Updated on 2022/05/26

写真a

 
MUTO, Kei
 
Affiliation
Affiliated organization, Waseda Institute for Advanced Study
Job title
Associate Professor(non-tenure-track)

Concurrent Post

  • Faculty of Science and Engineering   School of Advanced Science and Engineering

Education

  • 2015.10
    -
    2016.03

    Nagoya University   Institute of Transformative BioMolecule (WPI-ITbM)  

  • 2011.04
    -
    2015.09

    Nagoya University   Department of Chemistry  

  • 2007.04
    -
    2011.03

    Nagoya University   School of Science   Department of Chemistry  

  • 2004.04
    -
    2007.03

    Okazaki High School  

Degree

  • Nagoya Univeristy   PhD. Science

Research Experience

  • 2022.04
    -
    Now

    Waseda University   Institue for Advanced Study   Associate Professor

  • 2020.04
    -
    2022.03

    Waseda University   Institute for Advanced Study   Assistant Professor

  • 2018.04
    -
    2020.03

    Waseda University   Department of Applied Chemistry, School of Advanced Science and Engineering   Assistant Professor

  • 2016.04
    -
    2018.03

    Waseda University   Department of Applied Chemistry, School of Advanced Science and Engineering   Assistant Professor

  • 2013.04
    -
    2015.09

    Nagoya University   Graduate School of Science   JSPS DC1

Professional Memberships

  • 2017.09
    -
    Now

    KINKA CHEMICAL SOCIETY

  •  
     
     

    The Japanese Society for Process Chemistry

  •  
     
     

    The Society of Synthetic Organic Chemistry, Japan

  •  
     
     

    Chemical Society of Japan

 

Research Areas

  • Synthetic organic chemistry

  • Bioorganic chemistry

  • Structural organic chemistry and physical organic chemistry

Papers

  • Convergent Azaspirocyclization of Bromoarenes with N-Tosylhydrazones by a Palladium Catalyst

    Aika Yanagimoto, Yota Uwabe, Qikun Wu, Kei Muto, Junichiro Yamaguchi

    ACS Catalysis   11 ( 16 ) 10429 - 10435  2021.08

    Authorship:Corresponding author

    DOI

  • Ni-Catalyzed Aryl Sulfide Synthesis through an Aryl Exchange Reaction

    Ryota Isshiki, Miki B. Kurosawa, Kei Muto, Junichiro Yamaguchi

    Journal of the American Chemical Society   143 ( 27 ) 10333 - 10340  2021.07

     View Summary

    A Ni-catalyzed aryl sulfide synthesis through an aryl exchange reaction between aryl sulfides and a variety of aryl electrophiles was developed. By using 2-pyridyl sulfide as a sulfide donor, this reaction achieved the synthesis of aryl sulfides without using odorous and toxic thiols. The use of a Ni/dcypt catalyst capable of cleaving and forming aryl-S bonds was important for the aryl exchange reaction between 2-pyridyl sulfides and aryl electrophiles, which include aromatic esters, arenol derivatives, and aryl halides. Mechanistic studies revealed that Ni/dcypt can simultaneously undergo oxidative additions of aryl sulfides and aromatic esters, followed by ligand exchange between the generated aryl-Ni-SR and aryl-Ni-OAr species to furnish aryl exchanged compounds.

    DOI PubMed

  • Development of Pd-catalyzed denitrative couplings

    Kitty K. Asahara, Myuto Kashihara, Kei Muto, Yoshiaki Nakao, Junichiro Yamaguchi

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry   79 ( 1 ) 11 - 21  2021.01

     View Summary

    Transition metal-catalyzed cross-coupling between aryl halides and nucleophiles is one of the most reliable C-C and C-heteroatom bond forming reactions. However, preparation of haloarenes usually requires multi-step operation, making the whole cross-coupling process inefficient. Nitroarenes, synthesized by a single-step nitration of arenes, can be attractive alternatives as electrophiles in cross-coupling methodology, but inherent inertness of C(sp 2)-NO 2 bonds toward metal catalysts has been a bottleneck of general denitrative transformations. Recently, we have overcome this obstacle and achieved direct activation of Ar-NO 2 bonds by using Pd/BrettPhos catalysis. Herein, we describe the development of denitrative couplings by Pd/BrettPhos catalyst and its unique suitability from a mechanistic point of view. Deep understanding of reaction mechanism also enabled us to design more active Pd/NHC system.

    DOI

  • Catalytic three-component C-C bond forming dearomatization of bromoarenes with malonates and diazo compounds

    Hiroki Kato, Itsuki Musha, Masaaki Komatsuda, Kei Muto, Junichiro Yamaguchi

    Chemical Science   11 ( 33 ) 8779 - 8784  2020.09  [Refereed]

    Authorship:Corresponding author

     View Summary

    A Pd-catalyzed dearomative three-component C-C bond formation of bromoarenes with diazo compounds and malonates was developed. Various bromoarenes ranging from benzenoids to azines and heteroles were transformed to the corresponding substituted alicyclic molecules. The key to this reaction is the generation of a benzyl-palladium intermediate, which reacts with malonates to form a Pd-O-enolate species. Strikingly, the present method enabled rapid access to multi-substituted alicycles through subsequent elaboration of dearomatized products. This journal is

    DOI

  • Transition-Metal-Catalyzed Denitrative Coupling of Nitroarenes

    Kei Muto, Toshimasa Okita, Junichiro Yamaguchi

    ACS Catalysis   10 ( 17 ) 9856 - 9871  2020.09

     View Summary

    Functionalization of arenes is a topic of central importance in diverse fields ranging from medicinal chemistry to materials science. Metal-catalyzed cross-coupling and nucleophilic aromatic substitution are among the most reliable methods to access functionalized arenes. In these reactions, haloarenes are often used as a versatile synthetic platform to introduce various functional groups. However, haloarenes are typically prepared from the corresponding nitroarenes through the classic sequence of reduction, diazotization, and halogenation. Thus, haloarene cross-coupling can become a multistep transformation overall. To avoid this lengthy sequence, the direct utilization of nitroarenes has the potential to significantly streamline synthetic processes and, therefore, has attracted attention in the chemistry community from the vantage points of atom- A nd step-economy. In this Review, we comprehensively cover advances in transition-metal-catalyzed denitrative reactions of nitroarenes.

    DOI

  • Pd-catalyzed C4-Dearomative Allylation of Benzyl Ammoniums with Allyltributylstannane

    Yuki Kayashima, Masaaki Komatsuda, Kei Muto, Junichiro Yamaguchi

    Chemistry Letters   49 ( 7 ) 836 - 839  2020.07  [Refereed]

    Authorship:Corresponding author

    DOI

  • Ester dance reaction on the aromatic ring

    Kaoru Matsushita, Ryosuke Takise, Kei Muto, Junichiro Yamaguchi

    Science Advances   6 ( 28 ) eaba7614 - eaba7614  2020.07  [Refereed]

     View Summary

    Aromatic rearrangement reactions are useful tools in the organic chemist’s toolbox when generating uncommon substitution patterns. However, it is difficult to precisely translocate a functional group in (hetero) arene systems, with the exception of halogen atoms in a halogen dance reaction. Here, we describe an unprecedented “ester dance” reaction: a predictable translocation of an ester group from one carbon atom to another on an aromatic ring. Specifically, a phenyl carboxylate substituent can be shifted from one carbon to an adjacent carbon on a (hetero) aromatic ring under palladium catalysis to often give a thermodynamically favored, regioisomeric product with modest to good conversions. The obtained ester moiety can be further converted to various aromatic derivatives through the use of classic and state-of-the-art transformations including amidation, acylations, and decarbonylative couplings.

    DOI

  • Dearomative Allylation of Naphthyl Cyanohydrins by Palladium Catalysis: Catalyst-Enhanced Site Selectivity

    Aika Yanagimoto, Masaaki Komatsuda, Kei Muto, Junichiro Yamaguchi

    Organic Letters   22 ( 9 ) 3423 - 3427  2020.05  [Refereed]

    Authorship:Corresponding author

    DOI

  • Catalytic Deoxygenative Coupling of Aromatic Esters with Organophosphorus Compounds

    Miki B. Kurosawa, Ryota Isshiki, Kei Muto, Junichiro Yamaguchi

    Journal of the American Chemical Society   142 ( 16 ) 7386 - 7392  2020.04  [Refereed]

    DOI

  • Palladium-Catalyzed Mizoroki–Heck Reaction of Nitroarenes and Styrene Derivatives

    Toshimasa Okita, Kitty K. Asahara, Kei Muto, Junichiro Yamaguchi

    Organic Letters   22 ( 8 ) 3205 - 3208  2020.04  [Refereed]

    DOI

  • Ester Transfer Reaction of Aromatic Esters with Haloarenes and Arenols by a Nickel Catalyst

    Ryota Isshiki, Naomi Inayama, Kei Muto, Junichiro Yamaguchi

    ACS Catalysis   10 ( 5 ) 3490 - 3494  2020.03  [Refereed]

    DOI

  • Decarbonylative Synthesis of Aryl Nitriles from Aromatic Esters and Organocyanides by a Nickel Catalyst

    Keiichiro Iizumi, Miki B. Kurosawa, Ryota Isshiki, Kei Muto, Junichiro Yamaguchi

    Synlett    2020

     View Summary

    A decarbonylative cyanation of aromatic esters with aminoacetonitriles in the presence of a nickel catalyst was developed. The key to this reaction was the use of a thiophene-based diphosphine ligand, dcypt, permitting the synthesis of aryl nitrile without the generation of stoichiometric metal- or halogen-containing chemical wastes. A wide range of aromatic esters, including hetarenes and pharmaceutical molecules, can be converted into aryl nitriles.

    DOI

  • Pd-Catalyzed Alkenyl Thioether Synthesis from Thioesters and N-Tosylhydrazones

    Kota Ishitobi, Kei Muto, Junichiro Yamaguchi

    ACS Catalysis   9 ( 12 ) 11685 - 11690  2019.12  [Refereed]

    DOI

  • Pd-Catalyzed Dearomative Three-Component Reaction of Bromoarenes with Diazo Compounds and Allylborates

    Komatsuda Masaaki, Kato Hiroki, Muto Kei, Yamaguchi Junichiro

    ACS CATALYSIS   9 ( 10 ) 8991 - 8995  2019.10  [Refereed]

    Authorship:Corresponding author

    DOI

  • Pd-Catalyzed Denitrative Intramolecular C-H Arylation

    Asahara Kitty K, Okita Toshimasa, Saito Ami N, Muto Kei, Nakao Yoshiaki, Yamaguchi Junichiro

    ORGANIC LETTERS   21 ( 12 ) 4721 - 4724  2019.06  [Refereed]

     View Summary

    A Pd-catalyzed intramolecular C-H arylation of nitroarenes has been developed. Nitroarenes bearing tethered aryl groups at the ortho-position can be readily prepared in one step from 2-halonitroarenes by a nucleophilic aromatic substitution (SNAr). Under Pd/BrettPhos catalysis, activations of the C-NO2 bond as well as the C-H bond on arenes generated the corresponding biaryl linkage in moderate to excellent yields.

    DOI

  • Synthesis of a Heptaarylisoquinoline: Unusual Disconnection for Constructing Isoquinoline Frameworks

    Asako Takashi, Suzuki Shin, Itami Kenichiro, Muto Kei, Yamaguchi Junichiro

    CHEMISTRY LETTERS   47 ( 8 ) 968 - 970  2018.08  [Refereed]

    DOI

  • Pd-Catalyzed Dearomative Allylation of Benzyl Phosphates

    Komatsuda, Masaaki, Muto Kei, Yamaguchi Junichiro

    Organic Letters   20 ( 14 ) 4354 - 4357  2018.07  [Refereed]

    Authorship:Corresponding author

    DOI

  • Dibenzofuran Synthesis: Decarbonylative Intramolecular C-H Arylation of Aromatic Esters

    Okita Toshimasa, Komatsuda Masaaki, Saito Ami N, Hisada Tomoya, Takahara Tomoaki T, Nakayama Keito P, Isshiki Ryota, Takise Ryosuke, Muto Kei, Yamaguchi Junichiro

    ASIAN JOURNAL OF ORGANIC CHEMISTRY   7 ( 7 ) 1358 - 1361  2018.07  [Refereed]

    DOI

  • Dibenzofuran Synthesis: Decarbonylative Intramolecular C–H Arylation of Aromatic Esters

    Okita, Toshimasa, Komatsuda Masaaki, Saito, Ami N, Hisada Tomoya, Takahara Tomoaki T, Nakayama Keito P, Isshiki Ryota, Takise, Ryosuke, Muto, Kei, Yamaguchi, Junichiro

      7   1358 - 1361  2018.06

    DOI

  • Synthesis of A Heptaarylisoquinoline: Unusual Disconnection for Constructing Isoquinoline Frameworks

    Asako, Takashi, Suzuki, Shin, Itami, Kenichiro, Muto, Kei, Yamaguchi, Junichiro

    Chemistry Letters   47   968 - 970  2018.06

    DOI

  • Decarbonylative Methylation of Aromatic Esters by a Nickel Catalyst

    Toshimasa Okita, Kei Muto, Junichiro Yamaguchi

    Organic Letters   20 ( 10 ) 3132 - 3135  2018.05  [Refereed]

     View Summary

    A Ni-catalyzed decarbonylative methylation of aromatic esters was achieved using methylaluminums as methylating agents. Dimethylaluminum chlorides uniquely worked as the methyl source. Because of the Lewis acidity of aluminum reagents, less reactive alkyl esters could also undergo the present methylation. By controlling the Lewis acidity of aluminum reagents, a chemoselective decarbonylative cross-coupling between alkyl esters and phenyl esters was successful.

    DOI

  • Decarbonylative Methylation of Aromatic Esters by a Nickel Catalyst

    Toshimasa Okita, Kei Muto, Junichiro Yamaguchi

    Organic Letters   20 ( 10 ) 3132 - 3135  2018.05

     View Summary

    A Ni-catalyzed decarbonylative methylation of aromatic esters was achieved using methylaluminums as methylating agents. Dimethylaluminum chlorides uniquely worked as the methyl source. Because of the Lewis acidity of aluminum reagents, less reactive alkyl esters could also undergo the present methylation. By controlling the Lewis acidity of aluminum reagents, a chemoselective decarbonylative cross-coupling between alkyl esters and phenyl esters was successful.

    DOI

  • Pd-Catalyzed Decarbonylative C–H Coupling of Azoles and Aromatic Esters

    Matsushita Kaoru, Takise, Ryosuke, Hisada Tomoya, Suzuki Shin, Isshiki Ryota, Itami Kenichiro, Muto, Kei, Yamaguchi, Junichiro

    Chemistry An Asian Journal   13 ( 17 ) 2393 - 2396  2018.05  [Refereed]

    DOI

  • Decarbonylative C-P bond formation using aromatic esters and organophosphorus compounds

    Ryota Isshiki, Kei Muto, Junichiro Yamaguchi

    Organic Letters   20 ( 4 ) 1150 - 1153  2018.02

     View Summary

    Ni-catalyzed C-P bond formation was achieved using aromatic esters as unconventional aryl sources. The key to success was the use of a thiophene-based diphosphine ligand (dcypt). Several aromatic esters including heteroaromatics can be coupled with phosphine oxides and phosphates, providing aryl phosphorus compounds. The synthetic utility of the method was demonstrated by application of the present protocol to the sequential coupling reactions.

    DOI

  • Synthesis of Fully Arylated (Hetero) arenes by Coupling Reaction

    Asako Takashi, Muto Kei, Yamaguchi Junichiro

    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN   76 ( 2 ) 98 - 110  2018.02  [Refereed]

  • Decarbonylative coupling reaction of aromatic esters

    Ryota Isshiki, Toshimasa Okita, Kei Muto, Junichiro Yamaguchi

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry   76 ( 4 ) 300 - 314  2018  [Refereed]

     View Summary

    Transition metal-catalyzed cross-coupling reactions are a powerful method to form chemical bonds. Conventionally, haloarenes has been used as the most reliable aryl electrophiles in cross- coupling. Recent studies in the cross-coupling arena have enabled to employ unconventional but ubiquitous aryl electrophiles such as phenol and aniline. With this trend of organic synthesis, cross-coupling reactions using aromatic carboxylic acid derivatives such as esters as aryl electrophiles have gained considerable attention as a de novo and efficient method to construct C-C and C-heteroatom bonds. In order to realize this particular transformation, it is important to develop and design transition metal catalysts, those are active toward the scission of ester C-O bonds and decarbonylation. In this review, we describe the progress of catalytic decarbonylative cross- coupling of aromatic esters including chronological aspects and mechanistic considerations.

    DOI

  • Synthesis of fully arylated (hetero) arenes by coupling reaction

    Asako, Takashi, Muto, Kei, Yamaguchi, Junichiro

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry   76 ( 2 ) 98 - 110  2018.01

     View Summary

    Multiply arylated (hetero) arenes are intriguing structural motifs in functional molecules, such as natural products, pharmaceuticals and functional organic materials. In recent decades, many synthesis methods of multiply arylated (hetero) arenes have been reported. As a subclass of multiply arylated arenes, fully arylated (hetero) arenes have also flourished as a unique structural class in functional organic materials and biologically active compounds. Despite the successful application of fully arylated (hetero) arenes with different aryl substituents, the synthesis of such (hetero) arenes has not been explored compared to partially arylated arenes due to the difficulty of synthesizing sterically hindered and highly unsymmetrical aromatic cores. This review reports the synthesis of fully arylated (hetero) arenes bearing more than two different aryl substituents and categorizes this emerging topic by the type of (hetero) arene core, focusing on the methods employing cross-coupling reaction including direct C-H arylation.

    DOI

  • Decarbonylative aryl thioether synthesis by Ni catalysis

    Kota Ishitobi, Ryota Isshiki, Kitty Asahara, Cassandra Lim, Kei Muto, Junichiro Yamaguchi

    Chemistry Letters   47 ( 6 ) 756 - 759  2018  [Refereed]

     View Summary

    A decarbonylative aryl thioether synthesis by nickel catalysis is described. After optimization of the reaction conditions, two air-stable Ni catalytic systems [Ni(OAc)2/PnBu3 and Ni(OAc)2/dppb] were identified. Using these catalysts, various aryl thioesters can be converted to the corresponding aryl thioethers in decarbonylative fashion.

    DOI

  • Decarbonylative coupling reaction of aromatic esters

    Ryota Isshiki, Toshimasa Okita, Kei Muto, Junichiro Yamaguchi

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry   76 ( 4 ) 300 - 314  2018

     View Summary

    Transition metal-catalyzed cross-coupling reactions are a powerful method to form chemical bonds. Conventionally, haloarenes has been used as the most reliable aryl electrophiles in cross- coupling. Recent studies in the cross-coupling arena have enabled to employ unconventional but ubiquitous aryl electrophiles such as phenol and aniline. With this trend of organic synthesis, cross-coupling reactions using aromatic carboxylic acid derivatives such as esters as aryl electrophiles have gained considerable attention as a de novo and efficient method to construct C-C and C-heteroatom bonds. In order to realize this particular transformation, it is important to develop and design transition metal catalysts, those are active toward the scission of ester C-O bonds and decarbonylation. In this review, we describe the progress of catalytic decarbonylative cross- coupling of aromatic esters including chronological aspects and mechanistic considerations.

    DOI

  • Catalytic alpha-Arylation of Ketones with Heteroaromatic Esters

    Ryota Isshiki, Ryosuke Takise, Kenichiro Itami, Kei Muto, Junichiro Yamaguchi

    SYNLETT   28 ( 19 ) 2599 - 2603  2017.12

     View Summary

    Heteroaromatic esters were found to be applicable as an arylating agent for the Pd-catalyzed -arylation of ketones in a decarbonylative fashion. The use of our in-house ligand, dcypt, enabled this unique bond formation. Considering the ubiquity and low cost of aromatic esters, the present work will allow for rapid access to valuable -aryl carbonyl compounds.

    DOI

  • Cross-coupling of aromatic esters and amides

    Ryosuke Takise, Kei Muto, Junichiro Yamaguchi

    CHEMICAL SOCIETY REVIEWS   46 ( 19 ) 5864 - 5888  2017.10

     View Summary

    Catalytic cross-coupling reactions of aromatic esters and amides have recently gained considerable attention from synthetic chemists as de novo and efficient synthetic methods to form C-C and C-heteroatom bonds. Esters and amides can be used as diversifiable groups in metal-catalyzed cross-coupling: in a decarbonylative manner, they can be utilized as leaving groups, whereas in a non-decarbonylative manner, they can form ketone derivatives. In this review, recent advances of this research topic are discussed.

    DOI

  • Synthesis of multiply arylated pyridines

    Takashi Asako, Wakana Hayashi, Kazuma Amaike, Shin Suzuki, Kenichiro Itami, Kei Muto, Junichiro Yamaguchi

    TETRAHEDRON   73 ( 26 ) 3669 - 3676  2017.06

     View Summary

    We have achieved a synthesis of multiply arylated pyridines by using a [4 + 2] cycloaddition of 2,4-diaryl-5-chloroxazoles and cinnamic acids as a key reaction. The resulting hydroxytriarylpyridines can be derivatized into triarylpyridines, tetraarylpyridines and pentaarylpyridines by sequential cross couplings. This synthetic method allows for facile and rapid access to highly arylated pyridines with different aryl substituents. (C) 2017 Elsevier Ltd. All rights reserved.

    DOI

  • Decarbonylative Diaryl Ether Synthesis by Pd and Ni Catalysis

    Ryosuke Takise, Ryota Isshiki, Kei Muto, Kenichiro Itami, Junichiro Yamaguchi

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   139 ( 9 ) 3340 - 3343  2017.03

     View Summary

    Because diaryl ethers are present as an important motif in pharmaceuticals and natural products, extensive studies for the development of novel methods have been conducted. A conventional method for the construction of the diaryl ether moiety is the intermolecular cross-coupling reaction of aryl halides and phenols with a copper or palladium catalyst. We developed a catalytic decarbonylative etherification of aromatic esters using a palladium or nickel catalyst with our enabling diphosphine ligand to give the corresponding diaryl ethers. The present reaction can be conducted on grain scale in excellent yield. This reaction not only functions in an intramolecular setting but also allows for a crossetherification using other phenols.

    DOI

  • Palladium-catalyzed Decarbonylative Alkynylation of Aromatic Esters

    Toshimasa Okita, Kazushi Kumazawa, Ryosuke Takise, Kei Muto, Kenichiro Itami, Junichiro Yamaguchi

    CHEMISTRY LETTERS   46 ( 2 ) 218 - 220  2017.02

     View Summary

    A palladium-catalyzed decarbonylative alkynylation reaction of aromatic esters with terminal alkynes is reported. This reaction allows for halogen-free Sonogashira coupling, resulting in various aryl- and heteroarylalkynes. The utility of the reaction was demonstrated by orthogonal coupling reaction.

    DOI

  • Palladium-Catalyzed Decarbonylative Cross-Coupling of Azinecarboxylates with Arylboronic Acids

    Kei Muto, Taito Hatakeyama, Kenichiro Itami, Junichiro Yamaguchi

    ORGANIC LETTERS   18 ( 19 ) 5106 - 5109  2016.10

     View Summary

    The first palladium-catalyzed decarbonylative coupling of phenyl 2-azinecarboxylates and arylboronic acids is presented. The key for the development of this decarbonylative coupling is the use of Pd/dcype as a catalyst. A wide range of 2-azinecarboxylates can undergo the present coupling reaction to afford 2-arylazines. By combination with previously reported nickel-catalyzed decarbonylative coupling, we achieved a chemoselective sequential decarbonylative coupling of pyridine dicarboxylate to synthesize 2,4-diarylpyridine.

    DOI

  • Nickel-Catalyzed Aromatic C–H Functionalization

    Junichiro Yamaguchi, Kei Muto, Kenichiro Itami

    Topics in Current Chemistry   374 ( 4 ) 55  2016.08

     View Summary

    Catalytic C–H functionalization using transition metals has received significant interest from organic chemists because it provides a new strategy to construct carbon–carbon bonds and carbon–heteroatom bonds in highly functionalized, complex molecules without pre-functionalization. Recently, inexpensive catalysts based on transition metals such as copper, iron, cobalt, and nickel have seen more use in the laboratory. This review describes recent progress in nickel-catalyzed aromatic C–H functionalization reactions classified by reaction types and reaction partners. Furthermore, some reaction mechanisms are described and cutting-edge syntheses of natural products and pharmaceuticals using nickel-catalyzed aromatic C–H functionalization are presented.

    DOI

  • Catalytic Enantioselective Dihalogenation Reaction of Alkene

    Muto Kei

    Journal of Synthetic Organic Chemistry, Japan   74 ( 12 ) 1225 - 1226  2016

     View Summary

    <p>Dihalogenation of alkene is well known reaction undergoing in a stereospecific manner. Although enantioselective dihalogenation of alkene using chiral auxiliary was developed, the catalytic protocol remained as a challenging issue. This review summarizes recent progress of catalytic enantioselective dihalogenation of alkene.</p>

    DOI CiNii

  • Decarbonylative organoboron cross-coupling of esters by nickel catalysis

    Kei Muto, Junichiro Yamaguchi, Djamaladdin G. Musaev, Kenichiro Itami

    NATURE COMMUNICATIONS   6   7508  2015.06

     View Summary

    The Suzuki-Miyaura cross-coupling is a metal-catalysed reaction in which boron-based nucleophiles and halide-based electrophiles are reacted to form a single molecule. This is one of the most reliable tools in synthetic chemistry, and is extensively used in the synthesis of pharmaceuticals, agrochemicals and organic materials. Herein, we report a significant advance in the choice of electrophilic coupling partner in this reaction. With a user-friendly and inexpensive nickel catalyst, a range of phenyl esters of aromatic, heteroaromatic and aliphatic carboxylic acids react with boronic acids in a decarbonylative manner. Overall, phenyl ester moieties function as leaving groups. Theoretical calculations uncovered key mechanistic features of this unusual decarbonylative coupling. Since extraordinary numbers of ester-containing molecules are available both commercially and synthetically, this new 'ester' cross-coupling should find significant use in synthetic chemistry as an alternative to the standard halide-based Suzuki-Miyaura coupling.

    DOI

  • C-H Activation Generates Period-Shortening Molecules That Target Cryptochrome in the Mammalian Circadian Clock

    Tsuyoshi Oshima, Iori Yamanaka, Anupriya Kumar, Junichiro Yamaguchi, Taeko Nishiwaki-Ohkawa, Kei Muto, Rika Kawamura, Tsuyoshi Hirota, Kazuhiro Yagita, Stephan Irle, Steve A. Kay, Takashi Yoshimura, Kenichiro Itami

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   54 ( 24 ) 7193 - 7197  2015.06

     View Summary

    The synthesis and functional analysis of KL001 derivatives, which are modulators of the mammalian circadian clock, are described. By using cutting-edge C-H activation chemistry, a focused library of KL001 derivatives was rapidly constructed, which enabled the identification of the critical sites on KL001 derivatives that induce a rhythm-changing activity along with the components that trigger opposite modes of action. The first period-shortening molecules that target the cryptochrome (CRY) were thus discovered. Detailed studies on the effects of these compounds on CRY stability implicate the existence of an as yet undiscovered regulatory mechanism.

    DOI

  • C-H arylation and alkenylation of imidazoles by nickel catalysis: solvent-accelerated imidazole C-H activation

    Kei Muto, Taito Hatakeyama, Junichiro Yamaguchi, Kenichiro Itami

    CHEMICAL SCIENCE   6 ( 12 ) 6792 - 6798  2015

     View Summary

    The first nickel-catalyzed C-H arylations and alkenylations of imidazoles with phenol and enol derivatives are described. Under the influence of Ni(OTf)(2)/dcype/K3PO4 (dcype: 1,2-bis(dicyclohexylphosphino) ethane) in t-amyl alcohol, imidazoles can undergo C-H arylation with phenol derivatives. The C-H arylation of imidazoles with chloroarenes as well as that of thiazoles and oxazoles with phenol derivatives can also be achieved with this catalytic system. By changing the ligand to dcypt (3,4-bis(dicyclohexylphosphino) thiophene), enol derivatives could also be employed as coupling partners achieving the C-H alkenylation of imidazoles as well as thiazoles and oxazoles. Thus, a range of C2-arylated and alkenylated azoles can be synthesized using this newly developed nickel-based catalytic system. The key to the success of the C-H coupling of imidazoles is the use of a tertiary alcohol as solvent. This also allows the use of an air-stable nickel(II) salt as the catalyst precursor.

    DOI

  • Key mechanistic features of Ni-catalyzed C-H/C-O biaryl coupling of azoles and naphthalen-2-yl pivalates

    Huiying Xu, Kei Muto, Junichiro Yamaguchi, Cunyuan Zhao, Kenichiro Itami, Djamaladdin G. Musaev

    Journal of the American Chemical Society   136 ( 42 ) 14834 - 14844  2014.10

     View Summary

    The mechanism of the Ni-dcype-catalyzed C-H/C-O coupling of benzoxazole and naphthalen-2-yl pivalate was studied. Special attention was devoted to the base effect in the C-O oxidative addition and C-H activation steps as well as the C-H substrate effect in the C-H activation step. No base effect in the C(aryl)-O oxidative addition to Ni-dcype was found, but the nature of the base and C-H substrate plays a crucial role in the following C-H activation. In the absence of base, the azole C-H activation initiated by the C-O oxidative addition product Ni(dcype)(Naph)(PivO), 1B, proceeds via ΔG = 34.7 kcal/mol barrier. Addition of Cs2CO3 base to the reaction mixture forms the Ni(dcype)(Naph)[PivOCs·CsCO3], 3-Cs-clus, cluster complex rather than undergoing PivO- → CsCO3- ligand exchange. Coordination of azole to the resulting 3-Cs-clus complex forms intermediate with a weak Cs-heteroatom(azole) bond, the existence of which increases acidity of the activated C-H bond and reduces C-H activation barrier. This conclusion from computation is consistent with experiments showing that the addition of Cs2CO3 to the reaction mixture of 1B and benzoxazole increases yield of C-H/C-O coupling from 32% to 67% and makes the reaction faster by 3-fold. This emerging mechanistic knowledge was validated by further exploring base and C-H substrate effects via replacing Cs2CO3 with K2CO3 and benzoxazole (1a) with 1H-benzo[d]imidazole (1b) or quinazoline (1c). We proposed the modified catalytic cycle for the Ni(cod)(dcype)-catalyzed C-H/C-O coupling of benzoxazole and naphthalen-2-yl pivalate. (Chemical Equation Presented)

    DOI PubMed

  • Nickel-Catalyzed alpha-Arylation of Ketones with Phenol Derivatives

    Ryosuke Takise, Kei Muto, Junichiro Yamaguchi, Kenichiro Itami

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   53 ( 26 ) 6791 - 6794  2014.06

     View Summary

    The nickel-catalyzed alpha-arylation of ketones with readily available phenol derivatives (esters and carbamates) provides access to useful alpha-arylketones. For this transformation, 3,4-bis(dicyclohexylphosphino)thiophene (dcypt) was identified as a new, enabling, air-stable ligand for this transformation. The intermediate of an assumed C-O oxidative addition was isolated and characterized by X-ray crystal-structure analysis.

    DOI

  • Isolation, structure, and reactivity of an arylnickel(II) pivalate complex in catalytic C-H/C-O biaryl coupling

    Kei Muto, Junichiro Yamaguchi, Aiwen Lei, Kenichiro Itami

    Journal of the American Chemical Society   135 ( 44 ) 16384 - 16387  2013.11

     View Summary

    We describe mechanistic studies of a C-H/C-O biaryl coupling of 1,3-azoles and aryl pivalates catalyzed by Ni(cod)2/dcype. This study not only supports a catalytic cycle consisting of C-O oxidative addition, C-H nickelation, and reductive elimination but also provides insight into the dramatic ligand effect in C-H/C-O coupling. We have achieved the first synthesis, isolation and structure elucidation of an arylnickel(II) pivalate, which is an intermediate in the catalytic cycle after oxidative addition of a C-O bond. Furthermore, kinetic studies and kinetic isotope effect investigations reveal that the C-H nickelation is the turnover-limiting step in the catalytic cycle. © 2013 American Chemical Society.

    DOI PubMed

  • C-H Alkenylation of Azoles with Enols and Esters by Nickel Catalysis

    Lingkui Meng, Yuko Kamada, Kei Muto, Junichiro Yamaguchi, Kenichiro Itami

    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   52 ( 38 ) 10048 - 10051  2013.09

    DOI

  • Recent Progress in Nickel-Catalyzed Biaryl Coupling

    Junichiro Yamaguchi, Kei Muto, Kenichiro Itami

    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY   ( 1 ) 19 - 30  2013.01

     View Summary

    Nickel catalysis for biaryl coupling reactions has received significant attention as a less expensive and less toxic alternative to "standard" palladium catalysis. Here we describe recent developments in nickel-catalyzed biaryl coupling methodology, along with mechanistic studies and applications. In particular we focus on nickel-catalyzed coupling reactions in which "unreactive" bonds such as C-H, C-O, and C-C bonds are converted into biaryl moieties.

    DOI

  • Nickel-catalyzed direct coupling of heteroarenes

    Junichiro Yamaguchi, Kei Muto, Kazuma Amaike, Takuya Yamamoto, Kenichiro Itami

    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry   71 ( 6 ) 576 - 587  2013

     View Summary

    Nickel-catalyzed cross-coupling reactions have recently been receiving significant attention from the synthetic community as a way to construct carbon-carbon or carbon-heteroatom bonds, because nickel catalysts are less expensive and less toxic than palladium catalysts. We herein describe our recent developments in nickel-catalyzed biaryl coupling methodology, along with mechanistic studies and applications to the synthesis of natural products and pharmaceuticals. In particular, we focus on nickel-catalyzed direct coupling reactions in which "unreactive" bonds such as C-H, C-O, and C-C bonds are converted into biaryl moieties.

    DOI

  • Decarbonylative C-H Coupling of Azoles and Aryl Esters: Unprecedented Nickel Catalysis and Application to the Synthesis of Muscoride A

    Kazuma Amaike, Kei Muto, Junichiro Yamaguchi, Kenichiro Itami

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   134 ( 33 ) 13573 - 13576  2012.08

     View Summary

    A nickel-catalyzed decarbonylative C-H biaryl coupling of azoles and aryl esters is described. The newly developed catalytic system does not require the use of expensive metal catalysts or silver- or copper-based stoichiometric oxidants. We have successfully applied this new C-H arylation reaction to a convergent formal synthesis of muscoride A.

    DOI

  • Nickel-Catalyzed C-H/C-O Coupling of Azoles with Phenol Derivatives

    Kei Muto, Junichiro Yamaguchi, Kenichiro Itami

    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   134 ( 1 ) 169 - 172  2012.01

     View Summary

    The first nickel-catalyzed C-H bond arylation of azoles with phenol derivatives is described. The new Ni(cod)(2)/dcype catalytic system is active for the coupling of various phenol derivatives such as esters, carbamates, carbonates, sulfamates, triflates, tosylates, and mesylates. With this C-H/C-O biaryl coupling, we synthesized a series of privileged 2-arylazoles, including biologically active alkaloids. Moreover, we demonstrated the utility of the present reaction for functionalizing estrone and quinine.

    DOI

  • Nickel-Catalyzed C-H Arylation of Azoles with Haloarenes: Scope, Mechanism, and Applications to the Synthesis of Bioactive Molecules

    Takuya Yamamoto, Kei Muto, Masato Komiyama, Jerome Canivet, Junichiro Yamaguchi, Kenichiro Itami

    CHEMISTRY-A EUROPEAN JOURNAL   17 ( 36 ) 10113 - 10122  2011.08

     View Summary

    Novel nickel-based catalytic systems for the C-H arylation of azoles with haloarenes and aryl triflates have been developed. We have established that Ni(OAc)(2)/bipy/LiOtBu serves as a general catalytic system for the coupling with aryl bromides and iodides as aryl electrophiles. For couplings with more challenging electrophiles, such as aryl chlorides and triflates, the Ni(OAc)(2)/dppf (dppf = 1,1'-bis(diphenylphosphino)ferrocene) system was found to be effective. Thiazoles, benzothiazoles, oxazoles, benzoxazoles, and benzimidazoles can be used as the heteroarene coupling partner. Upon further investigation, we discovered a new protocol for the present coupling using Mg(OtBu)(2) as a milder and less expensive alternative to LiOtBu. Attempts to reveal the mechanism of this nickel-catalyzed heterobiaryl coupling are also described. This newly developed methodology has been successfully applied to the syntheses of febuxostat (a xanthine oxidase inhibitor that is effective for the treatment of gout and hyperuricemia), tafamidis (effective for the treatment of TTR amyloid polyneuropathy), and texaline (a natural product having antitubercular activity).

    DOI

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Books and Other Publications

  • New Cross-coupling Reactions through Nickel Catalysis

    Junichiro Yamaguchi, Kazuma Amaike, Kei Muto, Kenichiro Itami

Misc

  • Nickel-Catalyzed Aromatic C-H Functionalization

    Junichiro Yamaguchi, Kei Muto, Kenichiro Itami

    TOPICS IN CURRENT CHEMISTRY   374 ( 4 )  2016.08

    Book review, literature introduction, etc.  

     View Summary

    Catalytic C-H functionalization using transition metals has received significant interest from organic chemists because it provides a new strategy to construct carbon-carbon bonds and carbon-heteroatom bonds in highly functionalized, complex molecules without pre-functionalization. Recently, inexpensive catalysts based on transition metals such as copper, iron, cobalt, and nickel have seen more use in the laboratory. This review describes recent progress in nickelcatalyzed aromatic C-H functionalization reactions classified by reaction types and reaction partners. Furthermore, some reaction mechanisms are described and cutting-edge syntheses of natural products and pharmaceuticals using nickel-catalyzed aromatic C-H functionalization are presented.

    DOI

Awards

  • Special Lecture for Young Scientist

    2022.03   Chemical Society Japan  

  • 研究企画賞 (中外製薬)

    2020.12   有機合成化学協会   ベンジルパラジウム錯体を中間体とするハロアレーンのカルボアミノ化反応の開発

  • Reaxys PhD Prize Finalist

    2016.06   Elsevier  

  • JSPS Ikushi Prize

    2016.03   JSPS  

  • Nagoya University Outstanding Graduate Student Award

    2015.06   Nagoya University  

  • 94th CSJ Oral Student Presentation Award

    2014.03   Chemical Society of Japan  

  • 2013 IGER Nagoya University Annual Research Award

    2014.01   Nagoya University  

  • Otsu Academy Fellow

    2013.10   MSD Life Science Foundation, Public Interest Incorporated Foudnation  

  • Award for Outstanding Master Studenct

    2013.03   Nagoya University  

  • Poster Award on 59th Symposium of Organometallics

    2012.10   Kinki Chemical Society  

  • Poster Award on 29h seminar of synthetic organic chemistry Japan

    2012.09   The Society of Synthetic Organic Chemistry, Japan  

  • Poster Award on 100th symposium of synthetic organic chemistry Japan

    2011.11   The Society of Synthetic Organic Chemistry, Japan  

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Research Projects

  • ベンジルパラジウムの遠隔位結合形成能を活用する芳香環の三成分連結型変換

    日本学術振興会  科学研究費助成事業 基盤研究(C)

    Project Year :

    2021.04
    -
    2024.03
     

    武藤 慶

  • Development of Dearomative Alkylation using Hybrid Catalysis

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Project Year :

    2020.04
    -
    2022.03
     

  • 配位子による反応空間制御を鍵とする触媒的脱芳香族的官能基化反応の開発と応用

    日本学術振興会  科学研究費助成事業 若手研究

    Project Year :

    2019.04
    -
    2021.03
     

    武藤 慶

     View Summary

    多置換脂環式分子のモジュラー合成法の確立を志向し、ユビキタスなアレーンの脱芳香族的官能基化反応の開発を行った。脱芳香族的官能基化はいくつか既に知られるものの、その反応の効率は出発原料の芳香族の電子的性質に強く依存する。電子的な偏りの小さいベンゼノイドの効率的な手法はごく小数例しかなく、過剰量のアレーンを用いるという決定的な課題を抱える。我々は、これまでの研究においてベンジルアルコールの触媒的脱芳香族的C-C結合形成法の開発に成功した。しかし、生成物が不安定であり、本手法を多置換脂環式分子合成へと展開することが難しい状況であった。
    そこで、本研究では脱芳香族的反応後の誘導化を見据え、生成物の安定性と誘導容易性を獲得すべく、芳香族シアノヒドリンの脱芳香族的官能基化の開発をした。この反応で得られる生成物はα,β不飽和ニトリル部位をもつ。本研究の申請段階で、パラジウムと一般的なトリアリールホスフィンを触媒とすると、目的とする芳香族シアノヒドリンとアリル求核剤との脱芳香族的アリル化が進行することはわかっていた。しかし、望まぬ副反応としてベンジル置換反応がかなりの割合で生じることが課題となっていた。今年度の研究により、アリールホスフィンのメタ位に嵩高い置換基を導入することで劇的な化学選択性が誘起できることがわかり、副反応を抑制できることを見いだした。生成物の誘導化も予期したとおり多岐にわたり、多置換脂環式化合物の合成法を確立できた。具体的には、炭素求核剤の共役付加やニトリルや生成物上のアルケンの還元など、様々な誘導化を実施できた。

  • Dearomative functionalization using hybrid catalysis

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

    Project Year :

    2018.04
    -
    2020.03
     

  • Development of dearomative reaction controlled by directing leaving group

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Project Year :

    2017.04
    -
    2019.03
     

    MUTO Kei, Komatsuda Masaaki, Kayashima Yuki, Yanagimoto Aika, Yamaguchi Junichiro

     View Summary

    We developed a Pd-catalyzed dearomative allylation of benzylphosphates as well as carbonates. Of note, this reaction can proceed by using aromatic substrates as a limiting reagent in a catalytic manner. The use of electron-rich triarylphosphine as a ligand accelerates reaction. We succeeded in the derivatization of dearomative products to synthesize valuable acyclic building block.
    Moreover, based upon this work, we also discovered dearomative allylations of other benzyl substrates.

  • π-ベンジル錯体を鍵中間体とするベンゼン環の脱芳香族的官能基化反応の開発

    日本学術振興会  科学研究費助成事業 研究活動スタート支援

    Project Year :

    2016.08
    -
    2018.03
     

    武藤 慶

     View Summary

    ベンゼン環は有機分子における最頻出骨格であり剛直な平面構造をもつ。さらに芳香族安定化効果により種々の有機反応に対し安定である。芳香族求電子置換反応や触媒的クロスカップリング反応の進展により、芳香環の水平方向への化学修飾が容易になってきている。しかし、芳香環の垂直方向への化学修飾、すなわち脱芳香族的官能基化反応の開発は未だ報告例が限られる。このような脱芳香族的変換反応の実現は、ユビキタス骨格であるベンゼン環から三次元骨格をもつ分子の新規合成法となるため、有機合成化学の力量を押し上げることが期待できる。これまでに知られる脱芳香族的反応では、Birch還元や遷移金属触媒を用いた水素化が知られるが、これらの手法では芳香族性を壊しながら炭素置換基を導入することはできない。置換基の導入を伴う反応としては、主にフェノールやインドールなどの電子豊富芳香環に限られ、それ以外の芳香族分子に対する当該手法は少ない。本研究では、変換困難な芳香族分子群に対し芳香環上の置換基切断を起点する戦略に基づき触媒的脱芳香族的官能基化の開発を行った。
    具体的にはベンジルアルコール類と有機スズを化合物との脱芳香族的官能基化の開発をおこなった。ベンジルアルコール類は天然に豊富に存在する安価で低毒性な分子群であり、多くの有機分子骨格にみられる。ベンジルアルコール類の脱芳香族的官能基化を実現するにあたり、遷移金属触媒を用いてベンジル位C-O結合の切断を起点とする戦略に着目した。一般にC-O結合は反応性が低く、この結合切断を促進する触媒開発が重要となる。検討の結果、C-O結合の切断と脱芳香族的に置換基導入を可能にする高効率な触媒を見出すに至った。有機スズ化合物以外の求核剤が反応することも明らかになった。以上のことから研究は当初の期待以上に進展した。

  • ニッケル触媒を用いた炭素-水素結合直接変換反応の開発と応用

    日本学術振興会  科学研究費助成事業 特別研究員奨励費

    Project Year :

    2013.04
    -
    2016.03
     

    武藤 慶

     View Summary

    遷移金属触媒を用いた芳香環連結反応は、最も進展が著しい有機合成分野の一つである。従来、鈴木宮浦カップリング反応などの、パラジウム触媒を用いたアリール金属種とハロゲン化アリールとのクロスカップリングがビアリール合成のスタンダードとして頻用されてきた。近年ではこの従来法が抱える、多段階プロセス問題、ハロゲン問題、そして高価な金属触媒の使用といった問題点の解決に向けた、より理想的な方法論の開拓研究が注目されている。
    本研究では、上記の課題を解決すべく、1)調製に多段階を要するアリール金属種に代わり、その原料である芳香環を直接反応させる、2)ハロゲン化アリールに代わりハロゲンを含まないフェノール誘導体をカップリング剤に用いる、3)高価なパラジウム触媒に代わり、安価なニッケルを金属触媒に用いる、といった3つを同時に満たす新規クロスカップリング反応の開発研究を行った。
    その結果、新たなニッケル触媒を用いることで、オキサゾールやチアゾールのC-H結合とフェノール誘導体のC-O結合を切断し、連結させるC-H/C-Oカップリングの開発に成功した。
    反応開発にとどまらず、様々な生物活性物質の迅速合成へと応用展開することができた。さらに、反応中間体の単離、速度論実験などの実験化学と、量子化学計算が連動した機構解明研究を行い、触媒サイクルと新たなニッケル触媒の反応性を明らかにすることにも成功した。
    これらの研究で得た機構的知見をもとに、反応条件の再検討へとフィードバックすることで、エノール誘導体を用いたアゾールの直接アルケニル化や、イミダゾールとフェノール誘導体とのC-H/C-Oカップリング反応の開発へと展開することができた。

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Presentations

  • ベンジルパラジウムを鍵とする不活性芳香族の脱芳香族的官能基化

    武藤慶  [Invited]

    日本化学会 第102春季年会 

    Presentation date: 2022.03

    Event date:
    2022.03
     
     
  • 触媒的結合切断を起点とする新奇分子変換: 芳香環交換反応と脱芳香族的官能基化

    武藤慶  [Invited]

    ハイブリッド触媒 若手道場 

    Presentation date: 2022.02

  • Organic Synthesis by Breaking Arenes: Development of Catalytic Dearomative Functionalization

    Kei Muto, Hiroki Kato, Aika Yanagimoto, Yota Uwabe, Qikun Wu, Itsuki Musha, Masaaki Komatsuda, Junichiro Yamaguchi

    13th AFMC International Medicinal Chemistry Symposium (AIMECS2021) 

    Presentation date: 2021.12

    Event date:
    2021.11
    -
    2021.12
  • ベンジルパラジウム種を活かした触媒的脱芳香族的官能基化反応

    武藤慶  [Invited]

    第48回オルガノメタリックセミナー「効率的分子変換のフロンティア」 

    Presentation date: 2021.11

  • ベンジルパラジウムを経由するブロモアレーンの触媒的脱芳香族的官能基化

    武藤慶, 加藤弘基, 柳本愛華, 上部耀大, ウチクン 武者樹, 小松田雅晃, 山口潤一郎

    第67回有機金属化学討論会 

    Presentation date: 2021.09

  • Organic Synthesis by Breaking Arenes: Development of Catalytic Dearomative Functionalization

    Kei Muto  [Invited]

    Reaxys PhD Prize Virtual Symposium 

    Presentation date: 2020.10

  • 壊すことで分子をつくる:脱芳香族的合成法の開発

    武藤慶

    令和元年度 日本学術振興会育志賞研究発表会 

    Presentation date: 2020.03

  • Catalyst Design toward Selective Dearomative Functionalizations

    Kei Muto  [Invited]

    The Chemical Society of Japan 2019, 99th Annual Meeting-Special Program Lecture 

    Presentation date: 2019.03

  • C–O結合切断を起点とする新奇触媒反応の開発

    武藤慶  [Invited]

    第二回産総研化学研究シンポジウム 

    Presentation date: 2018.10

  • 分子触媒による新奇分子連結反応の開発

    武藤慶

    平成29年度育志賞研究発表会 

    Presentation date: 2017.09

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Specific Research

  • 汎用芳香族分子の新規三成分連結型二官能基化反応

    2021  

     View Summary

    ヘテロ原子官能基化された芳香族分子は機能の宝庫である。ヘテロ原子の導入により極性、電子的性質は変化する。特に、パラ位二置換芳香族分子は電子的性質や溶解性などの固体物性に劇的な変化を与えるため、医農薬や機能性有機材料分子に頻繁に導入される。本研究では、これら分子への簡便なアクセスを可能にすべく、ハロアレーンやフェノール類などの汎用芳香族分子の位置選択的な1,4-二官能基化反応の開発を目指した。その結果、パラジウム触媒による汎用芳香族分子に対するジアゾ化合物とアミンの1,4-カルボアミノ化が進行することを見いだした。また、分子内に窒素求核部位をもつハロアレーンでは分子内アザスピロ環化することも見いだした。

  • 脱芳香族化を鍵とする迅速なヘテロ脂環式骨格形成法の開発研究

    2020  

     View Summary

    ヘテロ原子をもつ脂環式化合物(ヘテロ脂環式化合物)は医薬品や生理活性物質に見られる重要骨格である。多様な置換様式をもつこれら化合物の新規合成法の開発は合成化学のみならず創薬化学など多分野に大きなインパクトを与える。本研究では、ヘテロ芳香環の脱芳香族的官能基化を開発を目指した。ヘテロ芳香環は豊富な化学フィードストックであり、ヘテロ脂環式分子合成にこれらの使用が可能となれば迅速に多様なヘテロ脂環式分子が合成できる。種々検討の結果、ブロモヘテロ芳香環を脱芳香族的官能基化できる触媒条件を見いだした。パラジウム触媒とジアゾ化合物、種々のカルボニル化合物を用いると、ブロモヘテロ芳香環が効率的に脱芳香族化できた。

  • 炭素-窒素結合切断を起点とする脱芳香族的官能基化反応の開発

    2018  

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    多置換脂環式化合物は豊かな3次元骨格をもつため、創薬研究で需要の高い骨格である。本研究では、そのような脂環式化合物合成の新手法として、ベンジルアミン類を出発物質とし、脱芳香族的官能基化を鍵反応とする合成法の確立を目指した。ベンジルアミンのアミノメチル基は種々の芳香環修飾反応におけるよい配向基として機能するため、位置選択的な化学修飾が可能である。この利点を生かして置換様式の定まったベンジルアミン類を脱芳香族的に官能基化できれば、ベンジルアミン類をテンプレートしてモジュラー式の多置換脂環式化合物合成法となると考えた。そこで、これまでに見いだしたベンジルアルコールのC-O結合切断を起点とする触媒的脱芳香族的アリル化反応を参考に、ベンジルアミン類のC-N結合切断を伴う手法の開発を行った。反応条件を探索した結果、ベンジルアンモニウムとアリルスズとの脱芳香族的アリル化を進行させる触媒的条件を見いだした。ベンジルアミン類の位置選択的化学修飾、続く本脱芳香族的アリル化を用いて、実際に立ち感脂環式化合物合成法の確立も行った。

  • 精密制御分子触媒を用いたフェノールの炭素-ヒドロキシ結合のアミノ化反応

    2016  

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    遷移金属触媒を用いたハロゲン化アリールと有機金属化合物とのクロスカップリング反応は信頼性の高い分子連結反応である。しかし、アリール化剤にハロゲン化アリールを用いなければならないという制約がある。この制約の解決にむけフェノール誘導体やアニリン誘導体を用いたクロスカップリング反応の開発が世界中で行われている。本研究ではフェノールと同様にユビキタス構造体であるカルボン酸誘導体を用いて検討を行い興味深い反応を発見した。具体的に、独自に開発したPd触媒と銅触媒、そしてアミン存在下、芳香族フェニルエステルとアルキンを反応させることで、脱カルボニルを伴いながらアリールアルキンが生成することを見出した。

 

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