KEIO RESEARCHERS INFORMATION SYSTEM

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 博士（工学）, Nagoya University, Coursework, 2014.03

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Nanotechnology/Materials / Structural organic chemistry and physical organic chemistry

• Nanotechnology/Materials / Structural organic chemistry and physical organic chemistry (有機分子触媒、反応開発)

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Organic synthesis

• Organic chemistry

• 反応開発

• 有機分子触媒

• 有機化学

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Books 【 Display / hide 】

Books 【 Display / hide 】

• Trichloroperoxyacetamidic Acid

  Robert D Bach, Ryosuke Tsutsumi, Daisuke Uraguchi, Takashi Ooi, Wiley, 2018.03

  • Access to Document (DOI)

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• TriQuinazoline and Related Quinoline/Quinazoline Cyclic Trimers: Unified Synthesis, Planar Discotic Architecture, and Proton Dynamics in an Atomic-Scale Cavity

  Takuya Sakurai, Ryosuke Tsutsumi, Naoya Kumagai

  Chemistry of Materials 38 ( 5 ) 2453 - 2463 2026.02

  Accepted,  ISSN  08974756

  　View Summary

  Heteroatom-doped graphitic materials, particularly those bearing nitrogen, have attracted considerable attention because of their unique physicochemical properties, which are unattainable in pristine carbon frameworks. To rigorously investigate the effects of doping and to enable fine-tuning of their functions at the atomic scale, bottom-up synthesis of well-defined molecular surrogates provides a powerful approach. Herein, we report the design, synthesis, and physicochemical characterization of a series of quinoline/quinazoline cyclic trimers, TriQuinoline (TQ, Q3), Q2Qz1, Q1Qz2, and TriQuinazoline (TQz, Qz3), featuring an atomic-sized central cavity surrounded by three pyridinic nitrogens that mirrors the local topology of nitrogen-doped graphene defects. A modular synthetic strategy enabled facile access to all of the quinazoline-containing congeners. Systematic X-ray analysis and computational studies revealed increasing molecular planarity with increasing quinazoline incorporation, arising from stepwise elimination of destabilizing CH···HC contacts and the emergence of favorable CH···N interactions. Spectroscopic and theoretical studies demonstrated that quinazoline substitution progressively decreases the proton affinity at the central cavity owing to the electron-withdrawing nature of the quinazoline units, which markedly accelerates proton exchange. Even with these electronic modifications, supramolecular association with polycyclic aromatics, such as coronene and [12]cycloparaphenylene ([12]CPP), substantially remained preserved upon quinazoline incorporation. These findings highlight the cooperative interplay of structural planarity and heteroatom substitution in dictating the properties of discotic heteroaromatics, offering a versatile platform for material design.

  • Access to Document (DOI)

• DiazaChrysenes (DC): Nitrogen-Containing π-Extended Molecules for Photocatalytic C–H Amination

  Wei Xu, Atsushi Iwai, Itsuki Nagasaka, Satsuki Watanabe, Ryosuke Tsutsumi, Naoya Kumagai

  Organic Letters 27 ( 39 ) 10937 - 10942 2025.10

  Research paper (scientific journal), Accepted,  ISSN  15237060

  　View Summary

  We report a new class of nitrogen-containing π-extended heterocycles, DiazaChrysenes (DCs), and their dimeric analogues (dDCs) as metal-free photocatalysts for C–H amination. DCs featuring a quinolino[1,2-c]quinazolin-5-ium core were synthesized via electrophilic amide activation and arylation. The resulting compounds displayed tunable photophysical and redox properties, with CF<inf>3</inf>-substituted DCs enabling the C–H amination of arenes with azoles under visible light and aerobic conditions, achieving yields up to 85%. The reaction tolerated a range of arene and azole substrates without requiring metal salts or additives. In contrast, dDCs exhibited diminished activity, likely due to their extended π-curvature. Computational studies, including NCI, ACID, and NICS analyses, revealed locally aromatic but electronically isolated π-systems and deshielded central 8-membered cores. This work highlights the utility of DC scaffolds as synthetically accessible and redox-tunable organic photocatalysts.

  • Access to Document (DOI)

• Enlarged‐TriQuinoline (Enl‐TQ): Disparity in Chemical Behaviors by Geometric Scaling of the Trimeric Quinoline Ring System

  Mai Yamashita, Ryosuke Tsutsumi, Toi Kobayashi, Naoya Kumagai

  Chemistry – An Asian Journal 20 ( 17 )  2025.09

  Research paper (scientific journal), Accepted,  ISSN  18614728

  　View Summary

  TriQuinoline (TQ), a quasi-planar cyclic quinoline trimer concatenated at the 2,8-positions in a head-to-tail arrangement, strongly captures a proton at the 12-membered inner cycle and exhibits unusual physicochemical properties, including unexpected water solubility and the ability to engage in complexation with other π-conjugated molecules. In this study, we designed and synthesized its expanded analog, coined Enlarged-TriQuinoline (Enl-TQ), in which three alkyne units are embedded between three quinoline units to acquire an expanded planar 18-membered ring system. DFT calculations and X-ray crystallographic analysis revealed its planar architecture with three inwardly facing pyridinic nitrogen atoms. Despite its structural similarity to TQ, Enl-TQ displayed distinct host capability and photophysical characteristics.

  • Access to Document (DOI)

• Expeditious Access to the B3NO2 Heterocycle Enabling Modular Derivatization.

  Ryosuke Tsutsumi, Nobuaki Kashiwagi, Naoya Kumagai

  The Journal of organic chemistry (Journal of Organic Chemistry)  88 ( 9 ) 6247 - 6251 2023.05

  Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  00223263

  　View Summary

  DATB (1,3-dioxa-5-aza-2,4,6-triborinane) is a unique six-membered heterocycle exhibiting proficient catalytic activity in direct dehydrative amidation. Reported herein is an improved synthetic protocol for DATB derivatives featuring a concise two-step chromatography-free process. Suzuki-Miyaura coupling assembled 2,6-dibromoaniline derivatives and 1,2-phenylenediboronic acid to afford dimeric B-spiroborate salts. Acidic untying of the spiroborates gave rise to the DATB ring system with various substituents.

  • Access to Document (DOI)

• Azo-tagged C4N4 fluorophores: unusual overcrowded structures and their application to fluorescent imaging.

  Miki Kohei, Naoki Takizawa, Ryosuke Tsutsumi, Wei Xu, Naoya Kumagai

  Organic & biomolecular chemistry (Organic and Biomolecular Chemistry)  21 ( 14 ) 2889 - 2893 2023

  Research paper (scientific journal), Joint Work, Accepted,  ISSN  14770520

  　View Summary

  The C4N4 fluorophore is an intense fluorescence emitter featuring a 2,5-diaminopyrimidine core comprising four carbon and four nitrogen atoms. A series of C4N4 derivatives was photochemically dimerized at the 5-amino group, furnishing overcrowded ortho-tetraaryl-substituted diaryl azo compounds with a characteristic skewed structure revealed by X-ray crystallography. The photoquenched azo-C4N4s are useful for fluorescently visualizing cells under hypoxic conditions.

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• Development of highly active amidation catalyst

  Tsutsumi, Ryosuke

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2022

Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Catalytic asymmetric fluorination using CSF sparingly soluble in organic solvent

  Tsutsumi R.

  Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry (Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry)  78 ( 2 ) 158 - 159 2020

  Article, review, commentary, editorial, etc. (scientific journal), Single Work,  ISSN  00379980

  　View Summary

  Metal fluorides such as KF and CsF are inexpensive and easy-to-handle nucleophilic fluorinating reagents while their insolubility in most organic solvents often causes a problem in their synthetic use. In this review, examples of nucleophilic fluorination promoted by a hydrogen-bonding donor are described. Moreover, a recent research on asymmetric nucleophilic fluorination using a chiral hydrogen-bond donor catalyst is introduced.

  • Access to Document (DOI)

• Cover Feature: Enantioselective Electrophilic Cyanation of Boron Enolates: Scope and Mechanistic Studies (Chem. Eur. J. 64/2018)

  Takaya Nagata, Atsuko Tamaki, Kensuke Kiyokawa, Ryosuke Tsutsumi, Masahiro Yamanaka, Satoshi Minakata

  Chemistry – A European Journal (Wiley)  24 ( 64 ) 16926 - 16926 2018.11

  • Access to Document (DOI)

• 忘れられた反応剤Davis’オキサジリジン

  堤 亮祐, 浦口大輔, 大井貴史

  月刊化学 2013 ( 10 ) 66 - 67 2013.10

  Article, review, commentary, editorial, etc. (scientific journal), Joint Work

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• 光触媒機能統合型DATBを用いる化学選択的シアノピリジン変換反応

  木名瀬佑亮、堤亮祐、熊谷直哉

  [Domestic presentation]  日本化学会第106春季年会 (千葉) , 

  2026.03

  , 

  Poster presentation

• TriQuinazoline：1原子欠損型平⾯芳⾹族分⼦群の平面性・電子特性精査

  櫻井拓也, 堤亮祐, 熊谷直哉

  [Domestic presentation]  日本化学会第106春季年会 (千葉) , 

  2026.03

  , 

  Oral presentation (general)

• 特異ヘテロ六員環を擁する協奏機能型触媒を用いたカルボン酸変換反応の開拓

  田井喜輝、堤亮祐、近藤樹、原渕祐、前田理、熊谷直哉

  [Domestic presentation]  日本化学会第106春季年会 (千葉) , 

  2026.03

  , 

  Poster presentation

• １原子欠損型完全平面芳香族化合物TriQuinazolineの合成と物理化学的特性精査

  櫻井拓也, 堤亮祐, 熊谷直哉

  [Domestic presentation]  第52回有機典型元素化学討論会 (茨城) , 

  2025.12

  , 

  Oral presentation (general)

• 環状キノリン3量体の幾何学的スケーリングによる物理化学的特性の変化

  山下舞，堤亮祐，小林透威，熊谷直哉

  [Domestic presentation]  第54回複素環化学討論会 (東京) , 

  2025.10

  , 

  Poster presentation

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• 特殊ヘテロ環の複合機能化を鍵とするカルボン酸原料を用いる多様な触媒的分子変換

  2023.04

  -

  2026.03

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), Principal investigator

  　View Summary

  現在、アミドは専らカルボン酸とアミンに対し縮合剤を作用させて合成されるが、カルボン酸に対して量論量以上の縮合剤を投入する必要がある点、付随して縮合剤に由来する量論量以上の廃棄物が生成する点が大きな問題となる。そのためグリーンケミストリーの観点から、量論量の試薬を排したカルボン酸とアミンの触媒的脱水縮合が古くから研究されている。本研究では、B3NO2型ヘテロ6員環を有する1,3-Dioxa-5-Aza-2,4,6-TriBorinane (DATB) のアミド結合形成触媒能に着目し、本年度は工業的応用を視野に入れた触媒活性のさらなる向上とDATBの触媒機構に着目した新規触媒反応の開発に取り組んだ。具体的には、DATB分子内に基質であるカルボン酸またはアミンの認識部位を組み込んだ新規基質認識型DATBの開発を目指した。最近開発したDATBの改良合成法を駆使することで設計した触媒の多くは実際に合成可能であり、モデル基質を用いた触媒活性評価を実施した。現在のところ、オリジナルのDATBを凌駕する活性を有する誘導体は見出していないが、今後さらなる誘導体化により構造活性相関を精査することで、高活性触媒の導出を目指す。また、これまで未開拓であったDATBを用いるアミド化以外の触媒的合成法の開発を志向し、本年度は遷移金属触媒との協働を念頭に、金属配位部位を導入した複合機能型DATBの創出に取り組んだ。これまでに、遷移金属に配位可能な官能基を有するいくつかの誘導体を合成しており、一部については数種の金属塩との錯形成を示唆する実験結果が得られた。今後金属錯体を用いた新規触媒的分子変換の開拓を目指す。

• Expeditious Sophistication of Seed Molecular Entities Aided by Theory and Machine Learning

  2023.04

  -

  2026.03

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Transformative Research Areas (B), No Setting

• N/A

  2020.04

  -

  2021.03

  Fukuoka Naohiko Memorial Foundation, Principal investigator

• Development of hydrogen bond-donating asymmetric Lewis acid catalyst for control of multiple selectivities

  2017.08

  -

  2019.03

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity start-up, TSUTSUMI Ryosuke, Grant-in-Aid for Research Activity start-up, No Setting

  　View Summary

  In the course of investigating the simultaneous control of regio- and stereoselectivity using hydrogen bond-donating chiral Lewis acids, we found that the reaction between γ-butenolide and α-ketoester proceeded at the α-position of γ-butenolide in the presence of bifunctional organobase catalyst. We newly designed a chiral 2,2'-bipyridine-type ligand with a side chain bearing urea functional group as a hydrogen bond donor. This hydrogen bond-donating chiral Lewis acid was found to catalyze various stereoselective reactions.

• 金属過オキソ酸ホスホニウム触媒の創製およびその酸化反応への応用

  2012

  -

  2013

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows, Grant-in-Aid for JSPS Fellows, No Setting

  　View Summary

  本研究ではこれまでに、金属オキソ酸としてアリルアルコールのエポキシ化やスルフィド酸化等への適用が期待できるバナジン酸(VO_3^-)に着目し、キラルアミノボスホニウム-バナジン酸塩触媒の創製およびその不斉酸化反応への適用を試みた。その結果、触媒の調製方法を確立し、その酸化活性を確認したうえで触媒のカチオン構造が反応速度に与える影響に関して、一定の知見を得た。また本触媒をN-スルホニルイミンの酸化反応へ適用する過程で、この形式の反応を金属フリーな条件下、すなわち有機塩基触媒と過酸化水素を用いて実現できる可能性を見出し、種々の条件検討により、有機塩基触媒として光学活性トリアミノイミノホスホランを用いトリクロロアセトニトリルを添加することで、過酸化水素による不斉酸化反応が効率的に進行することを明らかにした。
  本年度は、この類例の無い酸化反応系の詳細についてさらなる検討を行い、触媒構造と反応のエナンチオ選択性との相関および基質適用範囲について精査した。特に、α位に不斉点を有するラセミ体のイミンに対して反応を適用したところ、片方のエナンチオマーが優先して反応し、可能な四つのジアステレオマーのうち一つが高い選択性で生成した。すなわち、触媒のトリアミノイミノホスホランが、イミンのプロキラル面た加えてα位の不斉点をも認識することでN-スルホニルイミンの速度論的光学分割を達成できたといえる。
  本反応は、求電子的酸化剤およびオキシアミノ化試剤として知られるN-スルホニルオキサジリジンを高立体選択的に合成できる一般性の高い方法であると言え、合成化学的に高い価値を有している。また本研究は、キラル塩基触媒により、過酸化水素からより高い酸化力を有するペルオキシイミデートを生成させ制御できることを実証した初めての例である。

Intellectual Property Rights, etc. 【 Display / hide 】

Intellectual Property Rights, etc. 【 Display / hide 】

• DOCK1阻害化合物およびその用途

  Date applied： 特願2018-225753  2018.11 

  Patent

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• STUDY OF MAJOR FIELD (MOLECULAR DESIGN)

  2025

• SEMINAR (MOLECULAR DESIGN)

  2025

• RESEARCH FOR BACHELOR'S THESIS 1

  2025

• PHARMACEUTICAL-ENGLISH SEMINAR

  2025

• ORGANIC SYNTHESIS

  2025

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• 日本薬学会, 

  2021.04

  -

  Present