10705528)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 不斉クロスカップリング反応 / 動的速度論的光学分割 / 炭素-スルホニル結合活性化 / スルホン / パラジウム触媒 / 銅触媒 / アミノ化 / フッ素化 / 金属-カルベン / 遷移金属触媒 / C-SO2結合活性化

Outline of Final Research Achievements

We have found the dynamic kinetic asymmetric cross-coupling reactions using organosulfones for the synthesis of enantio-enriched triarylmethane derivatives. During the course of this study, Cu-catalyzed amination of benzhydrylsulfones through the Cu-carbene intermediate and Pd-catalyzed desulfonylative cross-coupling reactions of a-fluorinated benzylsulfones have also been developed.

Academic Significance and Societal Importance of the Research Achievements

安価で容易に調製できるラセミ体を原料として有用な光学活性化合物を得る手法として動的速度論的光学分割が注目を集めている。しかしながらラセミ化する基質にしか適用できないため、実施できる反応様式や得られる光学活性化合物の種類に大きな制約を受けてしまうジレンマを抱えているのが現状である。本クロスカップリング反応は従来の制約を打破し、多様な形式の分子変換に応用できる可能性を秘めている。

Research Products

• [Int'l Joint Research] クイーンズ大学(カナダ)
• [Int'l Joint Research] ユバスキュラ大学(フィンランド)
• [Int'l Joint Research] クイーンズ大学/トロント大学(カナダ)
• [Int'l Joint Research] ユバスキュラ大学(フィンランド)
• [Int'l Joint Research] クイーンズ大学(カナダ)
• [Journal Article] Synthesis and Properties of an Au6 Cluster Supported by a Mixed N-Heterocyclic Carbene-Thiolate ligand (2020)
  • Author(s): Salorinne Kirsi、Man Renee W.Y.、Lummis Paul、Hazer Maryan Sabooni Asre、Malola Sami、Yim Jacky C.-H.、Veinot Alex J.、Zhou Wenxia、Hakkinen Hannu、Nambo Masakazu、Crudden Cathleen
  • Journal Title: Chemical Communications Volume: 56 Issue: 45 Pages: 6102-6105
  • DOI: 10.1039/d0cc01482f
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Modular synthesis of α-fluorinated arylmethanes via desulfonylative cross-coupling (2019)
  • Author(s): Nambo Masakazu、Yim Jacky C.-H.、Freitas Luiza B. O.、Tahara Yasuyo、Ariki Zachary T.、Maekawa Yuuki、Yokogawa Daisuke、Crudden Cathleen M.
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 4528-4528
  • DOI: 10.1038/s41467-019-11758-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pyridine-catalyzed desulfonative borylation of benzyl sulfones (2019)
  • Author(s): Maekawa Yuuki、Ariki Zachary T.、Nambo Masakazu、Crudden Cathleen M.
  • Journal Title: Organic & Biomolecular Chemistry Volume: 17 Issue: 31 Pages: 7300-7303
  • DOI: 10.1039/c9ob01099h
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Copper-catalyzed Desulfonylative Cross-coupling of Benzhydryl Sulfones with Azoles (2019)
  • Author(s): Yim Jacky C.-H.、Nambo Masakazu、Tahara Yasuyo、Crudden Cathleen M.
  • Journal Title: Chemistry Letters Volume: 48 Issue: 8 Pages: 975-977
  • DOI: 10.1246/cl.190334
  • NAID: 130007687689
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] N-heterocyclic carbene-functionalized magic-number gold nanoclusters (2019)
  • Author(s): Mina R. Narouz, Kimberly M. Osten, Phillip J. Unsworth, Renee W. Y. Man, Kirsi Salorinne, Shinjiro Takano, Masakazu Nambo, Hannu Hukkinen, Tatsuya Tsukuda, Cathleen M. Crudden et al
  • Journal Title: Nature Chemistry Volume: - Issue: 5 Pages: 419-425
  • DOI: 10.1038/s41557-019-0246-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cu-catalyzed Desulfonylative Amination of Benzhydryl Sulfones (2019)
  • Author(s): Masakazu Nambo, Yasuyo Tahara, Jacky C.-H. Yim, Cathleen M. Crudden
  • Journal Title: Chemistry A Eurpean Journal Volume: 25 Issue: 8 Pages: 1923-1926
  • DOI: 10.1002/chem.201805638
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ultrastable Gold Nanoparticles Modified by Bidentate N-Heterocyclic Carbene Ligands (2018)
  • Author(s): Man Renee W. Y.、Li Chien-Hung、MacLean Michael W. A.、Zenkina Olena V.、Zamora Matthew T.、Saunders Lisa N.、Rousina-Webb Alexander、Nambo Masakazu、Crudden Cathleen M.
  • Journal Title: Journal of the American Chemical Society Volume: 140 Issue: 5 Pages: 1576-1579
  • DOI: 10.1021/jacs.7b08516
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Preparation of Quaternary Centers via Nickel-Catalyzed Suzuki?Miyaura Cross-Coupling of Tertiary Sulfones (2017)
  • Author(s): Ariki Zachary T.、Maekawa Yuuki、Nambo Masakazu、Crudden Cathleen M.
  • Journal Title: Journal of the American Chemical Society Volume: 140 Issue: 1 Pages: 78-81
  • DOI: 10.1021/jacs.7b10855
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Synthesis of Tetraarylmethanes by the Triflic Acid-Promoted Formal Cross-Dehydrogenative Coupling of Triarylmethanes with Arenes (2017)
  • Author(s): Nambo Masakazu、Crudden Cathleen、Yim Jacky、Fowler Kevin
  • Journal Title: Synlett Volume: 28 Issue: 20 Pages: 2936-2940
  • DOI: 10.1055/s-0036-1588563
  • NAID: 120006473514
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pd-Catalyzed Desulfonative Cross-Coupling of Benzylic Sulfone Derivatives with 1,3-Oxazoles (2017)
  • Author(s): Yim Jacky C.-H.、Nambo Masakazu、Crudden Cathleen M.
  • Journal Title: Organic Letters Volume: 19 Issue: 14 Pages: 3715-3718
  • DOI: 10.1021/acs.orglett.7b01510
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Pd-Catalyzed Suzuki-Miyaura Cross-Coupling of a-Fluorinated Benzylic Triflones (2019)
  • Author(s): Masakazu Nambo, Jacky C.-H. Yim, Yasuyo Tahara, Luiza B. O. Freitas, Yuuki Maekawa, Zachary T. Ariki, Cathleen M. Crudden
  • Organizer: 27th International Society of Heterocyclic Chemistry Congress
  • Int'l Joint Research
• [Presentation] 古くて新しい炭素-スルホニル結合活性化反応の開発 (2019)
  • Author(s): Masakazu Nambo
  • Organizer: 有機金属若手の会
  • Invited
• [Presentation] Pd-Catalyzed Suzuki-Miyaura Cross-Coupling of a-Fluorinated Benzylic Triflones (2019)
  • Author(s): Masakazu Nambo, Jacky C.-H. Yim, Yasuyo Tahara, Luiza B. O. Freitas, Yuuki Maekawa, Zachary T. Ariki, Cathleen M. Crudden
  • Organizer: 第66回有機金属化学討論会
• [Presentation] Pd-Catalyzed Suzuki-Miyaura Cross-Coupling of a-Fluorinated Benzylic Triflones (2019)
  • Author(s): Masakazu Nambo
  • Organizer: Tateshina Conference on Organic Chemistry
  • Int'l Joint Research
• [Presentation] Desulfonylative Transformations of a-Fluorinated Benzylic Sulfones (2019)
  • Author(s): Masakazu Nambo, Jacky C.-H. Yim, Yasuyo Tahara, Luiza B. O. Freitas, Yuuki Maekawa, Zachary T. Ariki, Cathleen M. Crudden
  • Organizer: 第99春季年会
• [Presentation] Modular Synthesis of Multiply-arylated Alkanes through Desulfonylative Cross-Coupling Reactions (2018)
  • Author(s): Masakazu Nambo, Jacky C.-H. Yim, Zachary T. Ariki, Yuuki Maekawa, Kevin G. Fowler, Cathleen M. Crudden
  • Organizer: International Symposium on Main Group Chemistry Directed towards Organic Synthesis (MACOS)
  • Int'l Joint Research / Invited
• [Presentation] Pd- and Ni-Catalyzed Desulfonylative Cross-Coupling Reactions of Benzylic Sulfone Derivatives (2018)
  • Author(s): Masakazu Nambo, Jacky C.-H. Yim, Zachary T. Ariki, Yuuki Maekawa, Cathleen M. Crudden
  • Organizer: 28th International Symposium on the Organic Chemistry of Sulfur (ISOCS-28)
  • Int'l Joint Research / Invited
• [Presentation] Cu-Catalyzed Desulfonylative Amination of Benzhydryl Sulfone Derivatives via a Cu-Carbene Intermediate (2018)
  • Author(s): Masakazu Nambo, Yasuyo Tahara, Jacky C.-H. Yim, Cathleen M. Crudden
  • Organizer: 第65回有機金属化学討論会
• [Presentation] Modular Synthesis of Multiply-arylated Alkanes through Desulfonylative Cross-Coupling Reactions (2018)
  • Author(s): Masakazu Nambo, Jacky C.-H. Yim, Zachary T. Ariki, Yuuki Maekawa, Kevin G. Fowler, Cathleen M. Crudden
  • Organizer: 第18回日韓有機金属・錯体化学シンポジウム
  • Int'l Joint Research
• [Presentation] Modular Synthesis of Fluorinated Arylmethane Derivatives through Desulfonylative Reactions (2018)
  • Author(s): Masakazu Nambo, Yasuyo Tahara, Jacky C.-H. Yim, Luiza B. O. Freitas, Yuuki Maekawa, Zachary T. Ariki, Cathleen M. Crudden
  • Organizer: The 14th International Kyoto Conference on New Aspects of Organic Chemistry (IKCOC-14)
  • Int'l Joint Research
• [Presentation] New Chemical Transformations of Organosulfones through C-SO2 Activation (2018)
  • Author(s): Masakazu Nambo
  • Organizer: 第98春季年会
  • Invited
• [Presentation] Pd-Catalyzed Arylation of Methyl Sulfone Derivatives via C-SO2 Activation: Mechanistic Studies and Application (2017)
  • Author(s): Masakazu Nambo, Kohsuke Usui, Daisuke Yokogawa, Jacky C.-H. Yim, Cathleen M. Crudden
  • Organizer: 第64回有機金属化学討論会
• [Presentation] Pd-Catalyzed Desulfonative Cross-Coupling Reactions of Fluorinated Sulfone Derivatives (2017)
  • Author(s): Masakazu Nambo, Jacky C.-H. Yim, Cathleen M. Crudden
  • Organizer: 第40回フッ素化学討論会
• [Remarks] 有機フッ素化合物の新しいビルドアップ構築法 ～硫黄官能基が導く逐次的分子変換～
  • URL: https://www.chem-station.com/blog/2019/12/desulfonylative.html
• [Remarks] 医農薬品の開発に朗報！ ～ 有機フッ素化合物の新しいビルドアップ構築法 ～
  • URL: http://www.itbm.nagoya-u.ac.jp/ja/research/2019/10/post-16.php
• [Remarks] SYNLETT Best Paper Award Winners 2017
  • URL: https://www.thieme.de/en/thieme-chemistry/2017-winners-123200.htm
• [Remarks] SYNLETT Best Paper Award 2017を受賞しました
  • URL: http://www.itbm.nagoya-u.ac.jp/ja/news/2018/02/Crudden-Synlett.php