研究者データベース

松永 茂樹(マツナガ シゲキ)
薬学研究院 創薬科学部門 創薬化学分野
教授

基本情報

通称等の別名

    北大院薬

所属

  • 薬学研究院 創薬科学部門 創薬化学分野

職名

  • 教授

学位

  • 博士(薬学)(東京大学)

ホームページURL

ORCID ID

J-Global ID

プロフィール

  • 2001.4 東京大学大学院薬学系研究科 助手

    2007.4 東京大学大学院薬学系研究科 助教

    2008.4 東京大学大学院薬学系研究科 講師

    2011.4 東京大学大学院薬学系研究科 准教授

    2015.4 北海道大学大学院薬学研究院 教授

研究キーワード

  • セラノスティクス   C-H官能基化   不斉触媒   不斉合成   シッフ塩基   医薬合成   触媒   イミン   医薬リード   医薬品合成   複核錯体   マンニッヒ反応   希土類金属   アート錯体   非天然アミノ酸   天然物合成   分子活性化   協奏機能   サレン   直截変換   活性エステル   亜鉛触媒   有機合成反応   希土類触媒   ビナフトール   ニトロアルカン   ピロール   医薬化学   多点制御   アルドール反応   不斉アルドール反応   触媒的不斉Strecker反応   

研究分野

  • ライフサイエンス / 薬系化学、創薬科学
  • ナノテク・材料 / 有機合成化学

職歴

  • 2021年07月 - 現在 Angew Chem Int Ed International Advisory Board
  • 2015年04月 - 現在 北海道大学 大学院薬学研究院 教授
  • 2011年04月 - 2015年03月 東京大学 薬学研究科(研究院) 准教授
  • 2008年04月 - 2011年03月 東京大学 大学院薬学系研究科 専任講師
  • 2001年04月 - 2008年03月 東京大学 大学院薬学系研究科 助手、助教

学歴

  • 2000年04月 - 2001年03月   東京大学大学院薬学系研究科博士後期課程
  • 1998年04月 - 2000年03月   東京大学大学院薬学系研究科修士課程
  • 1996年04月 - 1998年03月   東京大学薬学部薬学科
  • 1994年04月 - 1996年03月   東京大学   理科I類

所属学協会

  • 有機合成化学協会   日本希土類学会   アメリカ化学会   日本プロセス化学会   日本化学会   日本薬学会   

研究活動情報

論文

  • Yunhui Feng, Hang Luo, Wanyao Zheng, Shigeki Matsunaga, Luqing Lin
    ACS Catalysis 2022年09月16日 [査読有り]
  • Shota Arai, Koichi Fujiwara, Masahiro Kojima, Haruka Aoki-Saito, Masakiyo Yatomi, Tsugumichi Saito, Yasuhiko Koga, Hayato Fukuda, Mizuki Watanabe, Shigeki Matsunaga, Takeshi Hisada, Satoshi Shuto
    The Journal of Organic Chemistry 87 15 10501 - 10508 2022年08月05日 [査読有り]
  • Yuki Hirata, Daichi Sekine, Yoshimi Kato, Luqing Lin, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Angewandte Chemie International Edition 2022年05月19日 [査読有り][通常論文]
  • Takumaru Kurihara, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Journal of the American Chemical Society 2022年04月27日 [査読有り][通常論文]
  • Yuto Yamaguchi, Yusuke Seino, Akihiko Suzuki, Yuji Kamei, Tatsuhiko Yoshino, Masahiro Kojima, Shigeki Matsunaga
    Organic Letters 24 12 2441 - 2445 2022年04月01日 [査読有り]
  • Kentaro Kawai, Kazuki Ikeda, Akane Sato, Akira Kabasawa, Masahiro Kojima, Kenta Kokado, Akira Kakugo, Kazuki Sada, Tatsuhiko Yoshino, Shigeki Matsunaga
    Journal of the American Chemical Society 144 3 1370 - 1379 2022年01月26日 [査読有り][通常論文]
     
    Dynamic covalent bonds are useful tools in a wide range of applications. Although various reversible chemical reactions have been studied for this purpose, the requirement for harsh conditions, such as high temperature and low or high pH, to activate generally stable covalent bonds limits their potential applications involving biomolecules or household utilization. Here, we report the design, synthesis, characterization, and dynamic covalent bonding properties of 1,2-disubstituted 1,2-dihydro-1,2,4,5-tetrazine-3,6-dione (TETRAD). Hetero-Diels–Alder reactions of TETRAD with furan derivatives and their retro-reactions proceeded rapidly at room temperature under neutral conditions, enabling a chemically induced sol–gel transition system.
  • Tomoyuki Sekino, Shunta Sato, Tatsuhiko Yoshino, Masahiro Kojima, Shigeki Matsunaga
    Organic Letters 2022年 [査読有り][通常論文]
     
    Despite the rapid progress in C-C bond-forming reactions using Katritzky salts, their deaminative allylation remains a challenge. Inspired by the metallaphotoredox-catalyzed allylic substitution regime, here, we report the deaminative allylation of Katritzky salts via cobalt/organophotoredox dual catalysis. This cross-electrophile coupling enables regioselective allylation using a variety of allylic esters, overcoming the substrate limitations of reported protocols. Mechanistic studies indicate the involvement of a π-allyl cobalt complex as a radicalophile that mediates C-C bond formation.
  • Ryo Tanaka, Yuki Hirata, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Chemical Communications 58 1 76 - 79 2022年 [査読有り][通常論文]
     
    The C–H bond addition reaction of 2-phenylpyridine derivatives with α,β-unsaturated carboxylic acids catalyzed by Cp*Rh(iii)/BH3·SMe2 is reported.
  • Jumpei Hirose, Takumi Wakikawa, Shun Satake, Masahiro Kojima, Manabu Hatano, Kazuaki Ishihara, Tatsuhiko Yoshino, Shigeki Matsunaga
    ACS Catalysis 11 24 15187 - 15193 2021年12月07日 [査読有り]
     
    The enantioselective intramolecular oxyamination of unsaturated alkoxyamines using a hybrid catalytic system consisting of Cp*RhIII/chiral disulfonate/CuOAc is described. Tetrahydrofuran derivatives with a tetrasubstituted chiral center were obtained under the optimized conditions in 91:9–97:3 er. The use of a sterically hindered chiral disulfonate and a Cu additive was essential for the high enantioselectivity.
  • Tatsuhiko Yoshino, Shigeki Matsunaga, Long-Tao Huang, Yuki Hirata, Yoshimi Kato, Luqing Lin, Masahiro Kojima
    Synthesis 2021年08月16日 [査読有り]
     
    AbstractRuthenium(II)-catalyzed enantioselective C–H functionalization reactions of sulfoximines with sulfoxonium ylides are described. The combination of [RuCl2(p-cymene)]2 and a pseudo-C 2-symmetric binaphthyl monocarboxylic acid furnished the S-chiral products in 76:24 to 92:8 er.
  • Tatsuhiko Yoshino, Shigeki Matsunaga
    ACS Catalysis 11 11 6455 - 6466 2021年06月04日 [査読有り]
  • Keitaro Matsuoka, Honoka Obata, Kotaro Nagatsu, Masahiro Kojima, Tatsuhiko Yoshino, Mikako Ogawa, Shigeki Matsunaga
    Organic & Biomolecular Chemistry 19 25 5525 - 5528 2021年06月 [査読有り]
     

    The transition-metal-free nucleophilic 211At-astatination of aryliodonium ylides, involving those derived from multi-functionalized molecules and heteroarenes, proceeded with good to excellent radiochemical yields.

  • Yoshimi Kato, Luqing Lin, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    ACS Catalysis 11 7 4271 - 4277 2021年04月02日 [査読有り]
  • Youka Bunno, Yuta Tsukimawashi, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    ACS Catalysis 11 5 2663 - 2668 2021年03月05日 [査読有り]
  • Yuji Kamei, Yusuke Seino, Yuto Yamaguchi, Tatsuhiko Yoshino, Satoshi Maeda, Masahiro Kojima, Shigeki Matsunaga
    Nature Communications 12 1 2021年02月 [査読有り]
     
    AbstractHydrogen atom transfer (HAT) hydrogenation has recently emerged as an indispensable method for the chemoselective reduction of unactivated alkenes. However, the hitherto reported systems basically require stoichiometric amounts of silanes and peroxides, which prevents wider applications, especially with respect to sustainability and safety concerns. Herein, we report a silane- and peroxide-free HAT hydrogenation using a combined cobalt/photoredox catalysis and ascorbic acid (vitamin C) as a sole stoichiometric reactant. A cobalt salophen complex is identified as the optimal cocatalyst for this environmentally benign HAT hydrogenation in aqueous media, which exhibits high functional-group tolerance. In addition to its applicability in the late-stage hydrogenation of amino-acid derivatives and drug molecules, this method offers unique advantage in direct transformation of unprotected sugar derivatives and allows the HAT hydrogenation of unprotected C-glycoside in higher yield compared to previously reported HAT hydrogenation protocols. The proposed mechanism is supported by experimental and theoretical studies.
  • Keitaro Matsuoka, Narumi Komami, Masahiro Kojima, Tsuyoshi Mita, Kimichi Suzuki, Satoshi Maeda, Tatsuhiko Yoshino, Shigeki Matsunaga
    Journal of the American Chemical Society 143 1 103 - 108 2021年01月13日 [査読有り]
     
    Organosilanes are synthetically useful reagents and precursors in organic chemistry. However, the typical inertness of unactivated Si-C(sp3) bonds under conventional reaction conditions has hampered the application of simple tetraalkylsilanes in organic synthesis. Herein we report the chemoselective cleavage of Si-C(sp3) bonds of unactivated tetraalkylsilanes using iodine tris(trifluoroacetate). The reaction proceeds smoothly under mild conditions (-50 °C to room temperature) and tolerates various polar functional groups, thus enabling subsequent Tamao-Fleming oxidation to provide the corresponding alcohols. NMR experiments and density functional theory calculations on the reaction indicate that the transfer of alkyl groups from Si to the I(III) center and the formation of the Si-O bond proceed concertedly to afford an alkyl-λ3-iodane and silyl trifluoroacetate. The developed method enables the use of unactivated tetraalkylsilanes as highly stable synthetic precursors.
  • Qi Mou, Ruyuan Zhao, Ruihan Niu, Seiya Fukagawa, Taiki Shigeno, Tatsuhiko Yoshino, Shigeki Matsunaga, Bo Sun
    Organic Chemistry Frontiers 8 24 6923 - 6930 2021年 [査読有り]
     
    Enantioselective C-H alkylation of ferrocene carboxamides with diazomalonates using an achiral Cp∗Ir(iii)/chiral carboxylic acid is described. The combination of an achiral Cp∗Ir(iii) complex and a binaphthyl-based chiral carboxylic acid provided planar chiral alkylated ferrocenes in good yields with moderate to good enantioselectivity (up to 94 : 6 er). This journal is
  • Ayako Nakano, Yukino Okabe, Keitaro Matsuoka, Narumi Komami, Keito Watanabe, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    HETEROCYCLES 103 2 670 - 670 2021年01月 [査読有り][通常論文]
     
    Monoaryl-lambda(3)-iodanes serve as versatile oxidants and arylating reagents in organic synthesis. In addition to the oxidation of iodoarenes, electrophilic aromatic substitution reactions using iodine tricarboxylates have been used for the synthesis of monoaryl-lambda(3)-iodanes. Here, we report that ipso-substitution reactions of aryltrifluoroborates with iodine tris(trifluoroacetate) in DMF or DMA smoothly produced monoaryl-lambda(3)-iodanes, which were readily converted to aryliodonium ylides. We also demonstrated that sequential C-H borylation and the ipso-substitution efficiently introduced the I(III) group under steric control.
  • Long-Tao Huang, Seiya Fukagawa, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Organic Letters 22 21 8256 - 8260 2020年11月06日 [査読有り]
  • Taku Miyazawa, Takuro Suzuki, Yuhei Kumagai, Koji Takizawa, Takashi Kikuchi, Shunsuke Kato, Akira Onoda, Takashi Hayashi, Yuji Kamei, Futa Kamiyama, Masahiro Anada, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Nature Catalysis 3 10 851 - 858 2020年10月 [査読有り]
     
    The development of robust and reactive chiral catalysts is a fundamental aim in asymmetric catalysis, and crucial for providing efficient methods for synthesizing chiral molecules. Chiral paddle-wheel bimetallic complexes provide a highly tunable chiral environment in rhodium-catalysed asymmetric carbene/nitrene transfer reactions and Lewis acid-catalysed reactions. Chiral paddle-wheel complexes having other transition metals as the reactive metal centre, however, have not yet been identified in asymmetric catalysis. Here, we report the synthesis, structures and high catalytic performances of chiral paddle-wheel diruthenium complexes. The cationic chiral diruthenium complex [Ru2((S)-BPTPI)4]+ exhibited remarkable reactivity as a Lewis acid catalyst for asymmetric hetero-Diels–Alder reactions, achieving a turnover number of up to 1,880,000 with high enantioselectivity (>90% e.e.). The chiral diruthenium complexes also exhibited good reactivity and high enantioselectivity in C–H amination and cyclopropanation reactions under oxidizing conditions, indicating their high tolerance towards oxidation. Our results reveal the chiral paddle-wheel diruthenium scaffold as a promising platform for asymmetric catalysis. [Figure not available: see fulltext.].
  • Tomoyuki Sekino, Shunta Sato, Kazuki Kuwabara, Koji Takizawa, Tatsuhiko Yoshino, Masahiro Kojima, Shigeki Matsunaga
    Synthesis 52 13 1934 - 1946 2020年07月27日 [査読有り]
     
    Despite their unique potential as rare 1,1-dipole synthons, allyl sulfones are rarely used in target-oriented syntheses, likely due to the lack of a general catalytic method for their branch-selective allylic substitution. Herein, we identified allyl 4-chlorophenyl sulfone as a versatile linchpin for both base-mediated α-derivatization and subsequent cobalt-catalyzed allylic substitution. The sequential transformations allow for highly regioselective access to branched allylic substitution products with a variety of aliphatic side chains. The photoredox-enabled­ ­cobalt catalysis is indispensable for achieving high yields and regioselectivity­ for the desulfonylative substitution in contrast to traditional metal-catalyzed protocols, which lead to inferior outcomes in the corresponding transformations.
  • Eiki Tomita, Kodai Yamada, Yu Shibata, Ken Tanaka, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Angewandte Chemie 132 26 10560 - 10564 2020年06月22日 [査読有り]
  • Eiki Tomita, Kodai Yamada, Yu Shibata, Ken Tanaka, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Angewandte Chemie International Edition 59 26 10474 - 10478 2020年06月22日 [査読有り]
  • Tatsuhiko Yoshino, Shun Satake, Shigeki Matsunaga
    Chemistry – A European Journal 26 33 7346 - 7357 2020年06月10日 [査読有り]
     
    Transition-metal-catalyzed C-H functionalization reactions with Cp*M(III)catalysts (M=Co, Rh, Ir) have found a wide variety of applications in organic synthesis. Albeit the intrinsic difficulties in achieving catalytic stereocontrol using these catalysts due to their lack of additional coordination sites for external chiral ligands and the conformational flexibility of the Cp ligand, catalytic enantioselective C-H functionalization reactions using the Group 9 metal triad with Cp-type ligands have been intensively studied since 2012. In this minireview, the progress in these reactions according to the type of the chiral catalyst used are summarized and discussed. The development of chiral Cp(x)ligands the metal complexes thereof, artificial metalloenzymes, chiral carboxylate-assisted enantioselective C-H activations, enantioselective alkylations assisted by chiral carboxylic acids or chiral sulfonates, and chiral transient directing groups are discussed.
  • Masahiro Kojima, Shigeki Matsunaga
    Trends in Chemistry 2 5 410 - 426 2020年05月 [査読有り]
  • Takumaru Kurihara, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Asian Journal of Organic Chemistry Wiley 2020年03月28日 [査読有り][通常論文]
  • Seiya Fukagawa, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Angewandte Chemie International Edition 58 50 18154 - 18158 Wiley 2019年12月09日 [査読有り][通常論文]
     
    Catalytic enantioselective directed methylene C(sp3 )-H amidation reactions of 8-alkylquinolines using a Cp*RhIII /chiral carboxylic acid (CCA) hybrid catalytic system are described. A binaphthyl-based chiral carboxylic acid efficiently differentiates between the enantiotopic methylene C-H bonds, which leads to the formation of C-N bonds with good enantioselectivity.
  • Seiya Fukagawa, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Angewandte Chemie 131 50 18322 - 18326 Wiley 2019年12月09日 [査読有り][通常論文]
  • Daichi Sekine, Kazuki Ikeda, Seiya Fukagawa, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Organometallics 38 20 3921 - 3926 American Chemical Society ({ACS}) 2019年10月28日 [査読有り][通常論文]
  • Ryo Tanaka, Iku Tanimoto, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    The Journal of Organic Chemistry 84 20 13203 - 13210 American Chemical Society ({ACS}) 2019年10月18日 [査読有り][通常論文]
     
    Cobalt-catalyzed C-H allylation reactions of NH-free benzimidates using vinylcyclopropanes or allyl carbonate are reported. The reactive and relatively unstable imidate groups remain intact during the C-H allylations to afford functionalized imidates without dealcoholizations. The thus obtained allylated imidate was subsequently converted into other heterocyclic structures through a following C-H functionalization reaction, demonstrating the synthetic utility of this method.
  • Ryo Tanaka, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Chemistry Letters 48 1046  2019年09月 [査読有り][通常論文]
  • Koji Takizawa, Tomoyuki Sekino, Shunta Sato, Tatsuhiko Yoshino, Masahiro Kojima, Shigeki Matsunaga
    Angewandte Chemie 131 27 9297 - 9301 Wiley 2019年07月24日 [査読有り][通常論文]
  • Keitaro Matsuoka, Narumi Komami, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Asian Journal of Organic Chemistry 8 7 1107 - 1110 Wiley 2019年07月07日 [査読有り][通常論文]
     
    The synthesis of monoaryl-lambda(3)-iodanes generally requires the oxidation of iodoarenes, but the functional group compatibility is often problematic when using oxidizable substrates such as heteroaromatic compounds. Although electrophilic aromatic substitution or ipso-substitution reactions using iodine tricarboxylates have been studied as an alternative synthetic route to dicarboxyiodoarenes, several common heteroaromatic substrates such as indoles, quinolines, (benzo)furans, and (benzo)thiophenes have not been investigated to date. Here, we report that ipso-substitution reactions of heteroaromatic stannanes using I(OAc)(3) in the presence of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) effectively provide diacetoxyiodoarenes, which can be converted into the corresponding iodonium ylides or be directly used in a one-pot iodoarylation reaction.
  • Tatsuhiko Yoshino, Shigeki Matsunaga
    Synlett 30 12 1384 - 1400 2019年07月 [査読有り][通常論文]
     
    This account describes Cp*Co-III-catalyzed C-H functionalization reactions developed in our group between 2013 and 2018. Cp*Co-III-catalysts not only serve as inexpensive alternatives to Cp*Rh-III catalysts but also exhibit unique reactivity and selectivity in several transformations. In the latter part of this review, we introduce catalytic asymmetric C-H functionalization reactions using achiral Rh-III or Co-III catalysts with chiral disulfonates or carboxylic acids as external chiral sources.
  • Koji Takizawa, Tomoyuki Sekino, Shunta Sato, Tatsuhiko Yoshino, Masahiro Kojima, Shigeki Matsunaga
    Angewandte Chemie International Edition 58 27 9199 - 9203 2019年07月01日 [査読有り][通常論文]
     
    Co-catalyzed allylic substitution reactions have received little attention, arguably because of the lack of any known advantage of Co catalysis over either Rh or Ir catalysis. Described here is a general and regioselective Co-catalyzed allylic alkylation using an in situ catalyst activation by organophotoredox catalysis. This noble-metal-free catalytic system exhibits unprecedentedly high reactivities and regioselectivities for the allylation with an allyl sulfone, for the first time, representing the unique synthetic utility of the Co-catalyzed method compared to the related Rh- and Ir-catalyzed reactions.
  • Yuhei Kumagai, Nanami Murakami, Futa Kamiyama, Ryo Tanaka, Tatsuhiko Yoshino, Masahiro Kojima, Shigeki Matsunaga
    Organic Letters 19 10 3600 - 3605 American Chemical Society ({ACS}) 2019年05月17日 [査読有り][通常論文]
  • Tatsuhiko Yoshino, Shigeki Matsunaga
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 77 4 330 - 340 2019年04月 [査読有り]
     
    Transition metal-catalyzed C-H activation/functionalization reactions are attractive and promising methods in modern organic synthesis. Trivalent rhodium with a pentamethylcyclopenta-dienyl ligand, Cp*Rh-III, is one of the most successful catalysts for directing group-assisted C-H functionalization reactions, exhibiting high reactivity, robustness, and good functional group compatibility. Cobalt is analogous to rhodium in the periodic table, but less expensive and more available than rhodium. In this article, we describe our studies on Cp*Co-III-catalyzed directing group-assisted C-H functionalization reactions. The cobalt catalysts not only enable the same transformations as the rhodium catalysts, but also exhibit unique reactivity and selectivity in several reactions due to the lower electronegativity, smaller size, and harder nature of cobalt compared with those of rhodium.Catalytic asymmetric C-H functionalization using Cp*M-III (M=Co, Rh, Ir) catalysts is highly challenging because additional chiral ligands cannot participate in an enantio-determining step. Although well-designed chiral Cp-x ligands were developed and used for catalytic asymmetric reactions, the synthesis of such chiral Cp-x ligands and complexes is sometimes an obstacle to tuning the catalyst structure for achieving high enantioselectivity. As a different approach for asymmetric reactions, we demonstrated that chiral sulfonates and chiral carboxylic acids hybridized with achiral rhodium and cobalt complexes enable enantioselective C-H functionalization.
  • Narumi Komami, Keitaro Matsuoka, Ayako Nakano, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Chemistry - A European Journal 25 5 1217 - 1220 Wiley 2019年01月24日 [査読有り][通常論文]
     
    Monoaryl-λ3 -iodanes are potentially attractive arylating agents. They are generally synthesized from aryl iodides via oxidation, which can cause functional group incompatibility, especially when polyfunctionalized derivatives are desired. This work describes the direct synthesis of monoaryl-λ3 -iodanes through a chemoselective ipso-substitution reaction of arylgermanes and arylstannanes with iodine tris(trifluoroacetate). The generated iodanes were converted to iodonium ylides or used for further transformations in one pot. The presented method enables the preparation of polyfunctionalized monoaryl-λ3 -iodanes.
  • Seiya Fukagawa, Yoshimi Kato, Ryo Tanaka, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Angewandte Chemie 131 4 1165 - 1169 2019年01月21日 [査読有り][通常論文]
  • Seiya Fukagawa, Yoshimi Kato, Ryo Tanaka, Masahiro Kojima, Tatsuhiko Yoshino, Shigeki Matsunaga
    Angewandte Chemie International Edition 58 4 1153 - 1157 2019年01月21日 [査読有り][通常論文]
     
    Recent advances in Cpx MIII catalysis (M=Co, Rh, Ir) have enabled a variety of enantioselective C(sp2 )-H functionalization reactions, but enantioselective C(sp3 )-H functionalization is still largely unexplored. We describe an asymmetric C(sp3 )-H amidation of thioamides using an achiral CoIII /chiral carboxylic acid hybrid catalytic system, which provides easy and straightforward access to chiral β-amino thiocarbonyl and β-amino carbonyl building blocks with a quaternary carbon stereocenter.
  • Shun Satake, Takumaru Kurihara, Keisuke Nishikawa, Takuya Mochizuki, Manabu Hatano, Kazuaki Ishihara, Tatsuhiko Yoshino, Shigeki Matsunaga
    Nature Catalysis 2 1 94 - 94 Springer Nature 2019年01月03日 [査読有り][通常論文]
  • Iku Tanimoto, Kentaro Kawai, Akane Sato, Tatsuhiko Yoshino, Shigeki Matsunaga
    HETEROCYCLES 99 118 - 125 2019年01月 [査読有り][通常論文]
  • Luqing Lin, Seiya Fukagawa, Daichi Sekine, Eiki Tomita, Tatsuhiko Yoshino, Shigeki Matsunaga
    Angewandte Chemie 130 37 12224 - 12228 Wiley 2018年09月10日 [査読有り][通常論文]
  • Luqing Lin, Seiya Fukagawa, Daichi Sekine, Eiki Tomita, Tatsuhiko Yoshino, Shigeki Matsunaga
    Angewandte Chemie International Edition 57 37 12048 - 12052 Wiley 2018年09月10日 [査読有り][通常論文]
  • Takumaru Kurihara, Shun Satake, Manabu Hatano, Kazuaki Ishihara, Tatsuhiko Yoshino, Shigeki Matsunaga
    Chemistry - An Asian Journal 13 17 2378 - 2381 Wiley 2018年09月04日 [査読有り][通常論文]
  • Takuro Suzuki, Seiya Fukagawa, Tatsuhiko Yoshino, Masahiro Anada, Shigeki Matsunaga
    Heterocycles 97 2 2018年09月 [査読有り][通常論文]
  • Shun Satake, Takumaru Kurihara, Keisuke Nishikawa, Takuya Mochizuki, Manabu Hatano, Kazuaki Ishihara, Tatsuhiko Yoshino, Shigeki Matsunaga
    Nature Catalysis 1 8 585 - 591 Springer Nature 2018年08月 [査読有り][通常論文]
  • Kentaro Kawai, Youka Bunno, Tatsuhiko Yoshino, Shigeki Matsunaga
    Chemistry - A European Journal 24 40 10231 - 10237 Wiley 2018年07月17日 [査読有り][通常論文]
  • Tatsuhiko Yoshino, Shigeki Matsunaga
    Asian Journal of Organic Chemistry 7 7 1193 - 1205 Wiley 2018年07月 [査読有り][通常論文]
     
    C-H functionalization reactions hold great potential for the streamlined synthesis of complex molecules and are currently a hot topic in organic synthesis. Among the various transition metals that have been used, cobalt has recently attracted increased attention as a catalyst for C-H functionalization reactions, owing to its ready availability and high reactivity. Although a number of cobalt-catalyzed C(sp(2))-H functionalization reactions have been reported to date, C(sp(3))-H functionalization reactions remain challenging. This Focus Review summarizes recent progress in cobalt-catalyzed C(sp(3))-H functionalization reactions that involve C-H activation to form organometallic intermediates.
  • Narumi Komami, Keitaro Matsuoka, Tatsuhiko Yoshino, Shigeki Matsunaga
    Synthesis (Germany) 50 10 2067 - 2075 2018年05月17日 [査読有り][通常論文]
     
    Palladium-catalyzed germylation of aryl bromides and aryl triflates using commercially available hexamethyldigermane is described. Optimized reaction conditions afforded various functionalized aryltrimethylgermanes, including drug-like molecules, in moderate to good yields, demonstrating the versatility of the presented protocols.
  • Takahiro Tomino, Hirotada Tajiri, Takaaki Tatsuguchi, Takahiro Shirai, Kounosuke Oisaki, Shigeki Matsunaga, Fumiyuki Sanematsu, Daiji Sakata, Tomoharu Yoshizumi, Yoshihiko Maehara, Motomu Kanai, Jean-François Cote, Yoshinori Fukui, Takehito Uruno
    Biochemical and Biophysical Research Communications 497 1 298 - 304 2018年02月 [査読有り][通常論文]
  • Nanami Murakami, Misaki Yoshida, Tatsuhiko Yoshino, Shigeki Matsunaga
    Chemical and Pharmaceutical Bulletin 66 1 51 - 54 2018年01月 [査読有り][通常論文]
     
    Cp∗Co(III)-catalyzed (Cp∗=pentamethylcyclopentadienyl) C-H bond functionalization of 6-arylpurines using gemdifluoroalkenes and allyl fluorides is described. The reaction with gem-difluoroalkenes afforded monofluoroalkenes with high (Z)-selectivity, while the reaction with allyl fluorides led to C-H allylation in moderate (Z)-selectivity. Both reactions proceeded using a user-friendly single-component catalyst [Cp∗Co(CH3CN)3](SbF6)2 in fluorinated alcohol solvents without any additives. Robustness was also demonstrated by a preparative-scale reaction under air.
  • Atsushi Furukawa, Kosuke Kakita, Tomoki Yamada, Mikihiro Ishizuka, Jiro Sakamoto, Nanao Hatori, Naoyoshi Maeda, Fumina Ohsaka, Takashi Saitoh, Takao Nomura, Kimiko Kuroki, Hisanori Nambu, Hisashi Arase, Shigeki Matsunaga, Masahiro Anada, Toyoyuki Ose, Shunichi Hashimoto, Katsumi Maenaka
    JOURNAL OF BIOLOGICAL CHEMISTRY 292 51 21128 - 21136 2017年12月 [査読有り][通常論文]
     
    Before entering host cells, herpes simplex virus-1 uses its envelope glycoprotein B to bind paired immunoglobulin-like type 2 receptor alpha (PILR alpha) on immune cells. PILR alpha belongs to the Siglec (sialic acid (SA)-binding immunoglobulin-like lectin)- like family, members of which bind SA. PILR alpha is the only Siglec member to recognize not only the sialylated O-linked sugar T antigen (sTn) but also its attached peptide region. We previously determined the crystal structure of PILR alpha complexed with the sTn-linked glycopeptide of glycoprotein B, revealing the simultaneous recognition of sTn and peptide by the receptor. However, the contribution of each glycopeptide component to PILR alpha binding was largely unclear. Here, we chemically synthesized glycopeptide derivatives and determined the thermodynamic parameters of their interaction with PILR alpha. We show that glycopeptides with different sugar units linking SA and peptides (i.e. "GlcNAc-type" and "deoxy-GlcNAc-type" glycopeptides) have lower affinity and more enthalpy-driven binding than the wild type (i.e. GalNAc-type glycopeptide). The crystal structures of PILR alpha complexed with these glycopeptides highlighted the importance of stereochemical positioning of the O4 atom of the sugar moiety. These results provide insights both for understanding the unique O-glycosylated peptide recognition by the PILR alpha and for the rational design of herpes simplex virus-1 entry inhibitors.
  • Masahiro Anada, Taiki Hanari, Kosuke Kakita, Yasunobu Kurosaki, Kazuki Katsuse, Yuta Sunadoi, Yu Jinushi, Koji Takeda, Shigeki Matsunaga, Shunichi Hashimoto
    ORGANIC LETTERS 19 20 5581 - 5584 2017年10月 [査読有り][通常論文]
     
    The first total synthesis of brasilicardins A and C, novel diterpenoid saccharide amine acid hybrid metabolites with unique immunosuppressive activity, is described. The key step is a Diels-Alder/reductive angular methylation sequence capitalizing on a trans-fused bicyclic alpha-cyano-alpha,beta-enone as its precursor to construct the 8,10-dimethyltrans/syn/trans,perhydrophenanthierie skeleton. Other notable features include an,anti selective aldol reaction, a stereocontrolled glycosylation of a C2 alcohol, and a one-pot, two-step global deprotection sequence that did not damage these sensitive molecules.
  • Takumi Abe, Takuro Suzuki, Masahiro Anada, Shigeki Matsunaga, Koji Yamada
    ORGANIC LETTERS 19 16 4275 - 4278 2017年08月 [査読有り][通常論文]
     
    A novel indole-2,3-epoxide equivalent, 2-hydroxyindbline-3-triethylammonium bromide, was found, to be a convenient reagent for formal C3-electrophilic reactions of indoles with various nudeophiles. By taking advantage of the nudeophilie character of the oxygen of the 2-hydroxyindo-line the interrupted retro-Claisen interrupted Feist - Benary reactions, with 1,3-dicarbonyl compounds Were efficiently achieved.
  • Ken Sakata, Masami Eda, Yuri Kitaoka, Tatsuhiko Yoshino, Shigeki Matsunaga
    JOURNAL OF ORGANIC CHEMISTRY 82 14 7379 - 7387 2017年07月 [査読有り][通常論文]
     
    The Cp*Co-III-catalyzed C H functionalization reaction of indoles with alkynes was examined using M06-level DFT calculations. The bond in the alkyne was inserted into the C C bond of an intermediate alkenyl Co complex given by the acetate-assisted C H bond activation step. Then the reaction pathway bifurcated into alkenylation and annulation pathways. In the case where AcOH, which was eliminated by ligand exchange for the alkyne, recoordinated to the Co atom, alkenylation proceeded via proton transfer. On the other hand, the annulation pathway to give pyrroloindolone became significant in the case where the ring-closure C C bond formation was followed by the attachment of AcOH. At a high temperature (393 K), the difference in the Gibbs free energy between the transition state for proton transfer in the alkenylation pathway and that for the ring-closure C C bond formation in the annulation pathway was relatively small, so both reactions could proceed. In addition, we also found another pathway to provide the directing-group migration on the way to annulation. This finding well, elucidates the recent experimental report that tetrasubstituted alkenes were obtained as the major product under different conditions.
  • Seiya Fukagawa, Yingjie Xu, Masahiro Anada, Tatsuhiko Yoshino, Shigeki Matsunaga
    HETEROCYCLES 94 7 1337 - 1350 2017年07月 [査読有り][通常論文]
     
    Catalytic enantioselective desymmetrization of meso-aziridines with fluoromalonates is described. Optimization studies revealed that the appropriate combination of Bronsted basic metal and Lewis acidic metal is important for promoting the reaction using fluoromalonates. A heterodinuclear Gd(OiPr)(3)/Y(OTf)(3)/Schiff base = 1:1:1 was the best catalyst, and ring-opening adducts, synthetic precursors for alpha-fluoro-gamma-amino acids, were obtained in 98%similar to 17% yield and >99.5%similar to 99% ee. Transformation of the ring-opening adduct into alpha-fluoro-gamma-lactam was also demonstrated.
  • Ikemoto. H, Tanaka, R, Sakata, K, Kanai, M, Yoshino, T, Matsunaga, S
    Angew. Chem., Int. Ed. 56 25 7156 - 7160 2017年06月 [査読有り][通常論文]
     
    A highly atom economical and stereoselective synthesis of tetrasubstituted alpha,beta-unsaturated amides was achieved by a Cp*Co-III-catalyzed C-H alkenylation/directing group migration sequence. A carbamoyl directing group, which is typically removed after C-H functionalization, worked as an internal acylating agent and migrated onto the alkene moiety of the product. The directing group migration was realized with the Cp*Co-III catalyst, while a related Cp*Rh-III catalyst did not promote the migration process. The product was further converted into two types of tricyclic compounds, one of which had fluorescent properties.
  • Yoshida, M, Kawai, K, Tanaka, R, Yoshino, T, Matsunaga, S
    Chem. Commun. 53 44 5974 - 5977 2017年06月 [査読有り][通常論文]
     
    Cp*Co-III-catalyzed directed C-H trifluoromethylthiolation using N-trifluoromethylthiodibenzenesulfonimide as an electrophilic SCF3 source is described. 6-Arylpurines, an important structural motif in medicinal chemistry, and 2-phenylpyridines selectively afforded mono-trifluoromethylthiolated products in moderate to good yields using an inexpensive first-row transition metal catalyst.
  • Misaki Yoshida, Kentaro Kawai, Ryo Tanaka, Tatsuhiko Yoshino, Shigeki Matsunaga
    CHEMICAL COMMUNICATIONS 53 44 5974 - 5977 2017年06月 [査読有り][通常論文]
     
    Cp*Co-III-catalyzed directed C-H trifluoromethylthiolation using N-trifluoromethylthiodibenzenesulfonimide as an electrophilic SCF3 source is described. 6-Arylpurines, an important structural motif in medicinal chemistry, and 2-phenylpyridines selectively afforded mono-trifluoromethylthiolated products in moderate to good yields using an inexpensive first-row transition metal catalyst.
  • Hirotada Tajiri, Takehito Uruno, Takahiro Shirai, Daisuke Takaya, Shigeki Matsunaga, Daiki Setoyama, Mayuki Watanabe, Mutsuko Kukimoto-Niino, Kounosuke Oisaki, Miho Ushijima, Fumiyuki Sanematsu, Teruki Honma, Takaho Terada, Eiji Oki, Senji Shirasawa, Yoshihiko Maehara, Dongchon Kang, Jean-Francois Cote, Shigeyuki Yokoyama, Motomu Kanai, Yoshinori Fukui
    CELL REPORTS 19 5 969 - 980 2017年05月 [査読有り][通常論文]
     
    Oncogenic Ras plays a key role in cancer initiation but also contributes to malignant phenotypes by stimulating nutrient uptake and promoting invasive migration. Because these latter cellular responses require Rac-mediated remodeling of the actin cytoskeleton, we hypothesized that molecules involved in Rac activation may be valuable targets for cancer therapy. We report that genetic inactivation of the Rac-specific guanine nucleotide exchange factor DOCK1 ablates both macropinocytosis-dependent nutrient uptake and cellular invasion in Ras-transformed cells. By screening chemical libraries, we have identified 1-(2-(3'-(trifluoromethyl)[ 1,1'-biphenyl]-4-yl)-2-oxoethyl)-5-pyrrolidinylsulfonyl-2(1H)-pyridone (TBOPP) as a selective inhibitor of DOCK1. TBOPP dampened DOCK1-mediated invasion, macropinocytosis, and survival under the condition of glutamine deprivation without impairing the biological functions of the closely related DOCK2 and DOCK5 proteins. Furthermore, TBOPP treatment suppressed cancer metastasis and growth in vivo in mice. Our results demonstrate that selective pharmacological inhibition of DOCK1 could be a therapeutic approach to target cancer cell survival and invasion.
  • Atmika Paudel, Hiroshi Hamamoto, Suresh Panthee, Keiichi Kaneko, Shigeki Matsunaga, Motomu Kanai, Yutaka Suzuki, Kazuhisa Sekimizu
    FRONTIERS IN MICROBIOLOGY 8 2017年04月 [査読有り][通常論文]
     
    Synthetic compounds are a vital source of antimicrobial agents. To uncover therapeutically effective antimicrobial agents from a chemical library, we screened over 100,000 synthetic compounds for in vitro antimicrobial activity against methicillin-resistant Staphylococcus aureus and evaluated the in vivo therapeutic effectiveness of the hits in S. aureus-infected silkworms. Three antimicrobial agents exhibited therapeutic effects in the silkworm infection model. One of these, GPI0363, a novel spiro-heterocyclic compound, was bacteriostatic and inhibited RNA synthesis in S. aureus cells. GPI0363-resistant S. aureus strains harbored a point mutation in the gene encoding the primary sigma factor, SigA, of RNA polymerase, and this mutation was responsible for the resistance to GPI0363. We further revealed that GPI0363 could bind to SigA, inhibit promoter-specific transcription in vitro, and prolong the survival of mice infected with methicillin-resistant S. aureus. Thus, GPI0363 is an attractive candidate therapeutic agent against drug-resistant S. aureus infections.
  • Yoshino, T, Matsunaga, S
    Adv. Synth. Catal. 359 8 1245 - 1262 2017年04月 [査読有り][招待有り]
     
    High-valent (pentamethylcyclopentadienyl) cobalt(III) [Cp*Co(III)] catalysts were found as inexpensive alternatives to (pentamethylcyclopentadienyl) rhodium(III) [Cp*Rh(III)] catalysts in the field of C-H bond functionalization, and applied to a variety of transformations. In this review, after the discovery and early examples of Cp*Co(III)-catalyzed C-H bond functionalization are summarized, the unique reactivity and selectivity of Cp*Co(III) and the differences between the cobalt and rhodium catalysis are intensively discussed. Such differences are assumed to be caused by the lower electronegativity, hard nature, and smaller ionic radius of cobalt.
  • Shota Kato, Yutaka Saga, Masahiro Kojima, Hiromu Fuse, Shigeki Matsunaga, Arisa Fukatsu, Mio Kondo, Shigeyuki Masaoka, Motomu Kanai
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 139 6 2204 - 2207 2017年02月 [査読有り][通常論文]
     
    Hybrid catalyst systems to achieve acceptorless dehydrogenation of N-heterocycles and tetrahydronaphthalenes-model substrates for liquid organic hydrogen carriers-were developed. A binary hybrid catalysis comprising an acridinium phototedox catalyst and a Pd metal catalyst was effective for the dehydrogenation of N-heterocycles, whereas a ternary hybrid catalysis comprising an acridinium photoredox catalyst, a Pd metal catalyst, and a thiophosphoric imide organocatalyst achieved dehydrogenation of tetrahydronaphthalenes. These hybrid catalyst systems allowed for 2 molar equiv of H-2 gas release from six-membered N-heterocycles and tetrahydronaphthalenes under mild conditions, i.e., visible light irradiation at rt. The combined use of two or three different catalyst types was essential for the catalytic activity.
  • Shota Kato, Yutaka Saga, Masahiro Kojima, Hiromu Fuse, Shigeki Matsunaga, Arisa Fukatsu, Mio Kondo, Shigeyuki Masaoka, Motomu Kanai
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 139 6 2204 - 2207 2017年02月 [査読有り][通常論文]
     
    Hybrid catalyst systems to achieve acceptorless dehydrogenation of N-heterocycles and tetrahydronaphthalenes-model substrates for liquid organic hydrogen carriers-were developed. A binary hybrid catalysis comprising an acridinium phototedox catalyst and a Pd metal catalyst was effective for the dehydrogenation of N-heterocycles, whereas a ternary hybrid catalysis comprising an acridinium photoredox catalyst, a Pd metal catalyst, and a thiophosphoric imide organocatalyst achieved dehydrogenation of tetrahydronaphthalenes. These hybrid catalyst systems allowed for 2 molar equiv of H-2 gas release from six-membered N-heterocycles and tetrahydronaphthalenes under mild conditions, i.e., visible light irradiation at rt. The combined use of two or three different catalyst types was essential for the catalytic activity.
  • Taku Miyazawa, Kozue Imai, Motoki Ito, Koji Takeda, Masahiro Anada, Shigeki Matsunaga, Shunichi Hashimoto
    HETEROCYCLES 95 2 1211 - 1229 2017年01月 [査読有り][招待有り]
     
    The first diastereo- and enantioselective construction of bridged bicyclic ring systems by an intramolecular C-H insertion reaction is described. With dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate], Rh2(S-PTTL)4, the C-H insertion of alpha-alkyl-alpha-diazoesters containing an ethylene ketal moiety at the gamma-position provided methyl 6,7-dioxabicyclo[2.2.1]heptane-3-carboxylate derivatives with up to 95% ee and perfect diastereoselectivity.
  • Taku Miyazawa, Kozue Imai, Motoki Ito, Koji Takeda, Masahiro Anada, Shigeki Matsunaga, Shunichi Hashimoto
    HETEROCYCLES 95 2 1211 - 1229 2017年01月 [査読有り][通常論文]
     
    The first diastereo- and enantioselective construction of bridged bicyclic ring systems by an intramolecular C-H insertion reaction is described. With dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate], Rh2(S-PTTL)4, the C-H insertion of alpha-alkyl-alpha-diazoesters containing an ethylene ketal moiety at the gamma-position provided methyl 6,7-dioxabicyclo[2.2.1]heptane-3-carboxylate derivatives with up to 95% ee and perfect diastereoselectivity.
  • Tatsuhiko Yoshino, Shigeki Matsunaga
    ADVANCES IN ORGANOMETALLIC CHEMISTRY, VOL 68 68 197 - 247 2017年 [査読有り][通常論文]
  • Naoyoshi Maeda, Atsushi Furukawa, Kosuke Kakita, Masahiro Anada, Shunichi Hashimoto, Shigeki Matsunaga, Kimiko Kuroki, Toyoyuki Ose, Akihisa Kato, Jun Arii, Yasushi Kawaguchi, Hisashi Arase, Katsumi Maenaka
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 39 11 1897 - 1902 2016年11月 [査読有り][通常論文]
     
    Herpes simplex virus type 1 (HSV-1) is a causative agent for a variety of diseases. Although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with DNA kinases, their continuous administration leads to an increase in the frequency of drug-resistant HSV-1, which is an important clinical issue that requires urgent solution. Recently, we reported that the sialylated O-linked sugar T antigen (sTn) and its attached peptide region (O-glycosylated sTn peptide) derived from the HSV-1 glycoprotein B (gB) protein inhibited HSV-1 infection by specifically targeting paired immunoglobulin-like type 2 receptor alpha (PILR alpha) in vitro. In this study, to further identify novel inhibitors of gB-mediated HSV-1 infection in vitro, we established a cell-based fusion assay for rapid drug screening. Chinese hamster ovary (CHO) cells were transfected with expression plasmids for HSV-1 gB, gD, gH, and gL, and T7 RNA polymerase, and were designated as the effector cells. The CHO-K1 cells stably expressing PILRa were transfected with the expression plasmid for firefly luciferase under the T7 promoter, and were designated as the target cells. The effector and target cells were co-cultured, and luminescence was measured when both cells were successfully fused. Importantly, we found that cell-to-cell fusion was specifically inhibited by O-glycosylated sTn peptide in a dose dependent manner. Our results suggested that this virus-free cell-based fusion assay system could be a useful and promising approach to identify novel inhibitors of gB-mediated HSV-1 infection, and will aid in the development of antiviral therapeutic strategies for HSV-1-associated diseases.
  • Ryo Tanaka, Hideya Ikemoto, Motomu Kanai, Tatsuhiko Yoshino, Shigeki Matsunaga
    ORGANIC LETTERS 18 21 5732 - 5735 2016年11月 [査読有り][通常論文]
     
    A site-, regio-, syn-, and monoselective alkenylation of dimethylcarbamoyl-protected pyrroles proceeded using a catalytic amount of [Cp*Co(CH3CN)(3)](SbF6)(2) and KOAc. A variety of internal alkynes with several functional groups and a terminal alkyne afforded hydropyrrolation products in a selective manner in good to excellent yield. The site-selectivity (C2/C5 selectivity) observed for C3-substituted pyrroles is noteworthy because Cp*R-III-catalyzed conditions afforded only a moderate yield and low selectivity. The conditions described here provide general and straightforward access to unsymmetrically mono- and disubstituted pyrrole derivatives.
  • Miyazawa, T, Minami, K, Ito, M, Anada, M, Matsunaga, S, Hashimoto, S
    Tetrahedron 72 27-28 3939 - 3947 2016年07月 [査読有り][通常論文]
     
    The first enantio-and diastereoselective construction of fused bicyclic ring systems via intramolecular C-H insertion reaction of sigma-symmetric alpha-alkyl-alpha-diazoesters is described. With dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate], Rh-2(S-PITL)(4), the C-H insertion proceeded in a chemoselective manner to give methyl bicyclo[3.3.0]oct-7-ene-2-carboxylate and methyl bicyclo[4.3.01nonane-7-carboxylate derivatives with up to 99% ee and perfect cis diastereoselectivity. The utility of this protocol was demonstrated by the catalytic asymmetric synthesis of a key intermediate in Whitesell's synthesis of udoteatrial hydrate. (C) 2016 Elsevier Ltd. All rights reserved.
  • Bunno, Y, Murakami, N, Suzuki, Y, Kanai, M, Yoshino, T, Matsunaga, S
    Org. Lett. 18 9 2216 - 2219 2016年 [査読有り][通常論文]
     
    Cp*Co-III-catalyzed C-H allylation of various aromatic C-H bonds using allyl alcohols as allylating reagents is described. Improved reaction conditions using fluorinated alcohol solvents afforded efficient directed C-H allylation of 6-arylpurines, benzamides, and a synthetically useful Weinreb amide with good functional group compatibility.
  • Lin, L. Q., Yamamoto, K., Mitsunuma, H., Kanzaki, Y., Matsunaga, S., Kanai, M.
    Journal of the American Chemical Society 137 49 15418 - 15421 2015年 [査読有り][通常論文]
     
    We report here catalytic asymmetric iterative and domino cross-aldol reactions between aldehydes, endowed with a high level of robustness, flexibility, and generality. A Cu(I)-DTBM-SEGPHOS complex catalyzes an asymmetric cross-aldol reaction between acceptor aldehydes and boron enolates derived from donor aldehydes, which are generated through Ir-catalyzed isomerization of allyloxyboronates. The unit process can be repeated using the aldol products in turn as acceptor substrates for the subsequent asymmetric aldol reaction. The donor aldehydes and stereoselectivity can be flexibly switched in a stepwise manner for the double-aldol reaction. Furthermore, asymmetric triple- and quadruple-aldol reactions are possible in one-pot using the appropriate amounts of donors and amine additives, rapidly elongating the carbon skeleton with controlling up to eight stereocenters. The method should be useful for straightforward synthesis of enantiomerically and diaster-eomerically enriched 1,3-polyols.
  • Sun, B., Yoshino, T., Kanai, M., Matsunaga, S.
    Angewandte Chemie-International Edition 54 44 12968 - 12972 2015年 [査読有り][通常論文]
     
    The synthesis of isoquinolines by site-selective CH activation of O-acyl oximes with a Cp*Co-III catalyst is described. In the presence of this catalyst, the CH activation of various unsymmetrically substituted O-acyl oximes selectively occurred at the sterically less hindered site, and reactions with terminal as well as internal alkynes afforded the corresponding products in up to 98% yield. Whereas the reactions catalyzed by the Cp*Co-III system proceeded with high site selectivity (15:1 to 20:1), use of the corresponding Cp*Rh-III catalysts led to low selectivities and/or yields when unsymmetrical O-acyl oximes and terminal alkynes were used. Deuterium labeling studies indicate a clear difference in the site selectivity of the CH activation step under Cp*Co-III and Cp*Rh-III catalysis.
  • Suzuki, Y., Sun, B., Sakata, K., Yoshino, T., Matsunaga, S., Kanai, M.
    Angewandte Chemie-International Edition 54 34 9944 - 9947 2015年 [査読有り][通常論文]
     
    The unique reactivity of [Cp*Co-III] over [Cp*Rh-III] was demonstrated. A cationic [Cp*Co-III] catalyst promoted direct dehydrative C-H allylation with non-activated allyl alcohols, thus giving C2-allylated indoles, pyrrole, and phenylpyrazole in good yields, while analogous [Cp*Rh-III] catalysts were not effective. The high g-selectivity and C2-selectivity indicated that the reaction proceeded by directing-group-assisted C-H metalation. DFT calculations suggested that the gamma-selective substitution reaction proceeded by C-H metalation and insertion of a C-C double bond, with subsequent beta-hydroxide elimination. The [Cp*Co-III] catalyst favored beta-hydroxide elimination over beta-hydride elimination.
  • Suzuki, Y., Sun, B., Yoshino, T., Kanai, M., Matsunaga, S.
    Tetrahedron 71 26-27 4552 - 4556 2015年 [査読有り][招待有り]
     
    The utility of Cp-Co(III)-catalysts was expanded to oxidative C-C bond-forming reaction. In situ-generated Cp*Co(III)-catalyst, rather than a preformed cationic Cp*Co(III)-complex, was effective. Oxidative alkenylation of benzamides and acetanilide with ethyl acrylate proceeded with silver acetate as a stoichiometric oxidant, giving products in up to 93% yield. (C) 2015 Elsevier Ltd. All rights reserved.
  • Yamamoto, S., Matsunaga, S., Kanai, M.
    Heterocycles 90 1 89 - 96 2015年 [査読有り][通常論文]
     
    Cobalt-catalyzed C5-selective C-H functionalization of 4-Me-quinolines is described. A postulated cobalt-hydride catalyst, generated from 2 mol % of CoI2, promoted the reaction of 4-Me-quinolines with styrenes, giving 5,6-dihydro-4H-benzo[de]quinolines (34-55% yield) in one-pot. A plausible reaction mechanism is also described.
  • Sun, B., Yoshino, T., Matsunaga, S., Kanai, M.
    Chemical Communications 51 22 4659 - 4661 2015年 [査読有り][通常論文]
     
    C2-selective indole C-H phosphoramidation was achieved through improved Cp*Co(III) catalysis. A cationic Co(III) species generated in situ from a Cp*CoI2-dimer showed the best catalytic activity, giving phosphoramidated indoles in 60-86% yield.
  • Shohei Yamamoto, Shigeki Matsunaga, Motomu Kanai
    HETEROCYCLES 90 1 89 - 96 2015年01月 [査読有り][通常論文]
     
    Cobalt-catalyzed C5-selective C-H functionalization of 4-Me-quinolines is described. A postulated cobalt-hydride catalyst, generated from 2 mol % of CoI2, promoted the reaction of 4-Me-quinolines with styrenes, giving 5,6-dihydro-4H-benzo[de]quinolines (34-55% yield) in one-pot. A plausible reaction mechanism is also described.
  • Bo Sun, Tatsuhiko Yoshino, Shigeki Matsunaga, Motomu Kanai
    CHEMICAL COMMUNICATIONS 51 22 4659 - 4661 2015年 [査読有り][通常論文]
     
    C2-selective indole C-H phosphoramidation was achieved through improved Cp*Co(III) catalysis. A cationic Co(III) species generated in situ from a Cp*CoI2-dimer showed the best catalytic activity, giving phosphoramidated indoles in 60-86% yield.
  • Paudel, A., Kaneko, K., Watanabe, A., Matsunaga, S., Kanai, M., Hamamoto, H., Sekimizu, K.
    Journal of Antibiotics 67 2 203 - 203 2014年 [査読有り][通常論文]
  • Kato, S., Kanai, M., Matsunaga, S.
    Heterocycles 88 1 475 - 491 2014年 [査読有り][通常論文]
     
    Direct catalytic asymmetric aldol-type reaction of aldehydes with isothiocyanato oxindoles is described. A dinuclear (S)-Ni-2-Schiff base complex (0.1-10 mol %) efficiently catalyzed the addition of isothiocyanato oxindoles to aliphatic aldehydes, giving spirooxindole products in 80-99% ee and 81:19-91:9 dr. A Sr(O-iPr)(2)/Schiff base complex (10 mol %) was utilized for aryl aldehydes and spirooxindole products were obtained in 33-78% ee and 96:4-98:2 dr.
  • Shota Kato, Motomu Kanai, Shigeki Matsunaga
    HETEROCYCLES 88 1 475 - 491 2014年01月 [査読有り][通常論文]
     
    Direct catalytic asymmetric aldol-type reaction of aldehydes with isothiocyanato oxindoles is described. A dinuclear (S)-Ni-2-Schiff base complex (0.1-10 mol %) efficiently catalyzed the addition of isothiocyanato oxindoles to aliphatic aldehydes, giving spirooxindole products in 80-99% ee and 81:19-91:9 dr. A Sr(O-iPr)(2)/Schiff base complex (10 mol %) was utilized for aryl aldehydes and spirooxindole products were obtained in 33-78% ee and 96:4-98:2 dr.
  • Yamamoto, S., Saga, Y., Andou, T., Matsunaga, S., Kanai, M.
    Advanced Synthesis & Catalysis 356 2-3 401 - 405 2014年 [査読有り][通常論文]
     
    The cobalt-catalyzed direct C-4 selective alkylation of quinolines is described. The reaction conditions used previously for pyridines were fully modified to achieve C-4 selectivity in quinoline alkylation. Cobalt(II) acetate [Co(OAc)(2)] (2-4mol%) in combination with butyllithium (BuLi) and pyridine was best, and C-4 alkylation proceeded in 54-95% yield with C-4/C-2=>20:1-2.5:1 and branched/linear=>20:1 selectivity.
  • Sun, B., Yoshino, T., Matsunaga, S., Kanai, M.
    Advanced Synthesis & Catalysis 356 7 1491 - 1495 2014年 [査読有り][通常論文]
     
    The readily available carbonyl(pentamethylcyclopentadienyl)cobalt diiodide complex [Cp*Co(CO)I-2] was successfully utilized as the precursor of a cationic cobalt(III) active catalyst for directed CH bond functionalization. The complex Cp*Co(CO)I-2 (2.5-1.25mol%), in combination with silver hexafluoroantimonate (AgSbF6) and potassium acetate (KOAc), efficiently catalyzed the directed C-2 selective amidation of indoles with sulfonyl azides, and the corresponding products were obtained in 85-98% yield.
  • Matsunaga, S., Shibasaki, M.
    Chemical Communications 50 9 1044 - 1057 2014年 [査読有り][通常論文]
     
    Cooperative catalysis has proven to be a powerful strategy for realizing high reactivity and selectivity in asymmetric transformations. A variety of cooperative asymmetric catalysts have been developed over the last two decades. In this feature article, recent advances from our research on cooperative asymmetric catalysis, focusing on dinuclear Schiff base catalysis, are described. Design of dinuclear Schiff base catalysts and their applications in several asymmetric C-C and C-N bond-forming reactions under simple proton transfer conditions with perfect atom-economy are discussed in detail.
  • Ikemoto, H., Yoshino, T., Sakata, K., Matsunaga, S., Kanai, M.
    Journal of the American Chemical Society 136 14 5424 - 5431 2014年 [査読有り][通常論文]
     
    A unique synthetic utility of a Cp*Co-III catalyst in comparison with related Cp*Rh-III catalysts is described. A C2-selective indole alkenylation/annulation sequence proceeded smoothly with catalytic amount of a [Cp*Co-III(C6H6)](PF6)(2) complex and KOAc. Intramolecular addition of an alkenyl-Cp*Co species to a carbamoyl moiety gave pyrroloindolones in 58-89% yield in one pot. Clear difference was observed between the catalytic activity of the Cp*Co-III complex and those of Cp*Rh-III complexes, highlighting the unique nucleophilic activity of the organocobalt species. The Cp*Co-III catalysis was also suitable for simple alkenylation process of N-carbamoyl indoles, and broad range of alkynes, including terminal alkynes, were applicable to give C2-alkenylated indoles in 50-99% yield. Mechanistic studies on C-H activation step under Cp*Co-III catalysis with the aid of an acetate unit as well as evaluation of the difference between organo-Co-III species and organo-Rh-III species are also described.
  • Xu, Y. J., Kaneko, K., Kanai, M., Shibasaki, M., Matsunaga, S.
    Journal of the American Chemical Society 136 25 9190 - 9194 2014年 [査読有り][通常論文]
     
    Regiodivergent parallel kinetic resolution of aziridines with malonates was achieved under dinuclear Schiff base catalysis. The regiodivergent reaction proceeded under catalyst-control irrespective of the substituents on the aziridines, and 2.5-10 mol % of a Y(OTf)(3)/La(OiPr)(3)/a dinucleating Schiff base = 1:1:1 mixture gave versatile gamma-amino acid derivatives in 96 -> 99.5% ee. Not only terminal but also internal racemic aziridines reacted smoothly under suitably combined Lewis acid/Bronsted base catalysis.
  • Luqing Lin, Kumiko Yamamoto, Shigeki Matsunaga, Motomu Kanai
    Chemistry - An Asian Journal 8 12 2974 - 2983 2013年12月 [査読有り][通常論文]
     
    The chemoselective generation of aldehyde-derived enolates to realize an aldehyde - aldehyde cross-aldol reaction is described. A combined Rh/dippf system efficiently promoted the isomerization/aldol sequence by using primary allylic, homoallylic, and bishomoallylic alcohols secondary allylic and homoallylic alcohols and trialkoxyboranes that were derived from primary allylic and homoallylic alcohols. The reaction proceeded at ambient temperature under base-free conditions, thus giving cross-aldol products with high chemoselectivity. Mechanistic studies, as well as its application to double-aldol processes under protecting-group-free conditions, are also described. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
  • Paudel A, Kaneko K, Watanabe A, Matsunaga S, Kanai M, Hamamoto H, Sekimizu K
    The Journal of antibiotics 66 11 663 - 667 2013年11月 [査読有り][通常論文]
     
    An iminothiadiazolo-pyrimidinone derivative, 0002-04-KK, harboring a furan moiety, acts as an antimicrobial agent with a minimum inhibitory concentration (MIC) against Staphylococcus aureus of 25 μg ml -1. Several derivatives of 0002-04-KK were synthesized and among them 0026-59-KK, harboring a nitrofuran moiety, had the most potent antimicrobial activity with an MIC of 6 μg ml -1. Both 0002-04-KK and 0026-59-KK inhibited the biosynthesis of DNA, RNA and proteins. Peptidoglycan biosynthesis was inhibited by 0026-59-KK, and slightly inhibited by 0002-04-KK. Derivative 0002-04-KK showed bactericidal activity in contrast to the bacteriostatic activity of 0002-04-KK. Derivative 0002-04-KK had less toxicity in silkworms (lethal dose fifty (LD 50): > 230 μg g -1) than 0002-04-KK (LD 50: 100 μg g -1). The bactericidal activity against S. aureus was because of the nitrofuran moiety. These findings suggest that iminothiadiazolo-pyrimidinone compounds could be used as lead molecules to develop antimicrobial agents. © 2013 Japan Antibiotics Research Association.
  • Shota Kato, Motomu Kanai, Shigeki Matsunaga
    Chemistry - An Asian Journal 8 8 1768 - 1771 2013年08月 [査読有り][通常論文]
     
    One-step approach: A homodinuclear nickel Schiff base catalyst was utilized for the title reaction, thus providing easy access to spirocyclic oxindole compounds in one step. High enantioselectivity as well as high catalyst turnover number (TON, up to 850) were achieved at ambient temperature. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
  • Tatsuhiko Yoshino, Hideya Ikemoto, Shigeki Matsunaga, Motomu Kanai
    CHEMISTRY-A EUROPEAN JOURNAL 19 28 9142 - 9146 2013年07月 [査読有り][通常論文]
  • Kanai Motomu, Matsunaga Shigeki
    SYNTHESIS-STUTTGART 45 11 A68 - A70 2013年06月 [査読有り][通常論文]
  • Keiichi Kaneko, Tatsuhiko Yoshino, Shigeki Matsunaga, Motomu Kanai
    ORGANIC LETTERS 15 10 2502 - 2505 2013年05月 [査読有り][通常論文]
     
    Cu-catalyzed intermolecular carboamination of alkenes is described. The reaction of terminal alkenes and an internal alkene with N-fluorobenzenesulfonimide was promoted by 2.5 mol % of a Cu(I)-salt at 60 degrees C, and six-membered ring sultams were obtained in 91-44% yields.
  • Shigeki Matsunaga, Masakatsu Shibasaki
    SYNTHESIS-STUTTGART 45 4 421 - 437 2013年02月 [査読有り][通常論文]
     
    Multimetallic salen and related Schiff base complexes designed for cooperative asymmetric catalysis are introduced. First, studies to enhance the cooperative function of two distinct metal-salen units using covalently linked metal-salen complexes, supramolecular bimetallic salens as well as mu-oxo-bridged metal salens are described. Then, studies to design dinuclear Schiff base catalysts that exhibit unique intramolecular cooperative functions of two distinct metals are discussed in detail.
  • Yoshino, T., Ikemoto, H., Matsunaga, S., Kanai, M.
    Angewandte Chemie-International Edition 52 8 2207 - 2211 2013年 [査読有り][通常論文]
  • Takashi Andou, Yutaka Saga, Hirotomo Komai, Shigeki Matsunaga, Motomu Kanai
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 52 11 3213 - 3216 2013年 [査読有り][通常論文]
     
    How pyridine got its tail: A new catalyst for the atom-economical C4-selective direct alkylation of pyridines is described. A combination of CoBr2 and LiBEt3H catalyzes the reaction of pyridines with 1-alkenes at 70 °C to give alkylation products with C4/C2 ratios of > 20:1. Substrate/catalyst ratios of up to 4000, and a turnover number of 3440 were achieved. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
  • Hirooki Tanabe, Yingjie Xu, Bo Sun, Shigeki Matsunaga, Masakatsu Shibasaki
    HETEROCYCLES 86 1 611 - 622 2012年12月 [査読有り][通常論文]
     
    Direct catalytic asymmetric vinylogous Michael reaction is described. 2.5 mol % of homobimetallic (S)-Ni-2-Schiff base complex efficiently catalyzed the addition of alpha,beta-unsaturated gamma-butyrolactam to nitroalkenes under simple proton transfer conditions, giving vinylogous Michael products in 83-99% yield, 16:1-> 30:1 dr, and 96-99% ee.
  • Hirotomo Komai, Tatsuhiko Yoshino, Shigeki Matsunaga, Motomu Kanai
    SYNTHESIS-STUTTGART 44 14 2185 - 2194 2012年07月 [査読有り][通常論文]
     
    Lewis acid catalyzed benzylic C-H bond functionalization of alkyl-substituted azaarenes is described. The addition to N-tosyl imines proceeded under solvent-free conditions using various Lewis acids. Cu(OTf)(2) was the best Lewis acid, and 1,2-addition proceeded at 60-120 degrees C, giving products in 23-92% yield. On the other hand, strongly Lewis acidic rare-earth metal triflates, Sc(OTf)(3) and Y(OTf)(3), were essential to promote the 1,4-addition of alkyl-substituted azaarenes to enones, and products were obtained in 60-96% yield.
  • Yudai Suzuki, Motomu Kanai, Shigeki Matsunaga
    CHEMISTRY-A EUROPEAN JOURNAL 18 25 7654 - 7657 2012年06月 [査読有り][通常論文]
  • Shigeki Matsunaga
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 70 3 278 - 284 2012年03月 [査読有り][通常論文]
  • Toshihiko Sone, Akitake Yamaguchi, Shigeki Matsunaga, Masakatsu Shibasaki
    MOLECULES 17 2 1617 - 1634 2012年02月 [査読有り][通常論文]
     
    Catalytic asymmetric Corey-Chaykovsky epoxidation of various ketones with dimethyloxosulfonium methylide using a heterobimetallic La-Li-3-BINOL complex (LLB) is described. The reaction proceeded smoothly at room temperature in the presence of achiral phosphine oxide additives, and 2,2-disubstituted terminal epoxides were obtained in high enantioselectivity (97%-91% ee) and yield (>99%-88%) from a broad range of methyl ketones with 1-5 mol% catalyst loading. Enantioselectivity was strongly dependent on the steric hindrance, and other ketones, such as ethyl ketones and propyl ketones resulted in slightly lower enantioselectivity (88%-67% ee).
  • Shinsuke Mouri, Zhihua Chen, Shigeki Matsunaga, Masakatsu Shibasaki
    HETEROCYCLES 84 2 879 - 892 2012年01月 [査読有り][通常論文]
     
    Catalytic asymmetric synthesis of 3-aminooxindoles with a tetrasubstituted carbon stereocenter is described. 1 mol% of homobimetallic (R)-Ni-2-Schiff base complex 1 catalyzed asymmetric amination of 3-alkyl-substituted oxindoles with azodicarboxylates to give products in 89-99% yield and 87-99% ee. For 3-aryl-substituted oxindoles, 10 mol% of (R)-Ni-2-Schiff base complex was required to obtain products in 66-98% ee. Postulated catalytic cycle as well as transformation of the products are also described.
  • Shigeki Matsunaga, Masakatsu Shibasaki
    BISMUTH-MEDIATED ORGANIC REACTIONS 311 179 - 197 2012年 [査読有り][通常論文]
     
    Bismuth-catalyzed hydroamination and direct substitution of the hydroxy group in alcohols are described in this chapter. Intermolecular 1: 1 hydroamination of 1,3-dienes with carbamates, sulfonamides, and carboxamides was promoted by a combination of Bi(OTf)(3) and Cu(CH3CN)(4)PF6. The mechanistic studies suggested that a cationic bismuth species would be an active species, which selectively promotes 1: 1 hydroamination to give allylic amides in up to 96% yield. The cationic bismuth species was also applicable for hydroamination of vinyl arenes. The combination of Bi(OTf)(3) and KPF6 was an excellent catalyst for direct substitution of the hydroxy group in allylic, propargylic, and benzylic alcohols with carbamates, sulfonamides, and carboxamides, giving allylic, propargylic, and benzylic amides, respectively, in up to 99% yield in one step.
  • Harunobu Mitsunuma, Masakatsu Shibasaki, Motomu Kanai, Shigeki Matsunaga
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 51 21 5217 - 5221 2012年 [査読有り][通常論文]
  • Shota Kato, Tatsuhiko Yoshino, Masakatsu Shibasaki, Motomu Kanai, Shigeki Matsunaga
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 51 28 7007 - 7010 2012年 [査読有り][通常論文]
  • Luqing Lin, Kumiko Yamamoto, Shigeki Matsunaga, Motomu Kanai
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 51 41 10275 - 10279 2012年 [査読有り][通常論文]
  • Shigeki Matsunaga, Tatsuhiko Yoshino
    CHEMICAL RECORD 11 5 260 - 268 2011年09月 [査読有り][通常論文]
     
    Catalytic asymmetric synthesis of unnatural amino acids with vicinal tetrasubstituted chiral carbon stereocenters is described. In the first part, direct catalytic asymmetric aldol reaction of simple non-activated ketone electrophiles with a-substituted a-isothiocyanato ester donors was realized. A Mg/Schiff base catalyst promoted the aldol reaction, and alpha-amino-beta-hydroxy esters were obtained in up to 98% ee and 98:2 d.r. In the second part, the Mg/Schiff base catalyst and a Sr/Schiff base catalyst were utilized for stereodivergent direct asymmetric Mannich-type reaction of ketimines. The Mg/Schiff base catalyst gave syn-alpha,beta-diamino esters, while the Sr/Schiff base catalyst produced anti-a, b-diamino esters in good to high enantioselectivity, up to 97% ee. DOI 10.1002/tcr.201100020
  • Masakatsu Shibasaki, Shigeki Matsunaga
    Privileged Chiral Ligands and Catalysts 295 - 332 2011年04月07日 [査読有り][通常論文]
  • Hirotomo Komai, Tatsuhiko Yoshino, Shigeki Matsunaga, Motomu Kanai
    ORGANIC LETTERS 13 7 1706 - 1709 2011年04月 [査読有り][通常論文]
     
    A Lewis acid catalyzed benzylic C-H bond functionalization of alkyl-substituted azaarenes is described. Sc(OTf)(3) and Y(OTf)(3) promoted the direct addition of alkyl-substituted azaarenes and benzoxazole to enones and an alpha,beta-unsaturated N-acylpyrrole. Products were obtained in 60-96% yield.
  • Yingjie Xu, Luqing Lin, Motomu Kanai, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 133 15 5791 - 5793 2011年04月 [査読有り][通常論文]
     
    Catalytic asymmetric ring-opening of meso-aziridines with malonates is described. The combined use of two rare earth metal sources with different properties promoted the desired ring-opening reaction. A 1:1:1 mixture of a heterobimetallic La(O-iPr)(3)/Yb(OTf)(3)/Schiff base la (0.25-10 mol %) efficiently promoted the reaction of five-, six-, and seven-membered ring cyclic meso-aziridines as well as acyclic meso-aziridines with dimethyl, diethyl, and dibenzyl malonates, giving chiral cyclic and acyclic gamma-amino esters in 99-63% yield and > 99.5-97% ee.
  • Masakatsu Shibasaki, Motomu Kanai, Shigeki Matsunaga, Naoya Kumagai
    BIFUNCTIONAL MOLECULAR CATALYSIS 37 1 - 30 2011年 [査読有り][通常論文]
     
    The utility of several types of multimetallic asymmetric catalysts is reviewed. The appropriate design of multidentate chiral ligands provides homobimetallic, heterobimetallic, and polymetallic catalysts upon complexation with metal cations. Cooperative work of multiple catalytically active sites in the asymmetric multimetallic catalysts allows for enhanced catalytic activity and stereoselectivity over monometallic catalysts. Facile systematic tuning of the asymmetric multimetallic catalysts by manipulation of multidentate ligand structure and combination of metal cations enables the generation of diverse set of catalysts having distinct three-dimensional and catalytic properties, boosting the optimization process to identify the best catalyst for a specific reaction of interest.
  • Mitsunuma H, Matsunaga S
    Chemical communications (Cambridge, England) 47 1 469 - 471 2011年 [査読有り][通常論文]
     
    A homodinuclear Ni-2-Schiff base 1 complex (1-10 mol%) promoted the catalytic asymmetric 1,4-addition reactions of beta-keto esters and an N-Boc oxindole to nitroethylene, giving products in 98-75% ee.
  • Lu G, Yoshino T, Morimoto H, Matsunaga S, Shibasaki M
    Angewandte Chemie (International ed. in English) 50 19 4382 - 4385 2011年 [査読有り][通常論文]
  • Masakatsu Shibasaki, Shigeki Matsunaga
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 68 11 1142 - 1149 2010年11月 [査読有り][通常論文]
     
    In this account, work in our group on the development and applications of a new family of bimetallic, bifunctional asymmetric catalysts based on dinucleating Schiff bases is described. Suitable design of the dinucleating Schiff bases led to the successful development of heterobimetallic transition metal/rare earth metal catalysts as well as homobimetallic transition metal/transition metal catalysts. The concepts involved in catalyst design, applications to asymmetric reactions, mechanistic insights into bimetallic catalysis as well as the catalytic asymmetric synthesis of biologically active compounds are introduced.
  • Takafumi Yukawa, Bianca Seelig, Yingjie Xu, Hiroyuki Morimoto, Shigeki Matsunaga, Albrecht Berkessel, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 132 34 11988 - 11992 2010年09月 [査読有り][通常論文]
     
    The catalytic asymmetric aza-Morita-Baylis-Hillman reaction using unactivated methyl acrylate is described. A simple Lewis acidic metal catalyst, such as La(OTf)(3), was not suitable for the reaction, but rare earth metal alkoxide/linked-BINOL complexes possessing bifunctional Lewis acid and Bronsted base properties efficiently promoted the reaction in combination with an achiral nucleophilic organocatalyst. The combined use of a La(O-iPr)(3)/(S,S)-TMS-linked-BINOL complex with a catalytic amount of DABCO promoted the aza-Morita-Baylis-Hillman reaction of a broad range of N-diphenylphosphinoyl imines. Products from aryl, heteroaryl, and alkenyl imines were obtained in 67-99% yield and 81-95% ee. It is noteworthy that isomerizable alkyl imines could be employed as well, giving products in 78-89% yield and 94-98% ee. Initial rate kinetic studies as well as kinetic isotope effect experiments using alpha-deuterio-methyl acrylate support the importance of both the nucleophilicity of La-enolate and the Bronsted basicity of a La-catalyst for promoting the reaction.
  • Yingjie Xu, Shigeki Matsunaga, Masakatsu Shibasaki
    ORGANIC LETTERS 12 14 3246 - 3249 2010年07月 [査読有り][通常論文]
     
    A syn-selective catalytic asymmetric 1,4-addition of alpha-ketoanilides to nitroalkenes is described. The homodinuclear Ni-2-Schiff base 1b complex was suitable for the reaction, and products were obtained in 61-92% yield, 8.3:1 -> 20:1 syn-selectivity, and 72-98% ee. Stereoselective transformation of the 1,4-adduct to a trisubstituted pyrrolidine was also performed.
  • Shinya Handa, Vijay Gnanadesikan, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 132 13 4925 - 4934 2010年04月 [査読有り][通常論文]
     
    The full details of a catalytic asymmetric syn-selective nitro-Mannich reaction promoted by heterobimetallic Cu/Sm/dinucleating Schiff base complexes are described, demonstrating the effectiveness of the heterobimetallic transition metal/rare earth metal bifunctional catalysis. The first-generation system prepared from Cu(OAc)(2)/Sm(O-iPr)(3)/Schiff base 1a = 1:1:1 with an achiral phenol additive was partially successful for achieving the syn-selective catalytic asymmetric nitro-Mannich reaction. The substrate scope and limitations of the first-generation system remained problematic. After mechanistic studies on the catalyst prepared from Sm(O-iPr)(3), we reoptimized the catalyst preparation method, and a catalyst derived from Sm5O(O-iPr)(13) showed broader substrate generality as well as higher reactivity and stereoselectivity compared to Sm(O-iPr)(3). The optimal system with Sm5O(O-iPr)(13) was applicable to various aromatic, heteroaromatic, and isomerizable aliphatic N-Boc imines, giving products in 66-99% ee and syn/anti = >20:1-13:1. Catalytic asymmetric synthesis of nemonapride is also demonstrated using the catalyst derived from Sm5O(O-iPr)(13).
  • Nicholas E. Shepherd, Hirooki Tanabe, Yingjie Xu, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 132 11 3666 - + 2010年03月 [査読有り][通常論文]
     
    Direct catalytic asymmetric vinylogous reactions of an alpha,beta-unsaturated gamma-butyrolactam as a donor are described. A homodinuclear Ni-2-Schiff base complex promoted a vinylogous Mannich-type reaction of N-Boc imines as well as a vinylogous Michael reaction to nitroalkenes selectively at the gamma-position under simple proton-transfer conditions. Vinylogous Mannich adducts were obtained in 5:1 -> 30:1 dr and 99% ee, and vinylogous Michael adducts were obtained in 16:1 -> 30:1 dr and 93-99% ee.
  • Shinsuke Mouri, Zhihua Chen, Harunobu Mitsunuma, Makoto Furutachi, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 132 4 1255 - + 2010年02月 [査読有り][通常論文]
     
    A highly enantioselective catalytic asymmetric access to 3-aminooxindoles with a tetrasubstituted carbon stereocenter is described. 1-2 mol % of homobimetallic (R)-Ni(2)-Schiff base 1 catalyzed the asymmetric amination of 3-substituted oxindoles with azodicarboxylates to give (R)-products in 99-89% yield and 99-87% ee. Reversal of enantiofacial selectivity was observed between bimetallic and monometallic Schiff base complexes, and monometallic (R)-Ni-Schiff base 2c gave (S)-products in 98-80% ee. Transformation of the products into an optically active oxindole with a spiro-beta-lactam unit and a known key intermediate for AG-041R synthesis is also described.
  • Makoto Furutachi, Zhihua Chen, Shigeki Matsunaga, Masakatsu Shibasaki
    MOLECULES 15 1 532 - 544 2010年01月 [査読有り][通常論文]
     
    Catalytic asymmetric 1,4-addition of beta-keto esters to nitroalkenes is described. 2.5 mol % of a homobimetallic Lewis acid/Bronsted base bifunctional Co-2-Schiff base complex smoothly promoted the reaction in excellent yield (up to 99%), diastereoselectivity, and enantioselectivity (up to >30:1 dr and 98% ee). Catalyst loading was successfully reduced to 0.1 mol %. Mechanistic studies suggested that intramolecular cooperative functions of the two Co-metal centers are important for high catalytic activity and stereoselectivity.
  • Makoto Furutachi, Shinsuke Mouri, Shigeki Matsunaga, Masakatsu Shibasaki
    CHEMISTRY-AN ASIAN JOURNAL 5 11 2351 - 2354 2010年 [査読有り][通常論文]
  • Tatsuhiko Yoshino, Hiroyuki Morimoto, Gang Lu, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 131 47 17082 - + 2009年12月 [査読有り][通常論文]
     
    Construction of contiguous tetrasubstituted chiral carbon stereocenters via direct catalytic asymmetric aldol. reaction of a-substituted a-isothiocyanato esters with unactivated simple ketones is described. A Bu2Mg/Schiff base catalyst promoted the aldol addition/cyclization sequence at room temperature, giving protected alpha-amino-beta-hydroxy esters with contiguous tetrasubstituted chiral carbon stereocenters in 99 to 68% yield, 98:2 to 74:26 dr, and 98 to 82% ee.
  • Akitake Yamaguchi, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 131 31 10842 - + 2009年08月 [査読有り][通常論文]
     
    A Ba-catalyzed dynamic kinetic asymmetric transformation (DYKAT) involving a direct aldol/retro-aldol reaction of beta,gamma-unsaturated ester donors is described. A Ba(O-iPr)(2)/BINOL complex promoted the direct aldol reaction/isomerization sequence, and alpha-alkylidene-beta-hydroxy esters were obtained from aryl, heteroaryl, alkenyl, and alkyl aldehydes under simple proton-transfer conditions with 99-87% ee and > 20:1 to 15:1 alpha/gamma selectivity.
  • Masakatsu Shibasaki, Motomu Kanai, Shigeki Matsunaga, Naoya Kumagai
    ACCOUNTS OF CHEMICAL RESEARCH 42 8 1117 - 1127 2009年08月 [査読有り][通常論文]
     
    The concept of bifunctional catalysis, wherein both partners of a bimolecular reaction are simultaneously activated, is very powerful for designing efficient asymmetric catalysts. Catalytic asymmetric processes are indispensable for producing enantiomerically enriched compounds in modern organic synthesis, providing more economical and environmentally benign results than methods requiring stoichiometric amounts of chiral reagents. Extensive efforts in this field have produced many asymmetric catalysts, and now a number of reactions can be rendered asymmetric. We have focused on the development of asymmetric catalysts that exhibit high activity, selectivity, and broad substrate generality under mild reaction conditions. Asymmetric catalysts based on the concept of bifunctional catalysis have emerged as a particularly effective class, enabling simultaneous activation of multiple reaction components. Compared with conventional catalysts, bifunctional catalysts generally exhibit enhanced catalytic activity and higher levels of stereodifferentiation under milder reaction conditions, attracting much attention as next-generation catalysts for prospective practical applications. In this Account, we describe recent advances in enantioselective catalysis with bifunctional catalysts. Since our identification of heterobimetallic rare earth-alkali metal-BINOL (REMB) complexes, we have developed various types of bifunctional multimetallic catalysts. The REMB catalytic system is effective for catalytic asymmetric Corey-Chaykovsky epoxidation and cyclopropanation. A dinucleating Schiff base has emerged as a suitable multidentate ligand for bimetallic catalysts, promoting catalytic syn-selective nitro-Mannich, anti-selective nitroaldol, and Mannich-type reactions. The sugar-based ligand GluCAPO provides a suitable platform for polymetallic catalysts; structural elucidation revealed that their higher order polymetallic structures are a determining factor for their function in the catalytic asymmetric Strecker reaction. Rational design identified a related ligand, FujiCAPO, which exhibits superior performance in catalytic asymmetric conjugate addition of cyanide to enones and a catalytic asymmetric Diels-Alder-type reaction. The combination of an amide-based ligand with a rare earth metal constitutes a unique catalytic system: the ligand-metal association is in equilibrium because of structural flexibility. These catalytic systems are effective for asymmetric amination of highly coordinative substrate as well as for Mannich-type reaction of alpha-cyanoketones, in which hydrogen bonding cooperatively contributes to substrate activation and stereodifferentiation. Most of the reactions described here generate stereogenic tetrasubstituted carbons or quaternary carbons, noteworthy accomplishments even with modern synthetic methods. Several reactions have been incorporated into the asymmetric synthesis of therapeutics (or their candidate molecules) such as Tamiflu, AS-3201 (ranirestat), GRL-06579A, and ritodrine, illustrating the usefulness of bifunctional asymmetric catalysis.
  • Yuko Kato, Makoto Furutachi, Zhihua Chen, Harunobu Mitsunuma, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 131 26 9168 - + 2009年07月 [査読有り][通常論文]
     
    Catalytic asymmetric 1,4-additions of 3-substituted oxindoles to beta-aryl, beta-heteroaryl, and beta-alkenyl nitroalkenes are described. A new homodinuclear Mn-2(OAc)(2)-Schiff base 1 complex was required to realize high diastereo- and enantioselectivity. Mn-2(OAc)(2)-1 (1-5 mol %) promoted the 1,4-additions in 99-83% yield, 96-85% ee, and >30:1-5:1 dr at room temperature, providing useful chiral building blocks for the synthesis of beta-aminooxindoles with vicinal quaternary/tertiary carbon stereocenters.
  • Keiichi Hara, Shin-Ya Tosaki, Vijay Gnanadesikan, Hiroyuki Morimoto, Shinji Harada, Mari Sugita, Noriyuki Yamagiwa, Shigeki Matsunaga, Masakatsu Shibasaki
    TETRAHEDRON 65 26 5030 - 5036 2009年06月 [査読有り][通常論文]
     
    Full details of the kinetic resolution of tertiary nitroaldols derived from simple ketones are described. Mixed BINOL/biphenol La-Li heterobimetallic complexes gave the best selectivity in retro-nitroaldol reactions of racemic tertiary nitroaldols. Using a 2:1 mixture of La-Li-3-(binaphthoxide 1a)(3) complex (LLB) and La-Li-3-(biphenoxide 1e)(3) complex, chiral tertiary nitroaldols were obtained in 80-97% ee and 30-47% recovery yield. Transformations of products were also investigated. (C) 2009 Elsevier Ltd. All rights reserved.
  • Yuko Kato, Zhihua Chen, Shigeki Matsunaga, Masakatsu Shibasaki
    SYNLETT 10 1635 - 1638 2009年06月 [査読有り][通常論文]
     
    A catalytic asymmetric synthesis of nitrogen-containing gem-bisphoshonates is described. A Lewis acid-Bronsted base bifunctional homodinuclear Ni-2-Schiff base complex promoted catalytic enantioselective conjugate addition of nitroacetates to ethylidenebisphosphonates, giving products in up to 93% ee and 94% yield. Transformation of the product into a chiral alpha-amino ester with it gem-bisphosphonate moiety is also described.
  • Hisashi Mihara, Yingjie Xu, Nicholas E. Shepherd, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 131 24 8384 - + 2009年06月 [査読有り][通常論文]
     
    Development of a new heterobimetallic Ga(O-iPr)(3)/Yb(OTf)(3)/Schiff base 2d complex for catalytic asymmetric alpha-additions of isocyanides to aldehydes is described. Schiff base 2d derived from o-vanillin was suitable to utilize cationic rare earth metal triflates with good Lewis acidity in bimetallic Schiff base catalysis. The Ga(O-iPr)(3)/Yb(OTf)(3)/Schiff base 2d complex promoted asymmetric a-additions of alpha-isocyanoacetamides to aryl, heteroaryl, alkenyl, and alkyl aldehydes in good to excellent enantioselectivity (88-98% ee).
  • Toshihiko Sone, Gang Lu, Shigeki Matsunaga, Masakatsu Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 48 9 1677 - 1680 2009年 [査読有り][通常論文]
  • Zhihua Chen, Makoto Furutachi, Yuko Kato, Shigeki Matsunaga, Masakatsu Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 48 12 2218 - 2220 2009年 [査読有り][通常論文]
  • Yingjie Xu, Gang Lu, Shigeki Matsunaga, Masakatsu Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 48 18 3353 - 3356 2009年 [査読有り][通常論文]
  • Shinsuke Mouri, Zhihua Chen, Shigeki Matsunaga, Masakatsu Shibasaki
    CHEMICAL COMMUNICATIONS 34 5138 - 5140 2009年 [査読有り][通常論文]
     
    A homodinuclear Ni-2-Schi. base 1 complex (0.1-1 mol%) promoted the direct catalytic asymmetric aldol reaction of beta-keto esters with formaldehyde, giving hydroxymethylated adducts in 94-66% ee.
  • Hidetoshi Noda, Sean H. Wiedemann, Shigeki Matsunaga, Masakatsu Shibasaki
    CHEMISTRY LETTERS 37 11 1180 - 1181 2008年11月 [査読有り][通常論文]
     
    Stereoselective synthesis of functionalized pyrrolidines with all-carbon quaternary stereocenters is described. DYI3 catalyzed the ring opening of cyclopropanecarboxylate equivalents and promoted Mannich-type addition of the resulting alpha,alpha-disubstituted enolate intermediates to aryl and isomerizable alkyl imines, giving products in 86-58% yield and >96:4-84:16 diastereoselectivity.
  • Zhihua Chen, Kenichiro Yakura, Shigeki Matsunaga, Masakatsu Shibasaki
    ORGANIC LETTERS 10 15 3239 - 3242 2008年08月 [査読有り][通常論文]
     
    Direct catalytic asymmetric Mannich-type reactions beta-keto phosphonates are described. A homodinuclear Ni(2)-Schiff base complex promoted the reaction at 0 degrees C, giving beta-amino phosphonates in up to 90% yield, 20:1 dr, and 99% ee. Control experiments suggested that two Ni metals are important for achieving high yield and stereoselectivity.
  • Toshihiko Sone, Akitake Yamaguchi, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 130 31 10078 - + 2008年08月 [査読有り][通常論文]
     
    Catalytic asymmetric Corey-Chaykovsky epoxidation of ketones with dimethyloxosulfonium methylide 2 using an LLB 1a + Ar(3)P = O complex proceeded smoothly at room temperature, and 2,2-disubstituted termimal epoxides were obtained in high enantioselectivity (91-97%) and yield (> 88-99%) from a broad range of methyl ketones with 1-5 mol % catalyst loading. The use of achiral addictive Ar(3)P = O 5i was important to achieve high enantioselectivity.
  • Masakatsu Shibasaki, Shigeki Matsunaga, Naoya Kumagai
    SYNLETT 11 1583 - 1602 2008年07月 [査読有り][通常論文]
     
    Recent advances from Our group in the design and applications of multimetallic bifunctional asymmetric catalysts are described. Suitable design of chiral ligands and selection of metals were important to realize cooperative bimetallic catalysis. In this account, our strategies for constructing flexible and diverse chiral environments in multimetallic complexes for the rapid optimization of targeted reactions, Such as tertiary nitroaldol kinetic resolution, cyclopropanation of electron-deficient olefins, cyano-ethoxycarbonylation of aldehydes, direct Mannich-type reactions, the nitro-Mannich reaction, the anti-selective nitroaldol reaction, and amination, are discussed in detail.
  • Yamaguchi A, Matsunaga S, Shibasaki M
    Organic letters 10 11 2319 - 2322 2008年06月 [査読有り][通常論文]
     
    Direct catalytic asymmetric Mannich-type reactions of gamma-butenolides are described. A chiral Lewis acid/amine base/Bronsted acid combination was used to catalyze a gamma-addition of gamma-butenolides to N-diphenylphosphinoyl imines, affording the products in up to >99% yield, anti/syn = >97:3, and 84% ee. The use of a catalytic amount of TfOH in addition to La(OTf)(3)/Me-PyBox/TMEDA was important for improving yield and stereoselectivity.
  • Yoshihiro Sohtome, Yuko Kato, Shinya Handa, Naohiro Aoyama, Keita Nagawa, Shigeki Matsunaga, Masakatsu Shibasaki
    ORGANIC LETTERS 10 11 2231 - 2234 2008年06月 [査読有り][通常論文]
     
    Stereodivergent construction of three contiguous stereocenters in catalytic doubly diastereoselective nitroaldol reactions of a-chiral aldehydes with nitroacetaldehyde dimethyl acetal using two types of heterobimetallic catalysts is described. A La-Li-BINOL (LLB) catalyst afforded anti,syn-nitroaldol products in >20:1-14:1 selectivity, and a Pd/La/Schiff base catalyst afforded complimentary syn,syn-nitroaldol products in 10:1-5:1 selectivity.
  • Sean H. Wiedemann, Hidetoshi Noda, Shinji Harada, Shigeki Matsunaga, Masakatsu Shibasaki
    ORGANIC LETTERS 10 8 1661 - 1664 2008年04月 [査読有り][通常論文]
     
    A new catalytic aldol-type addition of cyclopropanecarboximides to aldehydes via iodide-mediated ring-opening is presented. The reaction was found to be catalyzed at 0 degrees C using either a Sc(OTf)(3)/Nal system or Scl(3). Stereoselective formation of alpha,alpha-disubstituted enolates occurred in situ. gamma-Lactams bearing alpha-carbonyl quaternary stereocenters were obtained in 97-57% yield, and dr = 90:10-80:20 after ring closure.
  • Zhihua Chen, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 130 7 2170 - + 2008年02月 [査読有り][通常論文]
     
    Catalytic asymmetric direct Mannich-type reactions of alpha-substituted nitroacetates using a new benchstable homodinuclear Ni(2)-Schiff base 1b complex are described. The Ni(2)-1b complex gave Mannich products, precursors for anti-alpha,beta-diamino acids with an alpha-tetrasubstituted carbon stereocenter, in >99-91 % ee. The Ni(2)-1b complex was also applicable to direct Mannich-type reactions of malonates and beta- keto ester, giving products in high stereoseleclivity (up to 99% ee, dr >97:3). Preliminary mechanistic studies suggested that the dinuclear Ni metal centers had key roles to achieve good reactivity and high stereoselectivity.
  • Takita R, Harada S, Ohshima T, Matsunaga S, Shibasaki M
    Organic Syntheses 85 118 - 130 2008年 [査読有り][通常論文]
  • Shigeki Matsunaga, Masakatsu Shibasaki
    BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 81 1 60 - 75 2008年01月 [査読有り][通常論文]
     
    Design and applications of multimetallic bifunctional asymmetric catalysts based on the proximity-effect-control concept are described. Suitable design of chiral ligands and selection of metals were important to realize cooperative bimetallic catalysis. Homo-multimetallic complexes, using linked-BINOLs (Zn, In, Y, and La), as well as hetero-multi-metallic complexes, using a dinucleating Schiff base, BINOL, and pybox (Cu-Sm, La-Li, and Y-Li), were developed for asymmetric direct aldol reactions, Michael reactions, direct Mannich-type reactions, nitro-Mannich-type reaction, aza-Michael reactions, kinetic resolution of tert-nitroaldols, and cyanation reactions. Synergistic effects of two or more metals played a key role in promoting the reactions in high reactivity and enantioselectivity.
  • Masataka Morita, Toshihiko Sone, Kenzo Yamatsugu, Yoshihiro Sohtome, Shigeki Matsunaga, Motomu Kanaia, Watanabe B. Yasuyoshi, Masakatsu Shibasaki
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 18 2 600 - 602 2008年01月 [査読有り][通常論文]
     
    A protocol applicable for the synthesis of an oseltamivir positron emission tomography (PET) tracer was developed. Acetylation of amine 3 with CH(3)COCl, followed by deprotection and aqueous workup, produced oseltamivir 4 from 3 within 10 min. The obtained 4 was sufficiently pure for PET studies. This method can be extended to PET tracer synthesis using CH(3)(11)COCl. (c) 2007 Elsevier Ltd. All rights reserved.
  • Hisashi Mihara, Yoshihiro Sohtome, Shigeki Matsunaga, Masakatsu Shibasaki
    CHEMISTRY-AN ASIAN JOURNAL 3 2 359 - 366 2008年 [査読有り][通常論文]
     
    Catalytic asymmetric synthesis of GRL-06579A (1), an HIV-1 protease inhibitor effective against multiprotease-inhibitor-resistant viruses, is described. A convergent strategy that utilizes heterobimetallic multifunctional catalysts developed in our group is a key feature of the synthesis. The chirality of the bicyclic tetrahydrofuran unit of 1 was introduced through Al-Li-bis(binaphthoxide) (ALB) catalyst-controlled Michael addition of dimethyl malonate to racemic 4-O-protected cyclopentenone. ALB afforded not only the trans adduct with up to 96 % ee from a matched substrate through kinetic resolution, but also the cis adduct with 99 % ee through a catalyst-controlled Michael addition to a mismatched substrate. The Michael addition to produce the unusual cis adduct is described in detail. The framework of the bicyclic tetrahydrofuran was constructed by an intramolecular oxy-Michael reaction. The amino alcohol unit was constructed by an La-Li-3-tris(binaphthoxide) (LLB)-catalyzed diastereoselective nitroaldol reaction of N-Boc aldehyde (Boc=tert-butoxycarbonyl) derived from L-phenylalanine. LLB promoted the nitroaldol reaction without racemization of the chiral aldehyde to give the nitroaldol adduct in 85% yield and with 93:7 diastereoselectivity and over 99 % ee.
  • Shinya Handa, Keita Nagawa, Yoshihiro Sohtome, Shigeki Matsunaga, Masakatsit Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 47 17 3230 - 3233 2008年 [査読有り][通常論文]
  • Keiichi Hara, So-Young Park, Noriyuki Yamagiwa, Shigeki Matsunaga, Masakatsu Shibasaki
    CHEMISTRY-AN ASIAN JOURNAL 3 8-9 1500 - 1504 2008年 [査読有り][通常論文]
     
    A rare-earth-metal-catalyzed asymmetric epoxidation of alpha,beta-unsaturated phosphane oxides is described. The appropriate selection of a chiral ligand and an achiral additive is important for achieving good reactivity and enantioselectivity. A Y(O-iPr)(3)/biphenyldiol complex with an achiral phosphane oxide additive afforded beta-aryl alpha,beta-epoxy phosphane oxides in 77-99% yield and with 96-98% ee. With beta-alkyl substrates, the reaction proceeded smoothly in the absence of an achiral additive, and beta-alkyl alpha,beta-epoxy phosphane oxides were obtained in 94-99% yield and with 87-95 % ee.
  • Gang Lu, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 47 36 6847 - 6850 2008年 [査読有り][通常論文]
  • Morimoto H, Yoshino T, Yukawa T, Lu G, Matsunaga S, Shibasaki M
    Angewandte Chemie (International ed. in English) 47 47 9125 - 9129 2008年 [査読有り][通常論文]
  • Hiroyuki Kakei, Toshihiko Sone, Yoshihiro Sohtome, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 129 44 13410 - 13411 2007年11月 [査読有り][通常論文]
  • Naoya Kumagai, Shigeki Matsunaga, Masakatsu Shibasaki
    TETRAHEDRON 63 35 8598 - 8608 2007年08月 [査読有り][通常論文]
     
    The development of an efficient catalytic system for the direct addition of acetonitrile under mild amine basic conditions is described. A cooperative catalysis of CpRu complex, DBU, and NaPF6 enables chemoselective and catalytic generation of nucleophiles from barely acidic acetonitrile, which is integrated into the addition to aldehydes, imines, and activated ketones. Mechanistic investigations revealed that the three catalyst components work together to achieve high catalytic efficiency. (c) 2007 Elsevier Ltd. All rights reserved.
  • Hiroyuki Morimoto, Gang Lu, Naohiro Aoyama, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 129 31 9588 - + 2007年08月 [査読有り][通常論文]
     
    Direct catalytic asymmetric Mannich-type reaction of a trichloromethyl ketone as a propionate equivalent donor is described. A new lanthanum aryloxide-iPr-pybox + lithium aryloxide combined catalyst was the most effective, promoting the reaction of N-2-thiophenesulfonyl imines with the trichloromethyl ketone. syn-Mannich adducts were obtained from various aryl, heteroaryl, alkenyl, and alkyl imines in > 99-72% yield, syn/anti of > 30:1-8:1, and 98-92% ee (from a propionate equivalent donor) using 2.5-10 mol % catalyst. The Mannich adduct was converted not only into ester but also into useful building blocks.
  • Akitake Yamaguchi, Naohiro Aoyama, Shigeki Matsunaga, Masakatsu Shibasaki
    ORGANIC LETTERS 9 17 3387 - 3390 2007年08月 [査読有り][通常論文]
     
    Barium-catalyzed direct Mannich-type reactions of a beta,gamma-unsaturated ester are described. The Ba-catalyst not only promoted the Mannich-type reactions, but also isomerized Mannich adducts to afford beta-methyl aza-Morita-Baylis-Hillman-type products in 61-88% yield from various aryl, heteroaryl, and alkyl imines. Preliminary trials on enantioselective variants with a chiral biaryldiol ligand gave products in up to 80% ee.
  • So-Young Park, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki
    TETRAHEDRON LETTERS 48 16 2815 - 2818 2007年04月 [査読有り][通常論文]
     
    Catalytic asymmetric Michael reactions of a malonate to acyclic alpha,beta-unsaturated N-acylpyrroles as ester equivalent acceptors are described. A La(O-iPr)(3)/(S,S)-linked-BINOL complex, which is suitable for Michael addition to cyclic enones, is not suitable for acyclic a,p-unsaturated N-acylpyrroles. A new (S,S)-Ph-linked-BINOL chiral ligand was developed to improve enantioselectivity, and a La(O-iPr)(3)/(S,S)-Ph-linked-BINOL complex with the addition of HFIP afforded Michael adducts in good yield and enantioselectivity (up to 96% ee). (c) 2007 Elsevier Ltd. All rights reserved.
  • Shinya Handa, Vijay Gnanadesikan, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 129 16 4900 - + 2007年04月 [査読有り][通常論文]
     
    syn-Selective catalytic asymmetric nitro-Mannich reactions using a heterobimetallic Cu/Sm/Schiff base complex are described. The present method is complementary to the previously reported methods, and products were obtained in high syn-selectivity (> 20:1), yield (99-62%), and enantioselectivity (98-83% ee). Both Cu and Sm metals, aligned suitably in a dinucleating Schiff base ligand, were essential to realize high synselectivity.
  • Shinji Harada, Ryo Takita, Takashi Ohshima, Shigeki Matsunaga, Masakatsu Shibasaki
    CHEMICAL COMMUNICATIONS 9 948 - 950 2007年03月 [査読有り][通常論文]
     
    Indium(III)-catalyzed asymmetric alkynylation of aryl, heteroaryl, alkyl and alkenyl aldehydes with 2-methyl-3-butyn-2-ol as an ethyne equivalent donor was realized, and products were obtained in moderate to good yields (up to 97%) and high enantioselectivities (up to 99% ee) using 2-10 mol% of catalyst.
  • Hiroyuki Kakei, Riichiro Tsuji, Takashi Ohshima, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki
    CHEMISTRY-AN ASIAN JOURNAL 2 2 257 - 264 2007年 [査読有り][通常論文]
     
    ne full details of the asymmetric epoxidation of alpha,beta-unsaturated esters catalyzed by yttrium complexes with biaryldiol ligands are described. An yttrium-biphenyldiol catalyst, generated from Y(OiPr)(3)-biphenyldiol ligand-triphenylarsine oxide (1:1:1), is suitable for the epoxidation of various alpha,beta-unsaturated esters. With this catalyst, beta-aryl cc,p-unsaturated esters gave high enantioselectivities and good yields (<= 99% ee). ne reactivity of this catalyst is good, and the catalyst loading could be decreased to as little as 0.5-2 mol % (the turnover number was up to.116), while high enantiomeric excesses were maintained. For beta- alkyl alpha,beta-unsaturated esters, an yttrium-binot catalyst, generated from Y(OiPr)(3)-binol ligand-triphenylphosphine oxide (1:1:2), gave the best enantioselectivities (<= 97% ee). The utility of the epoxidation reaction was demonstrated in an efficient synthesis of (-)-ragaglitazar, a potential antidiabetes agent.
  • Hongbo Qin, Noriyuki Yamagiwa, Shigeki Matsunaga, Masakatsu Shibasaki
    CHEMISTRY-AN ASIAN JOURNAL 2 1 150 - 154 2007年 [査読有り][通常論文]
     
    Catalytic intermolecular hydroamination of vinyl arenes is described. Our initial investigation revealed that a Bi(OTf)(3)/[CU(CH3CN)(4)]PF6 system previously developed for catalytic intermolecular hydroamination of 1,3-dienes was suitable for hydroamination of a styrene with sulfonamides, but the substrate generality of this system was unsatisfactory. Several-metals were screened to expand the substrate scope, and a new Hf(OTf)(4)/[CU(CH3CN)(4)]PF6 System was determined to be highly suitable. The combination of Hf(OTf)(4) and [Cu-(CH3CN)(4)]PF6 efficiently promoted the hydroamination of various vinyl arenes, including less-reactive vinyl arenes with electron-withdrawing groups. This strategy was applied to sulfonamides, carbamates, and carboxamides, and products were obtained in up to 99% yield with 0.3-10 mol% catalyst loading.
  • Hongbo Qin, Noriyuki Yamagiwa, Shigeki Matsunaga, Masakatsu Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 46 3 409 - 413 2007年 [査読有り][通常論文]
  • Shigeki Matsunaga, Mari Sugita, Noriyuki Yamagiwa, Shinya Handa, Akitake Yamaguchi, Masakatsu Shibasaki
    BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 79 12 1906 - 1912 2006年12月 [査読有り][通常論文]
     
    Full details of syn-selective catalytic asymmetric direct Mannich-type reactions of aromatic and heteroaromatic hydroxy ketones promoted by Y[N(SiMe3)(2)](3)/linked-BINOL complexes are described. From a screening of various rare-earth metals and linked-BINOL derivatives, a Y[N(SiMe3)(2)](3)/TMS-linked-BINOL (1.7/1) complex was determined to be the most effective. Mannich-type reactions of aromatic and heteroaromatic hydroxy ketones with aryl and alkenyl N-dipheny]phosphinoylimines, catalyzed by 0.1 molar amount of Y[N(SiMe3)(2)](3) and 0.059 molar amount of TMS-linked-BINOL, afforded syn-beta-amino-alpha-hydroxy ketones in good yields (78-98%), high diastereoselectivity (syn/anti = 81/19-96/4), and high enantioselectivity (86-98% ee).
  • Zhihua Chen, Hiroyuki Morimoto, Shigeki Matsunaga, Masakatsu Shibasaki
    SYNLETT 20 3529 - 3532 2006年12月 [査読有り][通常論文]
     
    Catalytic asymmetric epoxidation of a-methyl alpha,beta-unsaturated carboxylic acid derivatives was achieved using anilide as a template. The Pr(Oi-Pr)(3)-6,6'-Ph-BINOL complex (10 mol%) with a Ph3P(O) (30 mol%) additive promoted the epoxidation of anilides in up to 99% yield and 88% ee. For alpha-methyl-beta-Ph alpha,beta-unsaturated anilide, the Gd(Oi-Pr)(3)-6,6'-I-BINOL complex (10 mol%) with Ar3P(O) (30 mol%, Ar = 4-methoxyphenyl) was suitable, giving epoxide in 87% yield and 78% ee.
  • Shin-ya Tosaki, Keiichi Hara, Vijay Gnanadesikan, Hiroyuki Morimoto, Shinji Harada, Mari Sugita, Noriyuki Yamagiwa, Shigeki Matsunaga, Masakatsu Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 128 36 11776 - 11777 2006年09月 [査読有り][通常論文]
  • Shigeki Matsunaga
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 64 7 778 - 779 2006年07月 [査読有り][通常論文]
     
    This mini review focuses on the recent advances in catalytic intermolecular hydroaminations: Pd-, Ni-, Rh-, and Ru-catalyzed addition reactions of amine to olefins, and their mechanistic insights are described concisely. Oxidative addition of ammonia to an Ir complex to activate the N-H bond is mentioned as well, that is a milestone achievement toward the intermolecular hydroamination using ammonia as a nitrogen source.
  • S Matsunaga, H Qin, M Sugita, S Okada, T Kinoshita, N Yamagiwa, M Shibasaki
    TETRAHEDRON 62 28 6630 - 6639 2006年07月 [査読有り][通常論文]
     
    Catalytic asymmetric epoxidation of alpha,beta-unsaturated N-acylpyrroles as monodentate and activated ester equivalent acceptors is described. A Sm(O-i-Pr)(3)/(R)-H-8-BINOL complex promoted the epoxidation reaction to afford products in high yield (up to quant) and high enantiornefic excess (up to > 99.5% ee). Reaction proceeded smoothly using cumene hydroperoxide (CMHP) with low explosive hazard, and completed within 0.2-0.5 h with 5 mol % catalyst. Catalyst loading was successfully reduced to as little as 0.02 mol %. The N-acylpyrrole properties as well as efficient synthesis of oc, -unsaturated N-acylpyrroles are also described. (c) 2006 Elsevier Ltd. All rights reserved.
  • 松永 茂樹
    有機合成化学協会誌 : JOURNAL OF Synthetic Organic Chemistry JAPAN 64 7 778 - 779 The Society of Synthetic Organic Chemistry, Japan 2006年07月01日 [査読無し][通常論文]
     
    This mini review focuses on the recent advances in catalytic intermolecular hydroaminations : Pd-, Ni-, Rh-, and Ru-catalyzed addition reactions of amine to olefins, and their mechanistic insights are described concisely. Oxidative addition of ammonia to an Ir complex to activate the N-H bond is mentioned as well, that is a milestone achievement toward the intermolecular hydroamination using ammonia as a nitrogen source.
  • Akitake Yamaguchi, Shigeki Matsunaga, Masakatsu Shibasaki
    TETRAHEDRON LETTERS 47 24 3985 - 3989 2006年06月 [査読有り][通常論文]
     
    A direct catalytic asymmetric Mannich-type reaction of isomerizable aliphatic imines is described. A Et2Zn/(S,S)-linked-BINOL complex was suitable for chemoselective enolate formation from a hydroxyketone in the presence of isomerizable aliphatic N-diphenylphosphinoyl imines. The reaction proceeds smoothly and beta-alkyl-beta-amino-alpha-hydroxyketones were obtained in good yield and high enantioselectivity (up to 99% ee), albeit in modest to low diastereoselectivity. (c) 2006 Elsevier Ltd. All rights reserved.
  • M Shibasaki, S Matsunaga
    JOURNAL OF ORGANOMETALLIC CHEMISTRY 691 10 2089 - 2100 2006年05月 [査読有り][通常論文]
     
    Development of metal/linked-BINOL complexes and their applications in direct catalytic asymmetric Mannich-type reactions of hydroxyketones are reviewed. A Et2Zn/linked-BINOL complex was effective for diastereo- and enantioselective synthesis of beta-amino alcohols. By choosing the proper protective groups on the imine nitrogen, either anti- or syn-beta-amino alcohol was obtained in excellent enantioselectivity (up to > 99.5% ee) using the same zinc catalysis. Y{N(SiMe3)(2)}(3)/linked-BINOL complex was effective for various hydroxyketones, affording syn-beta-amino alcohols with high enantioselectivity (up to 98% ee). To broaden the nucleophile scope to carboxylic acid derivatives, N-acylpyrrole was utilized as an ester equivalent donor. In(O-iPr)(3)/linked-BINOL complex was effective for generating an In-enolate from N-acylpyrrole in situ, giving Mannich adducts with high enantioselectivity (up to 98% ee). (c) 2005 Elsevier B.V. All rights reserved.
  • HB Qin, N Yamagiwa, S Matsunaga, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 128 12 4162 - 4162 2006年03月 [査読有り][通常論文]
  • N Yamagiwa, Y Abiko, M Sugita, J Tian, S Matsunaga, M Shibasaki
    TETRAHEDRON-ASYMMETRY 17 4 566 - 573 2006年02月 [査読有り][通常論文]
     
    A highly enantioselective cyano-phosphorylation of aldehydes catalyzed by a YLi(3)tris(binaphtlioxide) complex YLB 1 is described. The slow addition of diethyl cyanophosphonate 4 to aldehydes 5 in the presence of YLB 1 (10 mol %), H2O (30 mol %), tris(2,6-dimethoxyplienyl)phosphine oxide 3a (10 mol %), and BuLi (10 mol %) afforded cyanohydrin O-phosphates 6 in up to 98% yield and 97% ee. Mechanistic studies revealed that the addition of cyanide to aldehydes is irreversible and determines the enantioselectivity. The reaction mechanism is also discussed in detail. (c) 2006 Elsevier Ltd. All rights reserved.
  • H Qin, N Yamagiwa, S Matsunaga, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 128 5 1611 - 1614 2006年02月 [査読有り][通常論文]
     
    A Bi(OTf)(3)/Cu(CH3CN)(4)PF6 system efficiently promoted intermolecular 1:1 hydroamination of 1,3-dienes with various carbamates, sulfonamides, and carboxamides to afford allylic amines in good yield (up to 96%). Reaction proceeded with 0.5-10 mol % catalyst loading at 25-100 degrees C (generally at 50 degrees C) in 1,4-dioxane within 24 h. The Bi(OTf)(3)/Cu(CH3CN)(4)PF6 system constitutes a new entry into series of intermolecular hydroamination catalysis. Mechanistic studies and the postulated reaction mechanism are also discussed.
  • M Shibasaki, M Kanai, S Matsunaga
    ALDRICHIMICA ACTA 39 2 31 - 39 2006年 [査読有り][通常論文]
  • M Shibasaki, S Matsunaga
    CHEMICAL SOCIETY REVIEWS 35 3 269 - 279 2006年 [査読有り][通常論文]
     
    The design and application of linked-BINOLs investigated in our group are reviewed. Linked-BINOLs are a kind of semi-crown ether, thus they are flexible and applicable to metals having various ionic radii (Ga3+, Li+, Zn2+, In3+, La3+, and Y3+). The flexible linker segment, containing a coordinative heteroatom, has a crucial role in the construction of a unique and effective chiral environment that is not accessible from BINOL itself. Applications of linked-BINOLs to an epoxide opening reaction, Michael reactions, a direct aldol reaction, direct Michael reactions of a hydroxyketone, and direct Mannich-type reactions of hydroxyketones and N-acylpyrrole are described.
  • Hiroyuki Morimoto, Seat H. Wiedemann, Akitake Yamaguchi, Shinji Harada, Zhihua Chen, Shigeki Matsunaga, Masakatsu Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 45 19 3146 - 3150 2006年 [査読有り][通常論文]
  • M Sugita, A Yamaguchi, N Yamagiwa, S Handa, S Matsunaga, M Shibasaki
    ORGANIC LETTERS 7 23 5339 - 5342 2005年11月 [査読有り][通常論文]
     
    Chiral Y{N(SiMe3)(2)}(3)/linked-BINOL catalyst generated Y-enolate in situ from various hydroxyketones (R-2 = aryl, heteroaryl).beta-Amino-alpha-hydroxy ketones (R-1 = aryl, heteroaryl, alkenyl) were obtained syn-selectively (up to 96/4) in high ee (up to 98%) and good yield (up to 98% yield).
  • N Yamagiwa, HB Qin, S Matsunaga, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 127 38 13419 - 13427 2005年09月 [査読有り][通常論文]
     
    The full details of a catalytic asymmetric aza-Michael reaction of methoxylamine promoted by rare earth-alkali metal heterobimetallic complexes are described, demonstrating the effectiveness of Lewis acid-Lewis acid cooperative catalysis. First, enones were used as substrates, and the 1,4-adducts were obtained in good yield (57-98%) and high ee (81-96%). Catalyst loading was successfully reduced to 0.3-3 mol % with enones. To broaden the substrate scope of the reaction to carboxylic acid derivatives, alpha,beta-unsaturated N-acylpyrroles were used as monodentate, carboxylic acid derivatives. With beta-alkylsubstituted N-acylpyrroles, the reaction proceeded smoothly and the products were obtained in high yield and good ee. Transformation of the 1,4-adducts from enones and alpha,beta-unsaturated N-acylpyrroles afforded corresponding chiral aziridines and beta-amino acids. Detailed mechanistic studies, including kinetics, NMR analysis, nonlinear effects, and rare earth metal effects, are also described. The Lewis acid-Lewis acid cooperative mechanism, including the substrate coordination mode, is discussed in detail.
  • N Yamagiwa, J Tian, S Matsunaga, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 127 10 3413 - 3422 2005年03月 [査読有り][通常論文]
     
    Full details of a catalytic asymmetric cyano-ethoxycarbonylation reaction promoted by a heterobimetallic YLi(3)tris(binaphthoxide) complex (YLB 1), especially mechanistic studies, are described. In the cyanation reaction of aldehydes with ethyl cyanoformate, three achiral additives, H2O, tris(2,6-dimethoxyphenyl)phosphine oxide (3a), and BuLi, were required to achieve high reactivity and enantio-selectivity (up to > 99% yield and up to 98% ee). The roles of achiral additives and the reaction pathway were investigated in detail. In situ IR analysis revealed that the initiation step to generate LiCN from H2O, BuLi, and ethyl cyanoformate is rather slow. On the basis of mechanistic studies of the initiation step to generate an active nucleophilic species, reaction conditions were optimized by using a catalytic amount of acetone cyanohydrin as an initiator. Under the optimized conditions, the induction period decreased and the reaction completed within 9 min using 5 mol % YLB at -78 degrees C. Catalyst loading was successfully reduced to 1 mol %. Kinetic experiments and evaluation of the substituent effects,of phosphine oxide revealed that phosphine oxide had beneficial effects on both the reaction rate and the enantioselectivity. The putative active species as well as the catalytic cycle of the reaction are also discussed.
  • T Yoshida, H Morimoto, N Kumagai, S Matsunaga, M Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 44 22 3470 - 3474 2005年 [査読有り][通常論文]
  • S Harada, S Handa, S Matsunaga, M Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 44 28 4365 - 4368 2005年 [査読有り][通常論文]
  • N Kumagai, S Matsunaga, M Shibasaki
    CHEMICAL COMMUNICATIONS 28 3600 - 3602 2005年 [査読有り][通常論文]
     
    The cooperative catalysis of CpRu( PPh3)(2)( CH3CN) PF6 ( 1b) and DBU enables chemoselective nucleophilic activation of acetonitrile in the presence of base-sensitive aldehydes 2 to afford corresponding beta-hydroxynitriles 3 in good yield.
  • Y Abiko, N Yamagiwa, M Sugita, J Tian, S Matsunaga, M Shibasaki
    SYNLETT 13 2434 - 2436 2004年11月 [査読有り][通常論文]
     
    A highly enantioselective cyano-phosphorylation of aldehydes catalyzed by YLi(3)tris(binaphthoxide) complex (YLB, 1) is described. Slow addition of diethyl cyanophosphonate (4) to aldehydes 5 in the presence of 1 (10 mol%), H2O (30 mol%), tris(2,6-dimetboxyphenyl)phosphine oxide (10 mol%, 3a), and BuLi (10 mol%) afforded cyanohydrin O-phosphates 6 in up to 98% yield and 97% ee.
  • N Kumagai, S Matsunaga, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 126 42 13632 - 13633 2004年10月 [査読有り][通常論文]
  • S Matsunaga, T Yoshida, H Morimoto, N Kumagai, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 126 28 8777 - 8785 2004年07月 [査読有り][通常論文]
     
    Full details of a direct catalytic asymmetric Mannich-type reaction of a hydroxyketone using a Et2Zn/(S,S)-linked-BINOL complex are described. By choosing the proper protective groups on imine nitrogen, either anti- or syn-beta-amino alcohol was obtained in good diastereomeric ratio, yield, and excellent enantiomeric excess using the same zinc catalysis. N-Diphenylphosphinoyl (Dpp) imine 3 gave anti-beta-amino alcohols in anti/syn = up to >98/2, up to >99% yield, and up to >99.5% ee, while Boc-imine 4 gave syn-beta-amino alcohols in anti/syn = up to 5/95, up to >99% yield, and up to >99.5% ee. The high catalyst turnover number (TON) is also noteworthy. Catalyst loading was successfully reduced to 0.02 mol % (TON = up to 4920) for the anti-selective reaction and 0.05 mol % (TON = up to 1760) for the syn-selective reaction. The Et2Zn/(S,S)-linked-BINOL complex exhibited far better TON than in previous reports of catalytic asymmetric Mannich-type reactions. Mechanistic studies to clarify the reason for the high catalyst efficiency as well as transformations of Mannich adducts are also described.
  • S Matsunaga, T Kinoshita, S Okada, S Harada, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 126 24 7559 - 7570 2004年06月 [査読有り][通常論文]
     
    Synthesis and application of alpha,beta-unsaturated N-acylpyrroles as highly reactive, monodentate ester surrogates in the catalytic asymmetric epoxidation and Michael reactions are described. alpha,beta-Unsaturated N-acylpyrroles with various functional groups were synthesized by the Wittig reaction using ylide 2. A Sm(O-i-Pr)(3)/H-8-BINOL complex was the most effective catalyst for the epoxidation to afford pyrrolyl epoxides in up to 100% yield and >99% ee. Catalyst loading was successfully reduced to as little as 0.02 mol % (substrate/catalyst = 5000). The high turnover frequency and high volumetric productivity of the present reaction are also noteworthy. In addition, a sequential Wittig olefination-catalytic asymmetric epoxidation reaction was developed, providing efficient one-pot access to optically active epoxides from various aldehydes in high yield and ee (96-->99%). In a direct catalytic asymmetric Michael reaction of hydroxyketone promoted by the Et2Zn/linked-BINOL complex, Michael adducts were obtained in good yield (74-97%), dr (69/31-95/5), and ee (73-95%). This represents the first direct catalytic asymmetric Michael reaction of unmodified ketone to an alpha,beta-unsaturated carboxylic acid derivative. The properties of alpha,beta-unsaturated N-acylpyrrole are also discussed. Finally, the utility of the N-acylpyrrole unit for further transformations is demonstrated.
  • N Kumagai, S Matsunaga, M Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 43 4 478 - 482 2004年 [査読有り][通常論文]
  • N Yamagiwa, S Matsunaga, M Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 43 34 4493 - 4497 2004年 [査読有り][通常論文]
  • N Yamagiwa, S Matsunaga, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 125 52 16178 - 16179 2003年12月 [査読有り][通常論文]
  • J Tian, N Yamagiwa, S Matsunaga, M Shibasaki
    ORGANIC LETTERS 5 17 3021 - 3024 2003年08月 [査読有り][通常論文]
     
    graphic An efficient two-step conversion of alpha,beta-unsaturated aldehydes into optically active gamma-oxy-alpha,beta-unsaturated nitriles is described. First, catalytic asymmetric cyanation-ethoxycarbonylation using (S)-YLi(3)tris(binaphthoxide) (YLB) afforded chiral allylic cyanohydrin carbonate. Second, a [3,3]-sigmatropic rearrangement proceeded without racemization under thermal conditions to give gamma-oxy-alpha,beta-unsaturated nitriles. Lewis acids were also effective for the rearrangement, and the reaction proceeded smoothly under mild conditions. To demonstrate the utility of the conversion, concise catalytic enantioselective total synthesis of (+)-patulolide C was performed.
  • Y Suto, N Kumagai, S Matsunaga, M Kanai, M Shibasaki
    ORGANIC LETTERS 5 17 3147 - 3150 2003年08月 [査読有り][通常論文]
     
    A copper fluoride-catalyzed cyanomethylation that can be applied to a wide range of ketones and aldehydes was developed using TMSCH2-CN as a nucleophile. The reaction was extended to a conceptually more advanced copper alkoxide-catalyzed direct addition of alkylnitriles to aldehydes, which can act as a surrogate direct catalytic aldol reaction of esters. These reactions can be applied to the first catalytic enantioselective cyanomethylation of ketones and direct catalytic enantioselective cyanomethylation of aldehydes.
  • S Matsunaga, N Kumagai, S Harada, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 125 16 4712 - 4713 2003年04月 [査読有り][通常論文]
  • S Harada, N Kumagai, T Kinoshita, S Matsunaga, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 125 9 2582 - 2590 2003年03月 [査読有り][通常論文]
     
    Full details of our direct Michael addition of unmodified ketones using new asymmetric zinc catalysis are described. Et2Zn/(S,S)-linked-BINOL complexes were successfully applied to direct 1,4-addition reactions of hydroxyketones. The first generation Et2Zn/(S,S)-linked-BINOL 1 = 2/1 system was effective for 1,4-addition of 2-hydroxy-2'-methoxyacetophenone (3). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et2Zn, we found that a 1,4-addition reaction of beta-unsubstituted enone proceeded smoothly at 4 degreesC to afford products in high yield (up to 90%) and enantiomeric excess (up to 95%). In the case of beta-substituted enones, however, the first generation Et2Zn/(S,S)-linked-BINOL 1 = 2/1 system was not at all effective. The second generation Et2Zn/(S, S)-linked-BINOL 1 = 4/1 with MS 3A system was developed and was effective for various beta-substituted enones to afford products in good dr, yield (up to 99%), and high enantiomeric excess (up to 99% ee). With the Et2Zn/1 = 4/1 systems, catalyst loading for beta-unsubstituted enone was reduced to as little as 0.01 mol % (substrate/chiral ligand = 10 000). The new system was also effective for 1,4-addition reactions of 2-hydroxy-2'-methoxypropiophenone (9) to afford chiral tert-alcohol in high enantiomeric excess (up to 96% ee). Mechanistic investigations as well as transformations of the Michael adducts into synthetically versatile intermediates are also described.
  • N Kumagai, S Matsunaga, T Kinoshita, S Harada, S Okada, S Sakamoto, K Yamaguchi, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 125 8 2169 - 2178 2003年02月 [査読有り][通常論文]
     
    Full details of our newly developed catalyses with asymmetric zinc complexes as mimics of class II zinc-containing aldolase are described. A Et2Zn/(S,S)-linked-BlNOL complex was developed and successfully applied to direct catalytic asymmetric aldol reactions of hydroxyketones. A Et2Zn/(S,S)-linked-BINOL 1 = 2/1 system was initially developed, which efficiently promoted the direct aldol reaction of 2-hydroxy-2'-methoxyacetophenone (7d). Using 1 mol % of (S,S)-linked-BINOL I and 2 mol % of Et2Zn, we obtained 1,2-dihydroxyketones syn-selectively in high yield (up to 95%), good diastereomeric ratio (up to 97/3), and excellent enantiomeric excess (up to 99%). Mechanistic investigation of Et2Zn/(S,S)-linked-BINOL 1, including X-ray analysis, NMR analysis, cold spray ionization mass spectrometry (CSI-MS) analysis, and kinetic studies, provided new insight into the active oligomeric Zn/(S,S)-linked-BlNOL 1/ketone 7d active species. On the basis of mechanistic investigations, a modified second generation Et(2)Znl(SS)linked-BINOL 1 = 4/1 with molecular sieves 3A (MS 3A) system was developed as a much more effective catalyst system for the direct aldol reaction. As little as 0.1 mol % of (S, S)-linked-BINOL 1 and 0.4 mol % of Et2Zn promoted the direct aldol reaction smoothly, using only 1.1 equiv of 7d as a donor (substrate/ ligand = 1000). This is the most efficient, in terms of catalyst loading, asymmetric catalyst for the direct catalytic asymmetric aldol reaction. Moreover, the Et2Zn/(S,S)-linked-BlNOL 1 = 4/1 system was effective in the direct catalytic asymmetric aldol reaction of 2-hydroxy-2'-methoxypropiophenone (112), which afforded a chiral tetrasubstituted carbon center (tert-alcohol) in good yield (up to 97%) and ee (up to 97%), albeit in modest syn-selectivity. Newly developed (SS)-sulfur-linked-BINOL 2 was also effective in the direct aldol reaction of 12. The Et2Zn/(S,S)-sulfur-linked-BlNOL 2 = 4/1 system gave aldol adducts anti-selectively in good ee (up to 93%). Transformations of the aldol adducts into synthetically versatile intermediates were also described.
  • T Kinoshita, S Okada, Park, SR, S Matsunaga, M Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 42 38 4680 - 4684 2003年 [査読有り][通常論文]
  • S Matsunaga, T Ohshima, M Shibasaki
    ADVANCED SYNTHESIS & CATALYSIS 344 1 3 - 15 2002年01月 [査読有り][通常論文]
     
    The development and application of a novel linked-1,1'-binaphthol (linked-BINOL) as an approach towards practical asymmetric multifunctional catalysis is described. Linked-BINOL was first designed to increase the stability of a Ga-Li-BINOL complex against ligand exchange with 4-methoxyphenol. An oxygen-containing linked-BINOL, which is a semi crown ether, was effective in both promoting the formation of a monomer complex and increasing the stability of the Ga-Li complex. A Ga-Li-linked-BINOL complex promoted the epoxide opening reaction in up to 96% enantiomeric excess (ee). Second, based on the X-ray structural information of the Ga-Li-linked-BINOL complex, we designed a more stable lanthanide linked-BINOL complex. An air-stable, storable, and reusable La-linked-BINOL complex promoted the Michael reaction in up to >99% ee. The catalyst activity remained unchanged after storage under air for 4 weeks. Calculations suggested that the linked-BINOL would function as a pentadentate ligand in a lanthanum complex, thus efficiently improving the stability of the complex. Finally, the linked-BINOL was applied to a new homobimetallic multifunctional catalysis. A dinuclear Zn-Zn-linked-BINOL complex promoted the enantio- and diastereoselective direct aldol reaction in up to 99% ee, where one Zn cation might function as a Lewis acid and the other Zn-phenoxide as a Bronsted base.
  • J Tian, N Yamagiwa, S Matsunaga, M Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 41 19 3636 - 3638 2002年 [査読有り][通常論文]
  • J Tian, N Yamagiwa, S Matsunaga, M Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 41 19 3636 - 3638 2002年 [査読有り][通常論文]
  • N Kumagai, S Matsunaga, M Shibasaki
    ORGANIC LETTERS 3 26 4251 - 4254 2001年12月 [査読有り][通常論文]
     
    [GRAPHICS] 1,4-Addition (Michael addition) of 2-hydroxy-2'-methoxyacetophenone (2) to various alpha,beta -unsaturated ketones was efficiently promoted by a bimetallic Zn-Zn-linked-BINOL complex 3 with good yield (up to 90%) and excellent enantiomeric excess (up to 99% ee). The resulting 2-hydroxy-1,5-diketones were successfully converted to synthetically more versatile esters and amides.
  • N Kumagai, S Matsunaga, N Yoshikawa, T Ohshima, M Shibasaki
    ORGANIC LETTERS 3 10 1539 - 1542 2001年05月 [査読有り][通常論文]
     
    [GRAPHICS] The direct catalytic enantio and diastereoselective aldol reaction with 2-hydroxy-2 ' -methoxyacetophenone proceeded smoothly using as little as 1 mol % of a dinuclear zinc catalyst, Zn-Zn-linked BINOL complex 2, to afford alpha,beta -dihydroxy ketones in a highly syn-selective manner (up to synlanti 97/3) and in excellent yields (up to 95%) and ees (up to 99%), Efficient transformations of the alpha,beta -dihydroxy ketone into an alpha,beta -dihydroxy ester and an alpha,beta -dihydroxy amide via regioselective rearrangements are also described.
  • N Yoshikawa, N Kumagai, S Matsunaga, G Moll, T Ohshima, T Suzuki, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 123 16 3856 - 3856 2001年04月 [査読有り][通常論文]
  • N Yoshikawa, N Kumagai, S Matsunaga, G Moll, T Ohshima, T Suzuki, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 123 10 2466 - 2467 2001年03月 [査読有り][通常論文]
  • H Nogami, S Matsunaga, M Kanai, M Shibasaki
    TETRAHEDRON LETTERS 42 2 279 - 283 2001年01月 [査読有り][通常論文]
     
    The JandaJEL(TM)-supported bifunctional catalyst 3 (10 mol%) promoted the Strecker-type reaction of aromatic and alpha,beta -unsaturated imines in excellent yields with 83-87% ee in the presence of (BuOH)-Bu-t (110 mol%). The reactivity of 3 was comparable to the homogeneous analogue 1, and 3 could be recycled at least four times. (C) 2000 Elsevier Science Ltd. All rights reserved.
  • 大嶋 孝志, 許 佑君, 金 潤植, 松永 茂樹, 大堀 健, 柴崎 正勝
    天然有機化合物討論会講演要旨集 42 145 - 150 天然有機化合物討論会 2000年10月01日 
    Strychnine (1) is a representative member of the Strychnos family of indole alkaloids and has been a target of several synthetic investigations. In recent years, three research groups have culminated their research in the asymmetric total synthesis of (-)-1. To date, however, no catalytic asymmetric synthesis has been accomplished except for enzymatic method. We describe herein the development toward a novel stable, storable and reusable asymmetric catalyst (R,R)-La-linked-BINOL 10 and our synthetic studies of (-)-strychnine (1) employing catalytic asymmetric Michael reaction catalyzed by multifunctional asymmetric catalysts as the key step. We previously developed a highly practical catalytic asymmetric Michael reaction using AlLibis(binaphtoxide) (ALB 5). At high concentration (31M) the reaction was highly accelerated and the use of only 0.3mol% of (R)-ALB 5 promoted the Michael reaction of 6 with 7 to completion within 10h, giving Michael adduct 8 in 95% yield and 99% ee. Furthermore, we developed novel highly stable, storable and reusable asymmetric catalyst (R,R)-La-linked-BINOL 10, which also catalyzed this reaction efficiently to give Michael adduct 8 in 94% yield and >99% ee. The catalyst 10 was easily prepared from La(O-i-Pr)_3 and 1.0 equivalent of linked-BINOL 9, which were mixed in THF followed by removal of solvent under reduced pressure to afford 10 as a pale-yellow powder. This air-stable catalyst 10 is storable under air at ambient temperature. After 4 weeks storage, no change in catalytic activity, in terms of both chemical yield and ee, was observed using stock catalyst 10. In addition, the catalyst 10 can be reused several times. After the examination of the scope and limitations of different substrates, we found that the catalyst 10 promoted the Michael reaction of a variety of cyclic enones (n=0-4) with various malonates to afford Michael adducts with good to excellent ee's. The complex 10 was also effective for the Michael reaction of acyclic enones. To the best of our knowledge no efficient catalytic Michael reaction of 8- and 9-membered ring enones with malonates has been reported to date and this is the first example of a Michael reaction where the catalyst shows such broad generality. Having obtained nearly optically pure 8 in large quantities, we next planned to synthesize (-)-strychnine (1) using the Michael adduct 8 as a chiral building block. From the many disconnections, we chose the strategy based on the Stille coupling reaction, intramolecular 1,4-addition reaction of amine to enone, and intramolecular alkylation. This approach requires the precursor α-iodoenone 38, which could be prepared by regioselective enone forming reaction followed by iodination of the corresponding enone. Because the (E)-side chain of 40 would evolve to F and G rings of (-)-strychnine (1), stereoselective introduction of this unit would solve the stereochemical problem posed by the allylic ether double bond at C(20). The synthesis of the (E)-α,β-unsaturated ester 40 was achieved by using a modified Overmann's procedure. In this reaction, we found that the E/Z-selectivity and yield of this reaction are highly dependent on the reaction temperature. At ?55℃ the best result, 70% (2 steps) and E:Z=>15:1, was obtained. In the oxidation step of the corresponding allylic alcohol using MnO_2 the kinetic resolution was observed. (E)-allylic alcohol was oxidized much faster than (Z)-allylic alcohol to afford almost pure (E)-α,β-unsaturated aldehyde 45. After the introduction of C-ring moiety by reductive amination, we next examined the regioselective enone forming reaction. As we expected, more bulky base gave higher selectivity (48:47=up to 6:1). Using these inseparable mixtures, DMAP promoted the iodination of 48 to afford the α-iodoenone 38 with unreacted 47. Using the α-iodoenone 38, we next examined the Stille coupling reaction. At first we could get only trace amount of coupling product 50 even at higher temperature. However, we found that the addition of catalytic amount of CuI dramatically accelerated the coupling reaction even at room temperature to afford the coupling product 50 in quantitative yield. After the exchange of the protecting group of allylic alcohol from PMB to MEM followed by deprotection of Boc, we examined 1,4-addition reaction of amine. After many attempts, we finally found that only BnNMe_3OH is able to promote the reaction effectively to give cyclized compound 36 after deprotection of TBDPS. The primary alcohol of compound 36 was converted to phenyl sulfonate which was cyclized to give the key intermediate 35 subsequently.
  • S Matsunaga, T Ohshima, M Shibasaki
    TETRAHEDRON LETTERS 41 44 8473 - 8478 2000年10月 [査読有り][通常論文]
     
    Polymer-supported linked-BINOL was synthesized to immobilize asymmetric catalysts with two BINOL units. The advantage of the polymer-supported linked-BINOL over randomly polymer-supported BINOL was confirmed by asymmetric Michael reaction. A novel polymer-supported La-Zn-linked-BINOL complex afforded the Michael adduct in good yield and moderate ee. (C) 2000 Elsevier Science Ltd. All rights reserved.
  • YS Kim, S Matsunaga, J Das, A Sekine, T Ohshima, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 122 27 6506 - 6507 2000年07月 [査読有り][通常論文]
  • S Matsunaga, J Das, J Roels, EM Vogl, N Yamamoto, T Iida, K Yamaguchi, M Shibasaki
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 122 10 2252 - 2260 2000年03月 [査読有り][通常論文]
     
    The catalytic enantioselective meso-epoxide ring opening reaction with phenolic oxygen nucleophile (4-methoxyphenol) is described for the first time herein. This reaction was first found to he promoted by (R)-GaLB (Ga = gallium, L = lithium, B = (R)-BINOL), giving a variety of epoxide opening products in good to high ee (67-93% ee). However, chemical yield was only modest (yield 31-75%). despite the use of more than 20 mol % GaLB. This was due to the undesired ligand exchange between BINOL and 4-methoxyphenol, which resulted in the decomplexation of GaLB. Application of various known chiral ligands such as 6,6'-bis((triethylsilyl)ethynyl)-BINOL and H-8-BINOL were examined, but satisfactory results were not obtained. To overcome this problem a novel linked-BINOL containing coordinative oxygen atom in the linker has been developed. By linking two BINOL units in GaLB, the stability of the Ga-complex was greatly improved. Using 3-10 mol % (R,R)-Ga-Li-linked-BINOL complex, a variety of epoxide opening reactions were found to proceed smoothly, affording products in analogous ee (66-96% ee) and in much higher yield (yield 67-94%) compared to (R)-GaLB. The structure of the LiCl free Ga-Li-linked-BINOL complex was elucidated by X-ray analysis. This is the first X-ray data for an asymmetric catalyst containing gallium. The possible mechanism of the entitled reaction is also discussed, based on the X-ray structure of the Ga-complex.
  • EM Vogl, S Matsunaga, M Kanai, T Iida, M Shibasaki
    TETRAHEDRON LETTERS 39 43 7917 - 7920 1998年10月 [査読有り][通常論文]
     
    The synthesis of new C-2-symmetric chiral ligands consisting of two binaphthol units linked by a short bridge is described. These ligands can be used for investigating catalytic asymmetric reactions which utilize BINOL or related ligands as was demonstrated for the ring opening reaction of cyclohexene oxide with 4-methoxyphenol. (C) 1998 Elsevier Science Ltd. All rights reserved.
  • T Iida, N Yamamoto, S Matsunaga, HG Woo, M Shibasaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 37 16 2223 - 2226 1998年08月 [査読有り][通常論文]

講演・口頭発表等

その他活動・業績

受賞

  • 2020年09月 有機合成化学協会 Mukaiyama Award 2020
     
    受賞者: 松永茂樹
  • 2019年01月 北海道大学 北海道大学教育研究総長表彰
     
    受賞者: 松永茂樹
  • 2018年03月 JST, ACT-C 根岸賞
     
    受賞者: 松永茂樹
  • 2016年07月 トムソン・ロイター(Clarivate Analytics) 第4回リサーチフロントアワード
     コバルト触媒によるC-H結合活性化 
    受賞者: 松永茂樹
  • 2011年05月 Merck-Banyu Lectureship Award, MBLA 2010
     
    受賞者: 松永茂樹
  • 2009年03月 三井化学 三井化学触媒化学奨励賞
     
    受賞者: 松永茂樹
  • 2007年03月 日本化学会 日本化学会進歩賞
     
    受賞者: 松永茂樹

共同研究・競争的資金等の研究課題

  • 第9族金属触媒-キラル酸ハイブリッドの精密化による不斉C-H官能基化の深化と拡張
    日本学術振興会:科学研究費助成事業 基盤研究(B)
    研究期間 : 2020年04月 -2023年03月 
    代表者 : 松永 茂樹
  • 新規キラル複核錯体の創製を基盤とする不活性C-H結合の触媒的不斉官能基化法の開拓
    日本学術振興会:科学研究費助成事業 基盤研究(B)
    研究期間 : 2017年04月 -2020年03月 
    代表者 : 松永 茂樹
     
    初年度の検討結果を踏まえ、銅-パラジウムの組み合わせを基盤とする複核シッフ塩基触媒について重点的に検討を進めた。分子内アリル位C-Hアミノ化反応を引き続き触媒評価に利用することとし、基質について、昨年度の末端アルケンを有する基質ではなく、内部アルケンのアリル位C-H活性化が可能かどうかについて評価をおこなった。その結果、ラセミ反応においてもっとも優れた触媒の一つとされるWhite触媒では極めて低い反応性にとどまる内部アルケンのアリル位についても全く問題なく活性化できることがわかった。また、アミノ化反応のエナンチオ選択性について評価したところ、90:10のエナンチオマー比で生成物が得られることがわかった。当初の想定と異なり、ジアミンについてはアキラルなエチレンジアミンが最適であり、キラルスルホキシドのみのキラリティで良好な選択性を得ることが出来た点は興味深い。 一方、ジアミンを変更すると大きく触媒構造が変化することから、金属の組み合わせについても再度、検討を行ったが、やはり銅とパラジウムの組み合わせが最適であった。第一列遷移金属の選択が、エナンチオ選択性に大きく影響している原因を明らかとするべく、種々のシッフ塩基錯体のX線結晶構造解析を行った。その結果、内部に組み込む金属の種類によって、触媒中に2つ存在するキラルスルホキシド部の距離が大きく変化することが判明した。キラルスルホキシドの片方が主として機能している可能性が示唆されたため、最終年度では、構造活性相関を含め詳細な検討を進めたい。
  • 精密多点制御を実現する触媒反応活性点の設計と有用物質変換への応用
    日本学術振興会:科学研究費助成事業 新学術領域研究(研究領域提案型)
    研究期間 : 2015年06月 -2020年03月 
    代表者 : 松永 茂樹
     
    昨年度までに見いだしていたビナフチルスルホン酸を母骨格とするキラルアニオンと高原子価ロジウム触媒とを組み合わせた触媒系を活用することで炭素-水素結合活性化後の官能基化段階における不斉誘導に成功した。反応機構解析の結果、キラルスルホン酸がプロトンを供与する際に立体選択性が発現していることが示唆された。共同研究成果として論文公表を行った。スピロ骨格を母骨格とするキラルスルホン酸を活用することで、基質適用範囲の拡張にも成功し、抗ウイルス作用等が期待される6-アリールプリンのC-H官能基化における不斉誘導にも成功した。スピロキラルスルホン酸は有機触媒としても有効であることもあわせて報告した。 キラルカルボン酸とコバルト触媒を併用することで、従来報告例のなかったsp3炭素-水素結合の活性化における、エナンチオトピックな二つのメチル基C-H結合の識別に成功した。チオアミド基のアミド化に成功した。コバルト触媒においては、比較的単純なアミノ酸由来のキラルカルボン酸が有効である事を見いだしたが、コバルト触媒の配位子であるシクロペンタジエニル基上に一つt-ブチル基を導入することで高い立体選択性の発現につなげられることが判明した。 ロジウム触媒に対して有効なキラルカルボン酸については、引き続き検討の余地はあるものの、ビナフチル骨格を有するキラルカルボン酸を新たに設計することで、たsp3炭素-水素結合の活性化における不斉誘導が中程度の立体選択性で進行する事を見いだした。最終年度にはさらなる改良を実施し、成果の取りまとめを実施する。 キラル二核ルテニウム触媒については、機能探索、触媒構造解析を順番に実施した。触媒的不斉シクロプロパン化、C-Hアミノ化、ヘテロDiels-Alder反応において既存のロジウム触媒を凌駕する触媒活性を有することを明らかとした。
  • キラルアニオン戦略に基づくアジリジンC-H結合の不斉アリル化と天然物合成への応用
    日本学術振興会:科学研究費助成事業 特別研究員奨励費
    研究期間 : 2016年11月 -2019年03月 
    代表者 : 松永 茂樹, LIN LUQING
     
    高原子価のロジウム触媒に対して最適なカルボン酸として、ビナフチル骨格を基盤としジアリールホスフィンオキシド部を導入した最適なものを決定した。最適化されたキラルカルボン酸を利用することで、脂肪族アミンを配向基として利用し、二つの芳香環のエナンチオトッピックな炭素-水素結合のうち片方を選択的に活性化することに成功した。ジアゾマロネートとのC-Hアルキル化反応は効率よく、かつ、高い立体選択性でアルキル化体が得られた。生成物は、反応条件下、ラクタム環を形成しており、脱炭酸反応と組み合わせる事で、高エナンチオ選択的なイソキノロン合成法として有用である。開発した反応の有用性を実証するために、不斉四級炭素中心を有するNMDAアンタゴニストFR115427の触媒的不斉合成をおこなった。
    また、本研究の最終目的である高原子価のコバルト触媒に対して有効なキラルカルボン酸についての探索も行った。当初の想定とか異なり、ロジウム触媒で最適化したキラルカルボン酸は有効ではなかったが、面不斉を有するフェロセニルカルボン酸を新たに設計し検討した結果、カルボン酸オルト位に適度なサイズの芳香環を導入する事で良好な選択性が発現する事を見いだした。キラルカルボン酸と高原子価コバルト触媒を組み合わせたハイブリッド型の触媒を利用することで、チオアミドのβ位の炭素-水素結合の不斉識別が可能となった。二つのメチル基のうち片方を選択的にC-Hアミノ化することで不斉四級炭素を有するβ-アミノカルボニル化合物の効率的な不斉合成法を確立する事に成功した。
  • 文部科学省:科学研究費補助金(挑戦的萌芽研究)
    研究期間 : 2015年 -2016年 
    代表者 : 松永 茂樹
  • 文部科学省:科学研究費補助金(基盤研究(B))
    研究期間 : 2014年 -2016年 
    代表者 : 松永 茂樹
  • 日本学術振興会:科学研究費助成事業 新学術領域研究(研究領域提案型)
    研究期間 : 2013年04月 -2015年03月 
    代表者 : 松永 茂樹
     
    当初の研究計画に沿って、以下の検討を実施した。(1)ヒドリド源を活用した求核的な活性種の発生については、コバルトヒドリド種を活用することで活性な求核種をスチレン誘導体から得る手法を確立していた。26年度にはピンサー型の触媒を活用することで、触媒量の低減化に成功した。(2)また、高原子価のコバルト触媒を活用した反応系については、これまでのイミンへの付加反応に加えて、ホスホラミド化およびベンズアミドの酸化的アルケニル化などへの適用についても検討し、問題無く反応が進行することを確認した。(3)さらに、触媒構造のうち、これまでほとんど検討してこなかったシクロペンタジエン部について、修飾を施した触媒について系統的な検討を進めた。その結果、あまりにも立体障害要因を小さくしてしまった場合には、触媒の安定性が大きく低下し、触媒活性が失われることがわかった。一方で、ごくわずかに立体障害要因を減らすことで、活性が向上し、安定性もキープできることが判明した。これはさらに高い触媒活性、反応回転数を実現するための極めて重要な知見であると考えている。以上のように、過去2年間の検討を通じて、各種金属錯体を設計、開発し、これによる炭素-水素結合の活性化とそこからの求核的な活性種を生み出す手法を開拓することに成功した。特に、種々検討を進めた中で、コバルト錯体を利用した反応系については、独自性が高く、まだまだ応用範囲の広がる余地が大きいものであると評価している。実際、2015年になって、他の研究グループが我々の開拓した触媒系を模倣するようになっており、インパクトのある成果であったことを支持している。
  • 日本学術振興会:科学研究費助成事業 若手研究(A)
    研究期間 : 2011年04月 -2015年03月 
    代表者 : 松永 茂樹, 吉野 達彦, 三ツ沼 治信, 加藤 将太, ル ガン, 鈴木 雄大
     
    希土類金属を利用せずに高い触媒活性を有する不斉触媒を新たに開発することに成功した。新たに開発した不斉触媒を活用することで不斉四置換炭素を有する有用な化合物の合成を実践した。希土類を使用する代わりに、豊富に存在するマグネシウム触媒やマンガン触媒に関して、単核ではなく、複数の金属中心をもつ触媒を設計、合成、応用することで、高い触媒活性を獲得した。これにより従来は合成が困難であった各種窒素元素を含む光学活性ビルディングブロックを効率よく合成する手法を確立した。また、確立した手法を応用し、抗がん作用が期待される、阻害剤リード化合物の設計と周辺化合物のライブラリーを構築した。
  • 日本学術振興会:科学研究費助成事業 新学術領域研究(研究領域提案型)
    研究期間 : 2011年04月 -2013年03月 
    代表者 : 松永 茂樹
     
    我々は原子効率に優れた反応様式にこだわり、求核的な活性種を触媒的に系中で発生させ、単純な「水素原子の移動のみ」で新たなC-C結合を形成する直截的な分子変換プロセスの開発に取り組んでいる。その中で、2年間に渡る本研究において従前より取り組んできた複核シッフ塩基錯体の特徴を活かした各種反応開発、および、新たな求核的活性種の触媒的生成を可能にする系の探索に取り組んできた。本年度は、Rh触媒によるアリル位C-H活性化/異性化/交差アルドール反応、高原子価カチオン性コバルト錯体による求核的aryl-Co種の触媒的生成、低原子価コバルト-ヒドリド触媒による求核的alkyl-Co種の触媒的生成など様々な活性触媒種の創製に成功した。これらはそれぞれ直接的なアルドールプロセス、求電子剤との付加反応、ピリジンの直接修飾反応に適用可能であった。また、ピリジンのベンジル位のC-H官能基化についてもさらなる基質適用範囲の拡大に成功した。また、歪みを有する複核シッフ塩基錯体の反応性の拡張にも取り組み、特に第2族金属とメトキシ基を有する配位子から錯体調製を行うことで、金属と配位子がn:nの比率でオリゴマー化した活性種を生み出せることを見いだした。これを活用することで活性が低く、官能基化を触媒的に実現することが困難であったイソインドリノンのベンジル位C-H結合に関して触媒的な活性化と続くイミンとの不斉付加反応を実現することに成功した。
  • 文部科学省:科学研究費補助金(若手研究(A))
    研究期間 : 2008年 -2010年 
    代表者 : 松永 茂樹
     
    希土類と遷移金属という二つの異なる金属種を同一錯体内に取り込んだ新規触媒系に関する基礎的性質の解明を行い、その特性を活用した様々な新規触媒的不斉反応への応用を行った。触媒的不斉ニトロマンニッヒ型反応、イソシアネートのα-付加反応などの開発に成功し、種々の光学活性含窒素ビルディングブロックの構築法を確立することに成功した。これにより医薬品合成における重要な合成素子を提供することが可能となった。
  • 文部科学省:科学研究費補助金(特定領域研究)
    研究期間 : 2008年 -2009年 
    代表者 : 松永 茂樹
     
    平成20年度の検討において従来型のビナフトールを使用した希土類アート錯体では満足のいく結果を与えなかった反応について、21年度には、その課題克服に向けての検討を行った。ジエノラート生成を鍵とする反応形式の追求においてはアルカリ土類錯体が優れた結果を与えることを見いだした。特にβ,γ不飽和エステルをドナーとするアルドール反応においてバリウム-ビナフトール触媒を活用することで最高99%eeにて生成物を得ることに成功した。詳細なメカニズム解析も行い、その結果、直接的触媒的アルドール反応は非常に速い可逆プロセスであり、アルドール反応に続く異性化プロセスにおいて動的な速度論変換が起こっていることが確認された。これは従来型のアルドール反応とは違う制御機構であり、非常に興味深い成果である。また、別なジエノラート生成を鍵とする反応形式として不飽和γ-ラクタムをドナーとする反応の開発にも取り組んだ。この場合には、当初の想定とは異なり、希土類あるいはアルカリ土類金属錯体では良好な結果を得ることは出来なかった。そこで、より幅広く様々な触媒系について探索を進めた結果、最終的に複核のニッケル触媒をうまく活用することで反応が効果的に進行することを見いだした。特に不飽和γ-ラクタムを用いたニトロオレフィンへのマイケル反応およびイミンへのマンニッヒ型反応において非常に高い立体選択性を実現することができた。特に、マンニッヒ型反応においてはすべての基質において99%eeにて反応が進行することを見いだした。
  • 文部科学省:科学研究費補助金(若手研究(B))
    研究期間 : 2005年 -2006年 
    代表者 : 松永 茂樹
     
    平成17年度に得た予備的結果を基盤にして、マンニッヒ反応、アルドール反応の完成を目指し検討を行った。特に、マンニッヒ型反応は医薬合成への展開も視野にいれた検討を行い、抗がん剤使用時における重篤な副作用である嘔吐の抑制効果が期待されるニューロキノン受容体アンタゴニスト:L-733060の全合成を達成した。平成18年度の最大の目標は平成17年度において確立したラセミの系での新規反応を、不斉化することであった。このためには、使用する金属に関して幅広くスクリーニングの必要があったが、平成17年度に得た予備的知見をもとに、今年度、インジウム、ランタン、リチウムを用いた検討を進めた。その結果、トリアルキルインジウムおよびランタンとリチウムを組み合わせた系を新たに開発することができた。特にランタンとリチウムを組み合わせた系により不斉化に成功した。現在、触媒量の低減化へ向けた最終検討段階にまで研究が進展している。触媒的不斉マイケル反応を目指した検討の中では、これまでに開発してきた連結型のビナフトール不斉配位子では十分な結果が得られず、新たに立体因子にチューニングを加えた新規不斉配位子の創製に成功した。これにより鎖状のカルボン酸誘導体に対するマロン酸エステルの触媒的不斉マイケル反応を達成することができた。さらに、ケトイミンへの反応を目指した展開として、アルドイミンの場合よりもルイス酸性の高い触媒を活用する必要があることを考慮し、電子的、立体的因子の変化を可能とする新しい不斉空間を構築できる系を新たに2つ確立できた。
  • 文部科学省:科学研究費補助金(若手研究(B))
    研究期間 : 2002年 -2004年 
    代表者 : 松永 茂樹
     
    本研究の最終年度にあたる本年度は、経済性と環境調和性にすぐれた反応系構築を目指し検討を重ねた結果以下の成果を得た。亜鉛触媒を活用したアンチ選択的な触媒的不斉マンニッヒ型反応の触媒量の低減化に関しては反応条件の詳細な検討により従来の他のグループの報告よりも500倍優れた触媒回転数を達成した。これは現時点で触媒的不斉マンニッヒ型反応に対して世界最高の回転数を示す触媒である。また、昨年度は芳香族アルドイミンからのアンチ選択的なマンニッヒ型反応のみを開発したが、本年度はさらにイミンの保護基を検討した結果、Boc-イミンを用いることで、シン選択的なマンニッヒ型反応の開発に成功した。さらに医薬合成への応用として、シン選択的な触媒的不斉マンニッヒ型反応を活用して抗腫瘍剤として有効なタキソテアの側鎖部の合成を達成した。またエステル等価体を求核剤とした反応開発にも着手し、新規に考案したN-アシルピロールを用いた反応を検討した。昨年度に用いた亜鉛のほかにインジウム金属がイミン活性化および系中でのエノラート生成に優れた性質を示すことを見い出した。配位子のチューニングに関しては、連結型ビナフトール不斉配位子を基軸としたスクリーニングを徹底して検討した。その結果、柔軟で自由度の高いビフェニル骨格を導入することで反応速度を大幅に向上することに成功した。これは従来の不斉配位子と比較して不斉源を半分にできたばかりでなく、高いエナンチオ選択性を維持したまま反応速度を向上させた点で価値が高い。

教育活動情報

主要な担当授業

  • 生命医薬科学概論
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 生命科学院
    キーワード : (生命医薬科学概論) 有機合成化学,天然物化学,神経,免疫,蛋白質,脂質,遺伝子解析,RNA,バイオイメージング解析,薬剤吸収,薬物送達,痛み,立体構造 (生命融合科学概論/ソフトマター科学概論) 生命融合科学,生命情報分子科学,生命物質科学,細胞機能科学,生命機能制御科学,ソフトマター科学,ソフトマター材料科学,ソフトマター生命分子科学,ソフトマター生体物理学,ソフトマター医科学,SDGs (生命システム科学概論) 細胞増殖,細胞極性,細胞分化,形態形成,遺伝子発現,植物免疫,神経回路,動物行動学,能科学,生殖機構,発生,内分泌,ホルモン,オムニバス,現代生命科学,知的財産
  • 創薬有機合成化学特論
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 生命科学院
    キーワード : 不斉触媒、C-H活性化触媒、生物活性化合物の合成
  • 薬学英語Ⅱ
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
  • 有機合成化学演習Ⅱ
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : 位置選択性,官能基選択性,立体選択性,不斉反応,光学活性体
  • 有機化学Ⅱ
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 薬学部
    キーワード : アルケン,アルキン,幾何異性,求電子付加,反応速度論,熱力学、立体化学、共鳴,共役,非局在化,Diels-Alder反応

大学運営

学内役職歴

  • 2020年10月12日 - 2022年3月31日 教育改革室室員
  • 2020年10月12日 - 2022年3月31日 総長補佐


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