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Research

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Introduction

Our group is studying new synthetic methods for generating value-added compounds from inexpensive, abundant molecules, focusing particularly on the development of radical or carbene reactions using visible light, electrochemical techniques, or transition metal catalysts. To accelerate the development of these new chemical reactions, our study leverages computational tools, specifically quantum chemical calculations with automated reaction path search algorithms, in collaboration with the Maeda group at Hokkaido University.

Projects

1.1 Radical Reactions

We are developing new radical reactions based on the reactivity of highly reactive radical species with seven valence electrons, estimated using quantum chemical calculations. To generate radical species, we utilize photocatalysts, electrochemical reaction devices, and a flow system that combines these methods. Our current research focuses on radical difunctionalization reactions of ethylene and radical fixation reactions of carbon dioxide (CO2). The transformations of inexpensive, abundant gaseous molecules into valuable compounds can contribute to the realization of a sustainable society.

Press Release and Research Introduction Articles

Representative papers

  1. Trans-Selective Carboxylative Cyclization of 1,6-Dienes Using the CO2 Radical Anion

    Song, Y.; Hayashi, H.*; Mangaonkar, S.; Mita, T.* Chem. Lett. 2024, 53, upae149.

    DOI : 10.1093/chemle/upae149

  2. Strain-Releasing Ring-Opening Diphosphinations for the Synthesis of Diphosphine Ligands with Cyclic Backbones

    Krishnan, C. G.; Takano, H.; Katsuyama, H.; Kanna, W.; Hayashi, H.; Mita, T.* JACS Au 2024, 4, in press.

    DOI : 10.1021/jacsau.4c00347

  3. γ-Butyrolactone Synthesis from Allylic Alcohols Using the CO2 Radical Anion

    Mangaonkar, S. R.; Hayashi, H.; Kanna, W.; Debbarma, S.; Harabuchi, Y.; Maeda, S.*; Mita, T.* Precis. Chem. 2024, 2, 88 - 95.

    DOI : 10.1021/prechem.3c00117

  4. Synthesis of Bicyclo[1.1.1]pentane (BCP)-Based Straight-Shaped Diphosphine Ligands

    Takano, H.; Katsuyama, H.; Hayashi, H.; Harukawa, M.; Tsurui, M.; Shoji, S.; Hasegawa, Y.; Maeda, S.; Mita, T.* Angew. Chem., Int. Ed. 2023, 62, e202303435.

    DOI : 10.1002/anie.202303435

  5. Oxidation and Reduction Pathways in the Knowles Hydroamination via a Photoredox-Catalyzed Radical Reaction

    Harabuchi, Y.*; Hayashi, H.; Takano, H.; Mita, T.; Maeda, S.* Angew. Chem., Int. Ed. 2023, 62, e202211936.

    DOI : 10.1002/anie.202211936

  6. Photoredox/HAT-Catalyzed Dearomative Nucleophilic Addition of the CO2 Radical Anion to (Hetero)Aromatics

    Mangaonkar, S. R.; Hayashi, H.; Takano, H.; Kanna, W.; Maeda, S.; Mita, T.* ACS Catal. 2023, 13, 2482 - 2488.

    DOI : 10.1021/acscatal.2c06192

  7. A Theory-driven Synthesis of Symmetric and Unsymmetric 1,2-Bis(diphenylphosphino)ethane Analogues via Radical Difunctionalization of Ethylene

    Takano, H.; Katsuyama, H.; Hayashi, H.; Kanna, W.; Harabuchi, Y.; Maeda, S.*; Mita, T.* Nat. Commun. 2022, 13, 7034.

    DOI : 10.1038/s41467-022-34546-5

  8. Electrochemical Dearomative Dicarboxylation of Heterocycles with Highly Negative Reduction Potentials

    You, Y.; Kanna, W.; Takano, H.; Hayashi, H.; Maeda, S.*; Mita, T.* J. Am. Chem. Soc. 2022, 144, 3685 - 3695.

    DOI : 10.1021/jacs.1c13032

1.2 Ionic Reactions

We study reactions using highly reactive chemical species with six valence electrons that do not satisfy the octet rule, such as carbenes, nitrenes, benzynes, and carbocations. In this research program, we leverage an artificial force induced reaction method, which can automatically search for chemical reaction pathways using quantum chemical calculations. Based on this computation-based strategy, we have reported new methods to prepare difluoroglycine derivatives and fluorinated N-heterocycles using difluorocarbene as the active species.

Press Release and Research Introduction Articles

Representative papers

  1. In Silico Reaction Screening with Difluorocarbene for N-Difluoroalkylative Dearomatization of Pyridines

    Hayashi, H.; Katsuyama, H.; Takano, H.; Harabuchi, Y.; Maeda, S.*; Mita, T.* Nat. Synth. 2022, 1, 804 - 814.

    DOI : 10.1038/s44160-022-00128-y

  2. Synthesis of Difluoroglycine Derivatives from Amines, Difluorocarbene, and CO2: Computational Design, Scope, and Application

    Hayashi, H.; Takano, H.; Katsuyama, H.; Harabuchi, Y.; Maeda, S.*; Mita, T.* Chem. Eur. J. 2021, 27, 10040 - 10047.

    DOI : 10.1002/chem.202100812

  3. Discovery of a Synthesis Method for a Difluoroglycine Derivative Based on a Path Generated by Quantum Chemical Calculations

    Mita, T.*; Harabuchi, Y.; Maeda, S.* Chem. Sci. 2020, 11, 7569 - 7577.

    DOI : 10.1039/D0SC02089C

1.3 Transition Metal Catalyzed Reactions


We have developed new methods to activate bonds that are difficult to cleave without transition metal catalysts, such as C–H and C–C bonds, transforming them into valuable functionalities. Recently, we developed a method for the direct carboxylation of C–H bonds using carbon dioxide. Additionally, we are working on developing artificial metalloenzymes to control selectivities in radical reactions that are difficult to achieve with small molecule catalysis.

Press Release and Research Introduction Articles

Representative papers

  1. Carboxylation of a Palladacycle Formed via C(sp3)-H Activation: Theory-Driven Reaction Design

    Kanna, W.; Harabuchi, Y.; Takano, H.; Hayashi, H.; Maeda, S.*; Mita, T.* Chem. Asian J. 2021, 16, 4072 - 4080.

    DOI : 10.1002/asia.202100989

  2. Cobalt-Catalyzed Allylic C(sp3)-H Carboxylation with CO2

    Michigami, K.; Mita, T.*; Sato, Y.* J. Am. Chem. Soc. 2017, 139, 6094 - 6097.

    DOI : 10.1021/jacs.7b02775

  3. Highly Regioselective Palladium-Catalyzed Carboxylation of Allylic Alcohols with CO2

    Mita, T.*; Higuchi, Y.; Sato, Y.* Chem. Eur. J. 2015, 21, 16391 - 16394.

    DOI : 10.1002/chem.201503359

1.4 Pericyclic Reactions

Pericyclic Reactions, processes with 100% atom efficiency, are ideally suited for reaction predictions in computational chemistry. Utilizing predictions based on the Woodward-Hoffmann rules, it opens the possibility of identifying unknown reaction modes. We are actively pursuing research to further develop these advancements.

Press Release and Research Introduction Articles

Representative papers

  1. Prediction of High-Yielding Single-Step or Cascade Pericyclic Reactions for the Synthesis of Complex Synthetic Targets

    Mita, T.*; Takano, H.; Hayashi, H.; Kanna, W.; Harabuchi, Y.; Houk, K. N.; Maeda, S.* J. Am. Chem. Soc. 2022, 144, 22985 - 23000.

    DOI : 10.1021/jacs.2c09830

ICReDD Hokkaido University
World Premier International
ERATO
JST
デジタル有機合成
Green Catalysis

Contact

Tsuyoshi Mita

E-mail： tmita@icredd.hokudai.ac.jp