MAEGAWA Tomohiro

Department of Pharmaceutical SciencesProfessor/Manager

Last Updated :2024/11/22

■Researcher basic information

Degree

  • doctor(Pharmacology)(Osaka University)

ORCID ID

0000-0003-1580-1110

Research Keyword

  • 環境調和型反応   複素環   有機合成化学   catalytic reaction   synthetic organic chemistry   

Research Field

  • Life sciences / Pharmaceuticals - chemistry and drug development

■Career

Career

  • 2019/04 - Today  School of Pharmaceutical SciencesLaboratory of Medicinal Chemistry, School of Pharmaceutical SciencesProfessor
  • 2013/04 - 2019/03  Kindai UniversitySchool of Pharmaceutical SciencesAssociate Professor
  • 2009/01 - 2013/03  Osaka UniversityGraduate School of Pharmaceutical SciencesSpecial-Appointed Associate Professor
  • 2007/10 - 2008/12  Gifu Pharmaceutical UniversityLaboratory of Medicinal ChemistryLecturer
  • 2007/04 - 2007/09  Gifu Pharmaceutical UniversityLaboratory of Medicinal ChemistryAssistant Professor
  • 2003/04 - 2007/03  Gifu Pharmaceutical UniversityLaboratory of Medicinal ChemistryAssistant Professor

Educational Background

  •        - 2003  Osaka University  薬学研究科  分子薬科学専攻
  •        - 2003  Osaka University  Graduate School, Division of Pharmaceutical Sciences
  •        - 1998  Nagoya University  School of Engineering  応用化・物質化学科
  •        - 1998  Nagoya University  Faculty of Engineering

■Research activity information

Award

  • 2020/08 Kansai Branch, The Society of Synthetic Organic Chemistry Kansai Branch Award of The Society of Synthetic Organic Chemistry
     Development of novel reactions utilizing elemental properties of phosphorus and sulfur atoms
  • 2009 プロセス化学会 2009JSPC優秀賞
     メチレンアセタールの非常に緩和で高選択的な脱保護法の開発 
    受賞者: 藤岡弘道;瀬波賢人;久保大空;南辻裕;前川智弘
  • 2008 有機合成化学協会 東海支部 平成20年度有機合成化学協会東海支部奨励賞
     白金族系触媒を用いた水素同位体標識化法の応用と芳香環水素化反応の開発 
    受賞者: 前川 智弘

Paper

  • Yuta Fujiki; Hiyono Suzuki; Junya Kikuzawa; Keiji Nishiwaki; Norihito Kawashita; Junpei Matsuoka; Akira Nakamura; Tomohiro Maegawa; Akiko Kuwabara; Masafumi Kobayashi; Kouichi Matsumoto
    Chemistry Letters Oxford University Press (OUP) 53 (6) 0366-7022 2024/06 
    Abstract We wish to report a new synthetic approach for diphenylacetylene in which tetrachloroethylene was reacted with phenylboronic acid in the presence of Pd catalyst, followed by a workup procedure to provide the crude product, which was then allowed to react with n-butyllithium via the halogen lithium exchange of Cl atom and loss of Li and Cl atoms to afford the desired diphenylacetylene in good yield.
  • Junpei Matsuoka; Yuna Yano; Yuuka Hirose; Koushi Mashiba; Nanako Sawada; Akira Nakamura; Tomohiro Maegawa
    The Journal of Organic Chemistry American Chemical Society (ACS) 89 (1) 770 - 777 0022-3263 2023/12
  • Akira Nakamura; Jyunya Morimoto; Maho Taniguchi; Haruka Aoyama; Jiadong He; Tomohiro Maegawa
    Tetrahedron Letters Elsevier BV 126 154656 - 154656 0040-4039 2023/08
  • Tomohiro Maegawa; Akira Nakamura; Tohko Kine; Haruna Uenishi; Yuri Maki; Yasuhito Kase; Mayo Takagi
    Synlett Georg Thieme Verlag KG 34 (11) 1253 - 1258 0936-5214 2023/02 
    Abstract We have developed a regioselective synthesis of 3,4-disubstituted isoxazoles by using a chalcone-rearrangement strategy. The reaction of β-ketoacetals with hydroxylamine hydrochloride and pyridine afforded the corresponding 3,4-disubstituted isoxazoles via isoxazolines or oximes. Depending on the substrate, another disubstituted isomer was also obtained under our optimized conditions, and a reaction mechanism for each transformation is proposed.
  • Akira Nakamura; Fei Rao; Kazuchika Ukiya; Riko Matsunaga; Shin-ichiro Ohira; Tomohiro Maegawa
    Organic & Biomolecular Chemistry Royal Society of Chemistry (RSC) 21 (6) 1134 - 1137 1477-0520 2023 
    Herein we present a simple and efficient method for the synthesis of thioaurones (hemithioindigos) from MOM-protected 2′-mercaptochalcones with NBS and pyridine.
  • Tomohiro Maegawa; Yasuyoshi Miki; Ryohei Oishi; Ayumi Maekawa; Kazutoshi Segi; Hiromi Hamamoto; Akira Nakamura
    Synthesis Georg Thieme Verlag KG 54 (18) 4095 - 4103 0039-7881 2022/09 
    Abstract We investigated the reaction of ketoximes with hypervalent iodine reagents. A combination of PhI(OAc)2 and BF3·Et2O promoted the Beckmann rearrangement of ketoximes, thus yielding the corresponding amides. From a detailed investigation of the reaction, we determined that the Beckmann rearrangement is preceded by acetylation of the hydroxy group of the ketoxime in situ, accelerating the Beckmann rearrangement. We confirmed that the acetylated ketoxime undergoes the Beckmann rearrangement with BF3·Et2O. The reaction of ketoximes with Koser’s reagent [PhI(OH)OTs] in the presence of tetrahydrofuran results in hydrolysis, affording the corresponding ketones in high yields at room temperature.
  • Akira Nakamura; Akira Imamiya; Yuichiro Ikegami; Fei Rao; Harumi Yuguchi; Yasuyoshi Miki; Tomohiro Maegawa
    RSC Advances Royal Society of Chemistry (RSC) 12 (47) 30426 - 30431 2022 
    A method for the highly selective synthesis of two benzofuran isomers, 3-formylbenzofurans and 3-acylbenzofurans, by rearranging and subsequently transforming 2-hydroxychalcones has been developed.
  • Akira Nakamura; Kouhei Yamamoto; Ryo Murakami; Norihito Kawashita; Kouichi Matsumoto; Tomohiro Maegawa
    Synthesis Georg Thieme Verlag KG 53 (20) 3862 - 3868 0039-7881 2021/06 [Refereed]
     
    A method for synthesizing six-membered heterocyclic compounds was developed based on the features of O,P-acetals. Sequential reactions of intramolecular cyclization between the methylene carbon atom of O,P-acetal and its electrophilic functional group (ester or protected carbamate) was followed by Horner-Wadsworth-Emmons (HWE) olefination with various aldehydes. The developed one-pot method yielded isochroman-4-one and benzoxazin-3-one derivatives with an alkylidene moiety.
  • Makoto Sako; Keigo Higashida; Ganesh Tatya Kamble; Kevin Kaut; Ankit Kumar; Yuka Hirose; Da-Yang Zhou; Takeyuki Suzuki; Magnus Rueping; Tomohiro Maegawa; Shinobu Takizawa; Hiroaki Sasai
    Organic Chemistry Frontiers Royal Society of Chemistry (RSC) 8 (17) 4878 - 4885 2021 [Refereed]
     
    The catalytic enantioselective oxidative hetero-coupling of arenols using a chiral vanadium(v) complex has been developed.
  • Tomohiro Maegawa; Kana Yoshikawa; Takanori Tabata; Kazuma Fujimura; Natsumi Kuraoka; Akira Nakamura; Yasuyoshi Miki
    HETEROCYCLES The Japan Institute of Heterocyclic Chemistry 103 (2) 1031 - 1031 0385-5414 2021 [Refereed]
  • Akira Nakamura; Kazuki Mimaki; Ken-ichi Tanigami; Tomohiro Maegawa
    Frontiers in Chemistry Frontiers Media SA 8 Article 187  2020/03 [Refereed]
  • Yuuka Hirose; Mirai Yamazaki; Misa Nogata; Akira Nakamura; Tomohiro Maegawa
    The Journal of Organic Chemistry American Chemical Society (ACS) 84 (11) 7405 - 7410 0022-3263 2019/06
  • Dehydroxymethyl Bromination of Alkoxybenzyl Alcohols by Using a Hypervalent Iodine Reagent and Lithium Bromide
    Shibata, Ayako; Kitamoto, Sara; Fujimura, Kazuma; Hirose, Yuuka; Hamamoto, Hiromi; Nakamura, Akira; Miki, Yasuyoshi; Maegawa, Tomohiro
    Synlett 29 2275 - 2278 2018/08 [Refereed]
  • Constraction of azaisoflavone derivatives by hypervalent iodine reagent-mediated oxidative rearrangement of 2'-nitrochalcone
    Akira Nakamura; Reo Takane; Junki Tanaka; Junya Morimoto; Tomohiro Maegawa
    Heterocycles 97 785 - 792 2018/05 [Refereed]
  • Direct Synthesis of Chalcones from Anilides with Phenyl Vinyl Ketones by Oxidative Coupling through C-H Bond Activation
    Maegawa, Tomohiro; Mizui, Ryota; Urasaki, Miki; Fujimura, Kazuma; Nakamura, Akira; Miki, Yasuyoshi
    ACS Omega 3 5375 - 5381 2018/05 [Refereed]
  • Hypervalent Iodine-Mediated Beckmann Rearrangement of Ketoximes
    Oishi, Ryohei; Segi, Kazutoshi; Hamamoto, Hiromi; Nakamura, Akira; Maegawa, Tomohiro; Miki, Yasuyoshi
    Synlett 29 1465 - 1468 2018/03 [Refereed]
  • Akira Nakamura; Hodaka Kanou; Junki Tanaka; Akira Imamiya; Tomohiro Maegawa; Yasuyoshi Miki
    Organic and Biomolecular Chemistry Royal Society of Chemistry 16 (4) 541 - 544 1477-0520 2018 [Refereed]
     
    A mild oxidation method for the conversion of aldoximes to carboxylic acids was developed mediated by hypervalent iodine reagents. This method covers a wide range of functionalized aldoximes and proceeds under mild conditions, utilizing PhI(OH)OTs as an oxidant.
  • Yasunari Monguchi; Masahiro Mizuno; Tomohiro Ichikawa; Yuki Fujita; Eri Murakami; Tomohiro Hattori; Tomohiro Maegawa; Yoshinari Sawama; Hironao Sajiki
    JOURNAL OF ORGANIC CHEMISTRY AMER CHEMICAL SOC 82 (20) 10939 - 10944 0022-3263 2017/10 [Refereed]
     
    In the presence of palladium on carbon (Pd/C) as a catalyst, hydrogenation of aliphatic nitriles in cyclohexane efficiently proceeded at 25-60 degrees C under ordinary hydrogen gas pressure to afford the corresponding tertiary amines. However, the use of rhodium on carbon (Rh/C) led to the highly selective generation of secondary amines. Hydrogenation of aromatic nitriles and cyclohexanecarbonitrile selectively produced secondary amines in the presence of either Pd/C or Rh/C.
  • Reiya Ohta; Yuichi Kuboki; Yuki Yoshikawa; Yasuyuki Koutani; Tomohiro Maegawa; Hiromichi Fujioka
    JOURNAL OF FLUORINE CHEMISTRY ELSEVIER SCIENCE SA 201 1 - 6 0022-1139 2017/09 [Refereed]
     
    A versatile and chemoselective route has been developed for the synthesis of aliphatic fluorinated methyl ethers (ROCH2RF), specifically monofluoromethyl ethers (ROCH2F) and trifluoromethylthiomethyl ethers (ROCH2SCF3), through pyridinium-type salt intermediates derived from methoxymethyl (MOM) ethers. The addition of a fluorine source (F- or SCF3-) to the pyridinium-type salts afforded the corresponding fluorinated methyl ethers in good yields under mild conditions. Notably, the synthesis of monofluoromethyl ethers proceeded within just 5 min.
  • Akira Nakamura; Satoshi Tanaka; Akira Imamiya; Reo Takane; Chiaki Ohta; Kazuma Fujimura; Tomohiro Maegawa; Yasuyoshi Miki
    ORGANIC & BIOMOLECULAR CHEMISTRY ROYAL SOC CHEMISTRY 15 (32) 6702 - 6705 1477-0520 2017/08 [Refereed]
     
    An efficient one-pot method was developed for the construction of 3-acylindoles via oxidative rearrangement of 2-aminochalcones followed by intramolecular cyclization. The reaction was used to convert a variety of 2-aminochalcones into 3-acylindoles in moderate to high yields.
  • Tomohiro Maegawa; Misa Nogata; Yuuka Hirose; Shun Ohgami; Akira Nakamura; Yasuyoshi Miki; Hiromichi Fujioka
    Journal of Organic Chemistry American Chemical Society 82 (14) 7608 - 7613 1520-6904 2017/07 [Refereed]
     
    A novel transformation reaction of methylene acetals, using a combination of trimethyl(phenylthio)silane (PhSTMS) and N-bromosuccinimide (NBS) under mild reaction conditions, is described. Various methylene acetals were converted to their corresponding bromoformates in good to high yields. Under the given conditions, the reaction proceeded via a radical pathway. Further transformation of bromoformates to their corresponding epoxides was achieved by treatment with NaOMe.
  • Yasuyoshi Miki; Yukari Hirata; Noriko Makino; Yuuka Hirose; Misa Nogata; Akira Nakamura; Hiromi Hamamoto; Tomohiro Maegawa
    HETEROCYCLES PERGAMON-ELSEVIER SCIENCE LTD 94 (7) 1269 - 1279 0385-5414 2017/07 [Refereed]
     
    We studied selective bromination and iodination of dimethyl indole-2,3-dicarboxylates using phenyliodine diacetate (PIDA), LiBr, and LiI in the presence of Lewis acid. The protective group on the nitrogen of indole is important for selectivity of the halogenation position, and the use of a benzenesulfonyl group as a protective group resulted in preferential halogenation of indole at the 6-position.
  • Tomohiro Maegawa; Misa Nogata; Takaya Honda; Akira Nakamura; Yasuyoshi Miki
    HETEROCYCLES PERGAMON-ELSEVIER SCIENCE LTD 95 (1) 608 - 614 0385-5414 2017/01 [Refereed][Invited]
     
    A novel approach to producing the quinoline skeleton from 2-aminochalcone was developed. Treatment of benzyloxycarbonyl (Cbz)-protected 2-aminochalcones with BF3 center dot Et2O afforded quinoline derivatives via the deprotection of the Cbz group and isomerization of olefin in a one-pot reaction. The reaction of various 2-aminochalcones proceeded to give the corresponding 2-arylquinoline derivatives in good yields. This method is applicable to the rapid synthesis of dubamine.
  • Hiromi Hamamoto; Hideaki Umemoto; Misako Umemoto; Chiaki Ohta; Emi Fujita; Akira Nakamura; Tomohiro Maegawa; Yasuyoshi Miki
    HETEROCYCLES PERGAMON-ELSEVIER SCIENCE LTD 91 (3) 561 - 572 0385-5414 2015/03 [Refereed]
     
    Hypervalent iodine mediated decarboxylative halogenation of indoledicarboxylic acid derivatives was studied. The treatment of 1-methylindole-2,3-dicarboxylic acid with phenyliodine diacetate (PIDA) in the presence of lithium bromide gave 1-methyl-3,3-bromooxindole. However, the reaction of 1-(phenylsulfonyl)indole-2,3-dicarboxylic acid with PIDA in the presence of lithium bromide afforded 2,3-dibromo-1-(phenylsulfonyl)indole. In a similar manner, the 2,3-dichloro- and 2,3-diiodoindole derivatives could be obtained by the reaction of the indole-2,3-dicarboxylic acids with PIDA in the presence of lithium chloride and iodide. This method was optimized to the synthesis of polybromoindole alkaloids.
  • Hideaki Umemoto; Takuya Onaka; Yasuyoshi Miki; Akira Nakamura; Tomohiro Maegawa
    SYNLETT GEORG THIEME VERLAG KG 26 (2) 205 - 208 0936-5214 2015/01 [Refereed]
     
    The reaction of 2-[ (trimethylsilyl) methyl]-2H-tetrazoles with various alkyl halides and carbonates using n-butyllithium or lithium diisopropylamide (LDA) gave 2-[1-(trimethylsilyl) alkyl]-2H-tetrazoles and (2H-tetrazol-2-yl) acetates as useful synthons of modified tetrazoles.
  • Hideaki Umemoto; Takuya Onaka; Yasuyoshi Miki; Akira Nakamura; Tomohiro Maegawa
    HETEROCYCLES PERGAMON-ELSEVIER SCIENCE LTD 89 (11) 2545 - 2553 0385-5414 2014/11 [Refereed]
     
    2-((Trimethylsilyl)methyl)-2H-tetrazoles were treated with aldehydes and ketones in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give 2-(2-hydroxyethyl)-2H-tetrazoles. This simple procedure offers a valuable strategy for the preparation of 2-(hydroxyethyl)-2H-tetrazoles.
  • Takuya Onaka; Hideaki Umemoto; Yasuyoshi Miki; Akira Nakamura; Tomohiro Maegawa
    JOURNAL OF ORGANIC CHEMISTRY AMER CHEMICAL SOC 79 (14) 6703 - 6707 0022-3263 2014/07 [Refereed]
     
    A mild and regioselective 2-arylation of 5-substituted tetrazoles is described. The reaction proceeds regioselectively with a variety of arylboronic acids in the presence of [Cu(OH)(TMEDA)](2)Cl-2 to afford 2,5-disubstituted tetrazoles. This is the first report of highly regioselective arylation of 5-alkyltetrazoles.
  • Yoshiaki Kitamura; Kazumi Taniguchi; Tomohiro Maegawa; Yasunari Monguchi; Yukio Kitade; Hironao Sajiki
    HETEROCYCLES PERGAMON-ELSEVIER SCIENCE LTD 88 (1) 233 - 243 0385-5414 2014/01 [Refereed]
     
    We have developed an environmentally friendly and highly efficient solvent-free Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction using a polymer-supported copper catalyst (Cu/HP20). Substrates poorly soluble in common organic solvents are also applicable to the present cycloaddition reaction without any solvents and provide the corresponding 1,4-triazole in high yields.
  • Tomohiro Maegawa; Hiromichi Fujioka
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN SOC SYNTHETIC ORGANIC CHEM JPN 71 (7) 694 - 705 0037-9980 2013/07 [Refereed]
     
    Although acetals are useful protective groups for carbonyl functions and widely used in organic synthesis, their protection and deprotection under acidic conditions unable to use the substrates with acid labile functions. We recently found that the combination of TESOTf (Et3Si0Tf) 2,6lutidine or 2,4,6-collidine was effective for the deprotection of acetal. The reaction proceeded under nearly neutral conditions and was applicable to the substrates with acid labile functions, and the most noteworthy of this method is the achievement of the chemoselective deprotection of acetals in the presence of ketals. The above reaction proceeds via pyridinium-type salt intermediates, which are found to be highly reactive toward various nucleophiles not only H20 but also heteroatom and carbon nucleophiles affording the corresponding substituted products. This reaction could be conducted under mild reaction conditions whereas conventional methods need harsh reaction conditions. This methodology is also applicable to the deprotection of acetal-type protective groups such as MOM-type ethers, THP ether, and methylene acetal, and the combination of TMSOTf (TESOTf) 2,2'-bipyridyl afforded the best result
  • Tomohiro Maegawa; Yasuyuki Koutani; Kazuki Otake; Hiromichi Fujioka
    Journal of Organic Chemistry 78 (7) 3384 - 3390 0022-3263 2013/04 [Refereed]
     
    A mild and efficient method for formation of methylene acetals from 1,2- and 1,3-diols using methoxymethylphenylsulfide, 1,3-dibromo-5,5- dimethylhydantoin (DBDMH), and dibutylhydroxytoluene (BHT) is described. The use of BHT in this process suppresses side reactions and enables high-yielding formation of methylene acetals of various diols, including carbohydrate-type substrates. © 2013 American Chemical Society.
  • 荒井 孝義; 前川 智弘; 藤岡 弘道; 佐藤 敏文; 山本 靖典
    有機合成化学協会誌 The Society of Synthetic Organic Chemistry, Japan 71 (7) 731 - 731 0037-9980 2013
  • Takahashi Tohru; Yoshimura Masatoshi; Suzuka Hiroyasu; Maegawa Tomohiro; Sawama Yoshinari; Monguchi Yasunari; Sajiki Hironao
    TETRAHEDRON 68 (39) 8293 - 8299 0040-4020 2012/09 [Refereed]
  • Akihiro Goto; Kazuki Otake; Ozora Kubo; Yoshinari Sawama; Tomohiro Maegawa; Hiromichi Fujioka
    CHEMISTRY-A EUROPEAN JOURNAL WILEY-V C H VERLAG GMBH 18 (36) 11423 - 11432 0947-6539 2012/09 [Refereed]
     
    The effects of phosphorus substituents on the reactivity of alpha-alkoxyphosphonium salts with nucleophiles has been explored. Reactions of a-alkoxyphosphonium salts, prepared from various acetals and tri(o-tolyl)-phosphine, with a variety of nucleophiles proceeded efficiently. These processes represent the first examples of high-yielding nucleophilic substitution reactions of a-alkoxyphosphonium salts. The reactivity of these salts was determined by a balance between steric and electronic factors, respectively, represented by cone angles theta and CO stretching frequencies nu (steric and electronic parameters, respectively). In addition, a novel reaction of a-alkoxyphosphonium salts derived from Ph3P with Grignard reagents was observed to take place in the presence of O-2 to afford alcohols in good yields. A radical mechanism is proposed for this process that has gained support from isotope-labeling and radical-inhibition experiments.
  • Tomohiro Maegawa; Kazuki Otake; Keiichi Hirosawa; Akihiro Goto; Hiromichi Fujioka
    ORGANIC LETTERS AMER CHEMICAL SOC 14 (18) 4798 - 4801 1523-7060 2012/09 [Refereed]
     
    Highly substituted four- and five-membered heterocycles were prepared starting with O,P- and N,P-acetals by using a one-pot method involving base induced cyclization and a Horner-Wadsworth-Emmons (HWE) olefination reaction. Divergent synthesis of various heterocycles was achieved by using this method and transformations of the alkenyl group in the products of these processes were exemplified. Finally, a short and efficient synthesis of (+/-)-pseudodeflectusin based on the new methodology was achieved.
  • Yutaka Minamitsuji; Atsuhisa Kawaguchi; Ozora Kubo; Yoshifumi Ueyama; Tomohiro Maegawa; Hiromichi Fujioka
    ADVANCED SYNTHESIS & CATALYSIS WILEY-V C H VERLAG GMBH 354 (10) 1861 - 1866 1615-4150 2012/07 [Refereed]
     
    A mild and divergent route for the synthesis of alkyl ethers from methoxymethyl (MOM) and methoxyethyl (ME) ether derivatives via pyridinium-type salt intermediates has been developed. The addition of organocuprates to the salts afforded the corresponding alkyl ethers, including highly crowded ones, in high yields even in the presence of acid- or base-sensitive functional groups.
  • Sawama Yoshinari; Yabe Yuki; Shigetsura Masahiro; Yamada Tsuyoshi; Nagata Saori; Fujiwara Yuta; Maegawa Tomohiro; Monguchi Yasunari; Sajiki Hironao
    ADVANCED SYNTHESIS & CATALYSIS Wiley 354 (5) 777 - 782 1615-4150 2012/03 [Refereed]
  • Hiromichi Fujioka; Kenzo Yahata; Tomohito Hamada; Ozora Kubo; Takashi Okitsu; Yoshinari Sawama; Takuya Ohnaka; Tomohiro Maegawa; Yasuyuki Kita
    CHEMISTRY-AN ASIAN JOURNAL WILEY-V C H VERLAG GMBH 7 (2) 367 - 373 1861-4728 2012/02 [Refereed]
     
    Mild substitution reactions of acetals with carbon nucleophiles via the pyridinium-type salts generated by the treatment of acetals with TESOTf-2,4,6-collidine or 2,2'-bipyridyl have been developed. Various carbon nucleophiles, such as organocuprates, silyl enol ethers, enamines, etc., reacted with the pyridinium-type salts to give the corresponding substituted products in good yields. The reactions proceeded under very mild conditions (non-acidic conditions) and thus acid-sensitive functional groups can be tolerated during the reaction. In addition, only an acetal can form the pyridinium-type salt and react with nucleophiles in the presence of a ketal. This unusual selectivity is in contrast to general methods conducted under acidic conditions.
  • Nkaelang Modutlwa; Hiroyuki Tada; Yoshiki Sugahara; Koichi Shiraki; Nobuyuki Hara; Yoshihiro Deyashiki; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    HETEROCYCLES PERGAMON-ELSEVIER SCIENCE LTD 84 (1) 419 - 429 0385-5414 2012/01 [Refereed]
     
    N-6-Benzyladenine (benzyladenine), a plant growth regulator, was efficiently deuterated by the hydrogen deuterium (H D) exchange reaction catalyzed by palladium on carbon-ethylenediamine complex [Pd/C(en)], while use of palladium on carbon (Pd/C) as a catalyst led to a low deuterium incorporation at room temperature or complete removal of the N-6-benzyl group at 110 degrees C or higher temperature. The obtained benzyladenine-d(5) was used as an internal standard (surrogate) for the quantification of residual benzyladenine in fruits, vegetables, cereals, and beans using LC/MS/MS. Satisfactory recovery of benzyladenine between 94.2 and 105.7% (100.4% on the average) was obtained. The agrochemical could be detected within the concentration range of 0.25-0.50 ng/g in agricultural products using the present quantification method.
  • Maegawa T; Koutani Y; Senami K; Yahata K; Fujioka H
    Heterocycles 86 (1) 455 - 467 2012 [Refereed]
  • Takashi Ikawa; Yuki Fujita; Tomoteru Mizusaki; Sae Betsuin; Haruki Takamatsu; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    ORGANIC & BIOMOLECULAR CHEMISTRY ROYAL SOC CHEMISTRY 10 (2) 293 - 304 1477-0520 2012 [Refereed]
     
    Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH4OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction.
  • Amos B. Smith; Shuzhi Dong; Richard J. Fox; Jehrod B. Brenneman; John A. Vanecko; Tomohiro Maegawa
    TETRAHEDRON PERGAMON-ELSEVIER SCIENCE LTD 67 (51) 9809 - 9828 0040-4020 2011/12 [Refereed]
     
    An effective, asymmetric total synthesis of the antibiotic (+)-sorangicin A (1) has been achieved. Central to this venture was the development of first- and second-generation syntheses of the signature dioxabicyclo[3.2.1]octane core, the first featuring chemo- and stereoselective epoxide ring openings facilitated by a Co-2(Co)(6)-alkyne complex, the second involving a KHMDS-promoted epoxide ring formation/opening cascade. Additional highlights include effective construction of the dihydro- and tetrahydropyran ring systems, respectively, via a stereoselective conjugate addition/alpha-oxygenation protocol and a thioketalization/hydrostannane reduction sequence. Late-stage achievements entailed two Julia-Kocienski olefinations to unite three advanced fragments with high E-stereoselectivity, followed by a modified Stille protocol to introduce the Z,Z,E trienoate moiety, thereby completing the carbon skeleton. Mukaiyama macrolactonization, followed by carefully orchestrated Lewis and protic acid-promoted deprotections that suppressed isomerization and/or destruction of the sensitive (Z,Z,E)-trienoate linkage completed the first, and to date only, total synthesis of (+)-sorangicin A (1). (C) 2011 Elsevier Ltd. All rights reserved.
  • Yasunari Monguchi; Yuki Fujita; Shota Hashimoto; Mariko Ina; Tohru Takahashi; Ryo Ito; Kei Nozaki; Tomohiro Maegawa; Hironao Sajiki
    TETRAHEDRON PERGAMON-ELSEVIER SCIENCE LTD 67 (45) 8628 - 8634 0040-4020 2011/11 [Refereed]
     
    The solvent-free and solid-phase hydrogenation of various reducible functionalities was efficiently catalyzed by heterogeneous palladium on carbon (Pd/C) under ambient hydrogen pressure and temperature. The Pd/C-catalyzed Suzuki-Miyaura coupling reaction between solid aryl bromides and solid arylboronic acids to generate the corresponding solid biaryls was also achieved under the totally solid-phase conditions. (C) 2011 Elsevier Ltd. All rights reserved.
  • Yuta Fujiwara; Youhei Iwasaki; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    CHEMCATCHEM WILEY-BLACKWELL 3 (10) 1624 - 1628 1867-3880 2011/10 [Refereed]
     
    An efficient and practical procedure for the hydrogenation of aliphatic and aromatic ketones under mild reaction conditions is established. The method is highly effective even for the hydrogenation of sterically hindered ketones. Furthermore, the selective hydrogenation of the carbonyl group of aromatic ketones was achieved with the aromatic nuclei and the resulting secondary benzyl alcohol moiety still intact on addition of catalytic amount of pyridine.
  • Tomohiro Maegawa; Kazuki Otake; Akihiro Goto; Hiromichi Fujioka
    ORGANIC & BIOMOLECULAR CHEMISTRY ROYAL SOC CHEMISTRY 9 (16) 5648 - 5651 1477-0520 2011 [Refereed]
     
    A new direct conversion of O,O-acetals to esters via O,P-acetal intermediates was developed. The regioselective cleavage of unsymmetrical cyclic acetals occurred to give the more crowded esters as single isomers.
  • Ozora Kubo; Kenzo Yahata; Tomohiro Maegawa; Hiromichi Fujioka
    CHEMICAL COMMUNICATIONS ROYAL SOC CHEMISTRY 47 (32) 9197 - 9199 1359-7345 2011 [Refereed]
     
    A diastereoselective ring contraction of the diastereomixture of 2,4-disubstituted 1,3-dioxepins to 2,5-cis-2,3,5-trisubstituted tetrahydrofurans was achieved using TfOH in DMF. The reaction appears to proceed via a chair-like transition state, in which stereomutation of the oxocarbenium occurred, followed by an aldol-type cyclization.
  • Hiromichi Fujioka; Akihiro Goto; Kazuki Otake; Ozora Kubo; Yoshinari Sawama; Tomohiro Maegawa
    CHEMICAL COMMUNICATIONS ROYAL SOC CHEMISTRY 47 (35) 9894 - 9896 1359-7345 2011 [Refereed]
     
    An unusual and novel reaction of alpha-alkoxyphosphonium salts, generated from O,O-acetals and Ph3P, with Grignard reagents under an O-2 atmosphere afforded alcohols in moderate to high yields. It was clarified by isotopic labelling experiments that the reaction proceeded via a novel radical pathway.
  • Hiromichi Fujioka; Kenzo Yahata; Ozora Kubo; Yoshinari Sawama; Tomohito Hamada; Tomohiro Maegawa
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION WILEY-V C H VERLAG GMBH 50 (51) 12232 - 12235 1433-7851 2011 [Refereed]
  • Tohru Takahashi; Yusuke Iida; Yuta Fujiwara; Yuya Inagaki; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY AMER CHEMICAL SOC 239 0065-7727 2010/03
  • Hetero-Suzuki-Miyaura Cross-Coupling Using Palladium on Carbon
    Kitamura Yoshiaki; Sako Satoko; Tsutsui Azusa; Monguchi Yasunari; Maegawa Tomohiro; Kitade Yukio; Sajiki Hironao
    Synfacts GEORG THIEME VERLAG KG 7 844 - 844 2010
  • LC-MS/MSを用いたクロバザムとその代謝物であるN-デスメチルクロバザムの高速及び高感度なハイスループット分析
    谷口 和美; 中村 光浩; 大森 智史; 門口 泰也; 前川 智弘; 井口 和弘; 伊藤 善規; 臼井 茂之; 佐治木 弘尚; 平野 和行
    日本薬学会年会要旨集 (公社)日本薬学会 129年会 (4) 100 - 100 0918-9823 2009/03
  • Akiko Ido; Shinji Ishihara; Ryota Kobayashi; Akira Kume; Tomohiro Maegawa; Yasunari Monguchi; Sueo Wada; Hironao Sajiki; Hisamitsu Nagase
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY AMER CHEMICAL SOC 237 0065-7727 2009/03 [Refereed]
  • Yasunari Monguchi; Akira Kume; Shinji Ishihara; Sueo Wada; Tomohiro Maegawa; Hisamitsu Nagase; Hironao Sajiki
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY AMER CHEMICAL SOC 237 0065-7727 2009/03 [Refereed]
  • Shinji Ishihara; Akiko Ido; Tomohiro Maegawa; Yasunari Monguchi; Sueo Wada; Hisamitsu Nagase; Hironao Sajiki
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY AMER CHEMICAL SOC 237 0065-7727 2009/03 [Refereed]
  • Nkaelang Modutlwa; Hiroyuki Tada; Yoshiki Sugahara; Koichi Shiraki; Nobuyuki Hara; Yoshihiro Deyashiki; Takayuki Ando; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    Nucleic acids symposium series (2004) (53) 105 - 106 2009 [Refereed]
     
    Palladium on carbon-ethylenediamine complex [Pd/C(en)] catalyzed deuteration of N(6)-benzyladenine-d(5), which is a plant growth regulator, to introduce 5 deuterium atoms, while use of Pd/C as a catalyst led to a complete removal of N(6)-benzyl group. The corresponding deuterated N(6)-benzyladenine was successfully used as a surrogate compound for the quantitative analysis of residual benzyladenine in crops using LC/MS/MS.
  • Akinori Mori; Tomoteru Mizusaki; Masami Kawase; Tomohiro Maegawa; Yasunari Monguchi; Shinobu Takao; Yukio Takagi; Hironao Sajiki
    ADVANCED SYNTHESIS & CATALYSIS WILEY-BLACKWELL 350 (3) 406 - 410 1615-4150 2008/02 [Refereed]
     
    A diphenyl sulfide immobilized on palladium-on-carbon system, Pd/C[Ph(2)S], was developed to achieve the highly chemoselective hydrogenation of alkenes, acetylenes, azides, and nitro groups in the presence of aromatic ketones, halides, benzyl esters, and N-Cbz protective groups. Instrumental analyses of the heterogeneous catalyst demonstrated that diphenyl sulfide was embedded on Pd/C via coordination of its sulfur atom to palladium metal or physical interaction with graphite layers of the activated carbon. The catalyst could be recovered and reused at least five times without any significant loss of the reactivity.
  • Nobuhiro Ito; Hiroyoshi Esaki; Tsuneaki Maesawa; Eikoh Imamiya; Tomohiro Maegawa; Hironao Sajiki
    BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN CHEMICAL SOC JAPAN 81 (2) 278 - 286 0009-2673 2008/02 [Refereed]
     
    An effective and applicable deuteration method for aromatic rings using Pt/C-D2O-H-2 system was established. Especially, phenol was fully deuterated even at room temperature, and other electron-rich aromatic nuclei were efficiently deuterated under mild conditions. The scope and limitations of the presence method and its application to the synthesis of deuterium-labeled biologically active compounds and deuterium-labeled building blocks for practical multi-gram scale syntheses are reported.
  • Monguchi Yasunari(Gifu; Pharmaceutical University; Kitamura Yoshiaki(Gifu University; Maegawa Tomohiro(Gifu; Pharmaceutical University; Sajiki Hironao(Gifu; Pharmaceutical University
    ケミカルエンジニアリング 化学工業社 53 (4) 256 - 261 0387-1037 2008
  • Mori S; Yanase T; Aoyagi S; Monguchi Y; Maegawa T; Sajiki H
    Chemistry (Weinheim an der Bergstrasse, Germany) 14 (23) 6994 - 6999 0947-6539 2008 [Refereed]
     
    A variety of aryl iodides were coupled with aromatic and aliphatic terminal alkynes to give the corresponding 1,2-disubstituted aromatic alkynes in good yields by using only 0.4 mol % of the heterogeneous 10 % Pd/C as the catalyst without a ligand, copper salt, or amine in an aqueous medium.
  • Yoshiaki Kitamura; Satoko Sako; Takahiro Udzu; Azusa Tsutsui; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    Chemical Communications ROYAL SOC CHEMISTRY 5069 - 5071 1359-7345 2007/12 [Refereed]
     
    We have developed a mild and efficient protocol for the ligand-free and heterogeneous Pd/C-catalyzed hetero Suzuki-Miyaura coupling reaction that allows for the synthesis of both heteroaryl-aryl and heteroaryl-heteroaryl derivatives in good to excellent yields. © The Royal Society of Chemistry.
  • Takanori Kurita; Masami Abe; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    SYNLETT GEORG THIEME VERLAG KG (16) 2521 - 2524 0936-5214 2007/10 [Refereed]
     
    A facile and environmentally friendly synthetic method for a variety of symmetrical 1,3-diyne derivatives based on the Pd/C-Cul-catalyzed homocoupling reaction of terminal alkynes has been developed. The reaction was efficiently catalyzed by the extrernely low loading (0.01-0.03 mol%) of Pd/C and Cul (3 mol%) in the presence of molecular oxygen (02) as an oxidant without any phosphine ligands and bases.
  • Yoshiaki Kitamura; Ai Sakurai; Takahiro Udzu; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    Tetrahedron PERGAMON-ELSEVIER SCIENCE LTD 63 (43) 10596 - 10602 0040-4020 2007/10 [Refereed]
     
    Heterogeneous Pd/C-catalyzed Suzuki-Miyaura cross-coupling reaction of aryl boronic esters with aryl bromides was successfully carried out in aqueous media at room temperature without the use of a ligand such as phosphine derivatives. © 2007 Elsevier Ltd. All rights reserved.
  • Tomohiro Maegawa; Yoshiaki Kitamura; Satoko Sako; Takahiro Udzu; Ai Sakurai; Asami Tanaka; Yusuke Kobayashi; Koichi Endo; Utpal Bora; Takanori Kurita; Atsushi Kozaki; Yasunari Monguchi; Hironao Sajiki
    Chemistry - A European Journal WILEY-V C H VERLAG GMBH 13 (20) 5937 - 5943 0947-6539 2007/08 [Refereed]
     
    A mild and efficient ligand-free Suzuki-Miyaura coupling reaction catalyzed by heterogeneous Pd/C was developed. Aryl bromides and triflates undergo the cross-coupling with aryl boronic acids in excellent yields without the presence of any additives in aqueous media at room temperature. Aryl vinyl boronic acids are also applicable to this coupling reaction and provide the trans-stilbene derivatives in high yields. The application of wet-type Pd/C to the coupling reaction was achieved without any loss of activity under aerobic conditions, and the reuse of Pd/C is feasible for a fifth run without significant loss of activity. Inductively coupled plasma (ICP) mass-spectrometric analysis of the filtrate from the reaction mixture of 4-bromonitrobenzene with phenylboronic acid demonstrated that the palladium metal hardly leached into the solution within the limits of the detector (< 1 ppm), thus suggesting that the present Suzuki-Miyaura reaction proceeded by heterogeneous catalysis. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.
  • Tomohiro Maegawa; Yuki Fujita; Ai Sakurai; Akira Akashi; Mutsumi Sato; Keiji Oono; Hironao Sajiki
    CHEMICAL & PHARMACEUTICAL BULLETIN PHARMACEUTICAL SOC JAPAN 55 (5) 837 - 839 0009-2363 2007/05 [Refereed]
     
    Aromatic nitriles are not only important components of natural products, pharmaceuticals, herbicides and agrochemicals but also a synthetic equivalent of various functionalities. The development of synthetic methods of aromatic nitriles have been increasing in terms of its usefulness. Since aromatic nitriles are susceptible to the hydrogenation, it has been desired for the development of chemoselective hydrogenation method with retention of nitrile groups. Pd/C is one of the most popular catalysts for hydrogenation and many of reducible functional groups such as multiple bonds, benzyl ethers, N-Cbzs, nitro groups and so on could be easily reduced under the conditions. Therefore, it is very difficult to achieve the chemoselective hydrogenation of substrates containing two or more reducible functional groups. We have found that a Pd/C catalyst formed an isolable complex with ethylenediamine (en) employed as catalytic poison, and the complex [Pd/C(en)] catalyzed chemoselective hydrogenation of a variety of reducible functionalities distinguishing O-benzyl, N-Cbz and O-TBDMS protective groups, benzyl alcohols and epoxides. In the course of these investigations, we found the aryl nitriles could survive under the Pd/C(en)-catalyzed hydrogenation conditions in THF whose choice is important for the effective suppression. This methodology could be applied to the selective hydrogenation of alkene and alkyne functionalities in the presence of aromatic nitrile.
  • Hiroyoshi Esaki; Rumi Ohtaki; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    JOURNAL OF ORGANIC CHEMISTRY AMER CHEMICAL SOC 72 (6) 2143 - 2150 0022-3263 2007/03 [Refereed]
     
    A liquid-phase redox system between secondary alcohols and ketones is described. Deuteration of either secondary alcohols or ketones using the Pd/C-H-2-D2O system gave a mixture of deuterium-labeled secondary alcohols and ketones. The results indicated that the secondary alcohol was oxidized to the corresponding ketone without oxidants under the hydrogenation conditions and the hydrogenation of the aliphatic ketone to the corresponding secondary alcohol simultaneously proceeded. Detailed mechanistic studies on the redox system as well as the H-D exchange reaction are discussed.
  • Akinori Mori; Tomoteru Mizusaki; Takashi Ikawa; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    TETRAHEDRON PERGAMON-ELSEVIER SCIENCE LTD 63 (5) 1270 - 1280 0040-4020 2007/01 [Refereed]
     
    We have found that phenolic hydroxyl groups were readily deoxygenated via aryl sulfonate under the Pd/C-catalyzed hydrogenation conditions in the presence of diethylamine and the method could also be applicable to the hydrodeoxygenation of morphine to afford 3-deoxy-7,8-dihydromorphine. Diethylamine is not only a scavenger of the corresponding methanesulfonic acid derivative, which is produced during the reaction progress, but also a strong promoter of the Pd/C-catalyzed reduction of aryl sulfonates. This catalyst system could provide a general method for the deoxygenation of various phenol derivatives because of its mild reaction conditions, ease of handling, and no need of particular apparatus. (c) 2006 Elsevier Ltd. All rights reserved.
  • Akinori Mori; Tomoteru Mizusaki; Takashi Ikawa; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    CHEMISTRY-A EUROPEAN JOURNAL WILEY-V C H VERLAG GMBH 13 (5) 1432 - 1441 0947-6539 2007 [Refereed]
     
    A method for the deoxygenation of phenolic hydroxy groups via aryl triflates or mesylates has been established by using a combination of Pd/C-Mg-MeOH. The addition of NH4OAc to the system markedly accelerated the reaction rate and expanded the scope of the reaction. Mechanistic studies suggested that a single-electron transfer process from the Pd-0 center to the benzene ring is involved in the reduction of aryl sulfonates and that NH4OAc works as a solubilization reagent of the Mg salt and as an accelerator of the electron transfer, thus enhancing the reaction process. Our method was also applicable to the regioselective deuteration of benzene derivatives with CH3OD as the solvent and deuterium source: the original hydroxy group could be efficiently replaced with a deuterium atom.
  • Yoshiaki Kitamura; Asami Tanaka; Mutsumi Sato; Keiji Oono; Takashi Ikawa; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    Synthetic Communications 37 (22) 4381 - 4388 0039-7911 2007/01 [Refereed]
     
    A practical and efficient preparation method of palladium-fibroin (Pd/Fib),
    silk-fibroin-supported Pd(0) by means of sonication, has been developed. The Pd/Fib
    catalyst could be prepared within 12 h at room temperature starting from commercial
    silk-fibroin and Pd(OAc)2 in MeOH, whereas our previous preparation method required
    at least 4 days. The present improved process is applicable to a large-scale preparation
    of Pd/Fib. The Pd/Fib prepared by the present method also catalyzed chemoselective
    hydrogenation of acetylenes, olefins, and azides in the presence of aromatic ketones,
    aldehydes, and halides; N-Cbz protective groups; and benzyl esters, which are
    readily hydrogenated under the Pd/C- or Pd/C(en)-catalyzed hydrogenation
    conditions. @ 2007 Taylor & Francis Group, LLC.
  • Akinori Mori; Tornoteru Mizusaki; Yurni Miyakawa; Eri Ohashi; Tornoko Haga; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    TETRAHEDRON PERGAMON-ELSEVIER SCIENCE LTD 62 (51) 11925 - 11932 0040-4020 2006/12 [Refereed]
     
    While Pd/C is one of the most useful catalysts for hydrogenation, the high catalyst activity of Pd/C causes difficulty in its application to chemoselective hydrogenation between different types of reducible functionalities. In order to achieve chemoselective hydrogenation using Pd/C, we investigated catalyst poison as a controller of the catalyst activity. We found that the addition of Ph2S (diphenylsulfide) to the Pd/C-catalyzed hydrogenation reaction mixture led to reasonable deactivation of Pd/C. By the use of the Pd/C-Ph2S catalytic system, olefins, acetylenes, and azides can be selectively reduced in the coexistence of aromatic carbonyls, aromatic halides, cyano groups, benzyl esters, and N-Cbz (benzyloxycarbonyl) protecting groups. The present method is promising as a general and practical chemoselective hydrogenation process in synthetic organic chemistry. (c) 2006 Elsevier Ltd. All rights reserved.
  • Hiroyoshi Esaki; Nobuhiro Ito; Shino Sakai; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    TETRAHEDRON PERGAMON-ELSEVIER SCIENCE LTD 62 (47) 10954 - 10961 0040-4020 2006/11 [Refereed]
     
    A protocol of a versatile H-D exchange reaction of heterocyclic compounds catalyzed by heterogeneous Pd/C in D2O is described. The reaction of various nitrogen-containing heterocycles with 10% Pd/C (10 wt % of the substrate) under hydrogen atmosphere in D2O as a deuterium source at 110-180 degrees C for 24 h afforded the corresponding deuterated compounds with satisfactory efficiency of deuteration in moderate to excellent isolated yields. Furthermore, the Pd/C-H-2-D2O system can be extended to the direct deuteration of biologically active compounds such as sulfamethazine, which is used as a synthetic antibacterial drug for fat stocks and would be applied as a general method for the preparation of the standard materials for the analysis of residual chemicals in foods and so on. (c) 2006 Elsevier Ltd. All rights reserved.
  • Yasunari Monguchi; Akira Kume; Kazuyuki Hattori; Tomohiro Maegawa; Hironao Sajiki
    TETRAHEDRON PERGAMON-ELSEVIER SCIENCE LTD 62 (33) 7926 - 7933 0040-4020 2006/08 [Refereed]
     
    A mild and efficient one-pot procedure for the hydrodechlorination of aromatic chlorides using a Pd/C-Et3N system was developed. A variety of aromatic chlorides could be dechlorinated at room temperature and under ambient hydrogen pressure. Et3N activates the catalysis and is likely to work as a single electron donor in this system. (c) 2006 Elsevier Ltd. All rights reserved.
  • Akinori Mori; Yumi Miyakawa; Eri Ohashi; Tomoko Haga; Tomohiro Maegawa; Hironao Sajiki
    ORGANIC LETTERS AMER CHEMICAL SOC 8 (15) 3279 - 3281 1523-7060 2006/07 [Refereed]
     
    A Pd/C-catalyzed chemoselective hydrogenation using diphenylsulfide as a catalyst poison has been developed. This methodology selectively hydrogenates olefin and acetylene functionalities without hydrogenolysis of aromatic carbonyls and halogens, benzyl esters, and N-Cbz protective groups.
  • Nobuhiro Ito; Tsutomu Watahiki; Tsuneaki Maesawa; Tomohiro Maegawa; Hironao Sajiki
    ADVANCED SYNTHESIS & CATALYSIS WILEY-V C H VERLAG GMBH 348 (9) 1025 - 1028 1615-4150 2006/06 [Refereed]
     
    We have found a synergistic effect in the H-D exchange reaction of alkyl-substituted aromatic compounds using the Pd/C-Pt/C-D2O-H-2 system. This system would lead to fully H-D exchange results even on the sterically hindered sites which were only low-deuterium incorporated by Pd/C or Pt/C independently. Since the reaction was general for a variety of aromatic compounds, it could be applied to the deuteration of dianiline derivatives as raw materials for polyimides.
  • Tomohiro Maegawa; Akira Akashi; Hironao Sajiki
    SYNLETT GEORG THIEME VERLAG KG (9) 1440 - 1442 0936-5214 2006/06 [Refereed]
     
    A mild and complete hydrogenation of aromatic rings catalyzed by heterogeneous 10% Rh/C proceeds at 80 degrees C in water under 5 atm of H-2 pressure. This method is applicable to the hydrogenation of various carbon and heteroaromatic compounds such as alkylbenzenes, biphenyls, pyridines and furans.
  • H Sajiki; A Mori; T Mizusaki; T Ikawa; T Maegawa; K Hirota
    ORGANIC LETTERS AMER CHEMICAL SOC 8 (5) 987 - 990 1523-7060 2006/03 [Refereed]
     
    A Pd/C-catalyzed deoxygenation method of phenolic hydroxyl groups via aryl triflates or mesylates using Mg metal in MeOH at room temperature was developed. The addition of NH4OAc dramatically affects the reactivity and reaction rate. This method is particularly attractive to provide an environmentally benign and widely applicable removal method of phenolic alcohols under quite mild reaction conditions.
  • H Esaki; F Aoki; T Maegawa; K Hirota; H Sajiki
    HETEROCYCLES PERGAMON-ELSEVIER SCIENCE LTD 66 361 - 369 0385-5414 2005/12 [Refereed]
     
    The D-2 gas-free and base-selective H-D exchange reaction of nucleosides was developed. It discloses a convenient route to the post-synthetic incorporation of deuteriums into the base moiety of nucleic acids with high deuterium efficiency.
  • Maegawa T; Hirota K; Tatematsu K; Mori Y; Sajiki H
    The Journal of organic chemistry 70 (25) 10581 - 10583 0022-3263 2005/12 [Refereed]
  • H Sajiki; N Ito; H Esaki; T Maesawa; T Maegawa; K Hirota
    TETRAHEDRON LETTERS PERGAMON-ELSEVIER SCIENCE LTD 46 (41) 6995 - 6998 0040-4039 2005/10 [Refereed]
     
    An effective and applicable Pt/C-catalyzed deuteration method of aromatic rings using D2O as a deuterium source under hydrogen atmosphere was developed. Five percent Pt/C would lead to quite effective H-D exchange results on the aromatic ring systems. The reaction is general for a variety of aromatic compounds including biologically active compounds. (c) 2005 Elsevier Ltd. All rights reserved.
  • Hironao Sajiki; Takanori Kurita; Atsushi Kozaki; Guolin Zhang; Guolin Zhang; Yoshiaki Kitamura; Tomohiro Maegawa; Kosaku Hirota
    Journal of Chemical Research 344  0308-2342 2005/05

MISC

Books and other publications

Affiliated academic society

  • ヨウ素学会   日本プロセス化学会   有機合成化学協会   アメリカ化学会   日本薬学会   The Society of Synthetic Organic Chemistry, Japan   The Pharmaceutical Society of Japan   

Research Themes

  • 日本学術振興会:科学研究費助成事業
    Date (from‐to) : 2023/04 -2027/03 
    Author : 前川 智弘
  • Development and application of novel reactions exploiting the potential activation ability of sulfur atoms towards halogen compounds.
    Kobayashi Foundation:小林財団 研究助成
    Date (from‐to) : 2024/04 -2027/03
  • 硫黄化合物を用いる高活性なハロゲン化反応の開発とその応用
    文部科学省:科学研究費補助金(基盤研究(C))
    Date (from‐to) : 2018/04 -2022/03 
    Author : 前川 智弘
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014 -2016 
    Author : MAEGAWA Tomohiro
     
    We developed a novel transformation reaction of methylene acetal using Phenylthiotrimethylsilane and N-bromosuccinimide. The reaction proceeded under mild conditions to afford the corresponding bromoformates, which could be converted to the corresponding epoxides by the treatment of NaOMe. This reaction was applicable to one-pot transformation from methylene acetal to eppoxide. The methylene acetal derived from aminoalcohol was also transformed under the same conditions giving the corresponding product.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2012 -2013 
    Author : MAEGAWA Tomohiro
     
    Heterocyclic compounds are utilized in pharmaceuticals, agrochemicals and functional materials. Recently, oxygen-containing 4-membered heterocycles, oxetane, has been reported as a useful skeleton to improve a pharmaceutical quality. We developed a facile oxetane synthesis using O,P-acetal consisted of phosphorous and oxygen as a key intermediate. The feature of this method is eco-conscious double use of phosphorous atom in one reaction. We also succeeded in synthesizing natural product having anticancer activity in short steps using our method.
  • ホスホニウム塩中間体を利用する有機合成化学:新規基盤反応の開発と天然物合成への応用
    武田科学振興財団:薬学系研究奨励
    Date (from‐to) : 2011 -2013 
    Author : 前川 智弘
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2006 -2007 
    Author : SAJIKI Hironao; MAEGAWA Tomohiro; MONGUCHI Yasunari
     
    The Pd/C-catalyzed H_2-D_2 exchange reaction between D_2O and H_2 and its application to the preparation of deuterium labeled compounds have been demonstrated. H_2 sealed in the reaction flask was efficiently converted into pure D_2, which can be used for the one-pot reductive deuteration of a variety of reducible functionalities. Furthermore, the chemoselective deuterogenation of olefins and acetylenes was accomplished by the addition of a trace amount of Ph_2S with retention of the various other reducible functionalities. A method of capturing the generated D_2 gas was also developed. The significant features of the H_2-D_2 exchange reaction are efficiency, inexpensiveness, environmental-friendly and convenience. Furthermore, a simple, mild, and regioselective H-D exchange reaction at the benzylic sites using the heterogeneous Pd/C as a catalyst without expensive D_2 gas was developed. The present method can afford the corresponding deuterium-labelled compounds with excellent deuterium efficiency. The use of 10% Pd/C in the presence of a small amount of hydrogen gas could achieve an efficient H-D exchange using the less expensive D-2O as the deuterium source at room temperature for 72 h. Furthermore, this reaction is dramatically accelerated under mild heating (50℃) conditions, resulting in shortening the reaction time and expanding the applicability of the substrates. The H-D exchange reaction could also be used for the deuteration of benzyl ethers, which were generally unstable under Pd/C-catalyzed hydrogenation conditions, with a high deuterium efficiency using Pd/C(en) instead of Pd/C. Furthermore, the use of THE and D_2O mixed (7:3) solvent successfully suppressed the hydrogenolysis of the corresponding benzyl ether. The present method would also be very useful for the simplification of complex ^1H NMR charts. The general utility of these methodologies will make such simple techniques an attractive addition to the wide range of deuteration procedures.
  • 文部科学省:科学研究費補助金(若手研究(B))
    Date (from‐to) : 2005 -2006 
    Author : 前川 智弘
     
    タンパク質や酵素等の高次構造解析や反応機構の解明等に用いられる重水素(D)標識化合物は小分子量のD標識シントンやH-D交換反応等により合成されるが、いずれの手法も手間がかかる、高価な試薬・特殊な反応条件を必要とするなどの問題点を有している。一方、当研究室ではこれまでにPd/C-D_2O-H_2の組み合わせによる簡便重水素化法の開発に成功し、一般性ある高効率的D標識体合成法として確立している。また、Pt/C存在下では芳香環上でのD化反応が優先的に進行することを見出し、さらにPd/C及びPt/C共存下では芳香環及びアルキル炭素上でのD化反応が同時に進行し1段階での多重D化反応が進行することを見出している。そこでより効率的なD化法並びにD化触媒の開発を目的として異なる触媒反応点を有するPdとPtを活性炭に同時に担持させた複合金属触媒の調製及び反応性の検討を行った。まず触媒を調製するにあたり、触媒の調製法による反応性の違いについて検討した。一般にPdの活性炭担持型触媒の調製法としては2価のPd金属の溶液中に活性炭を加えた後、還元剤で0価に還元する方法により調製する。そこで今回、より高活性な複合触媒の調製を目的として、還元剤に水素、ヒドラジン、ホルムアルデヒド、水素化ホウ素ナトリウムの4種を用いて触媒を調製したところ、水素化ホウ素ナトリウムを還元剤に用いて調製した触媒が最も高い活性を示し、芳香環、アルキル側鎖共に高効率的にD化を受けることが明らかとなった。また、本触媒はD化反応において相乗効果が発現することが明らかとなり、Pd/CまたはPt/Cを単独で用いた場合よりも高い重水素化率で反応が進行し、特に立体的に込み合った部位での重水素化が効率的に進行することを明らかとした。
  • Efficient and facile C-H/C-D exchange reaction of organic compounds using heterogeneous Pd/C.
    Date (from‐to) : 2003 -2006
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
    Date (from‐to) : 2004 -2005 
    Author : HIROTA Kosaku; SAJIKI Hironao; MAEGAWA Tomohiro
     
    Recently, we found that 9-benzyl-8-hydroxyadenine (1)possesses relatively potent interferon (IFN)-inducing activity as a lead compound. Further effort to establish the structure-activity relationship reached 2-butoxy- 9-bennzyl- 8-hydroxyandenine (2)as the most active compounds, whose potencies were 10^4-fold greater than that of the lead compound (1). In this research synthesis of higher active analog and fluorescent ligand for Toll-like receptor 7 (TLR-7), whose agonist is such 8-hydroxyandenies, were investigated and the following results were obtained. 1)Chemical modification of the 2-position of adenines : Introduction of various substituents into the 2-position were attempted. 2-MeO(CH_2)_2O- and 2-MeOCH_2S- analogs indicated similar activity to compound 2. 2)Synthesis of 1- or 3- deazaadenine derivatives : The oral bioavailability of compound 2 is remarkably low. Synthesis of 1- or 3-deaza analogs, which are expected increase of lipophilicity, was planed to improve the oral absorption of compound 2. Synthesis of 9-benzyl-2-butoxy-3-deazaadenine (3) and 9-Benzyl-2-butoxy-1-deazaadenine (4) were establiched using 4-amino-2,6-dichloropyridine as a starting compound. Now introduction of an 8-hydroxy group into the deazaadenines (3 and 4) is carried out. 3)Synthesis of fluorescent ligand for Toll-like receptor 7 (TLR-7) : 8-Hydroxyadenine (2) is a strong agonist of TLR-7 and mutual interaction causes production of a large amount of IFN. Synthesis of 8-hydroxyadenine derivative possessing a fluorescent functional group instead of benzyl group at the 9-position was investigated as a probe for analysis of the structure and function of TLR-7. Introduction of anthranylmethyl group resulted in failure in performance caused by low solubility. Various synthetic approaches are now under investigation.
  • 日本学術振興会:科学研究費助成事業
    Date (from‐to) : 2001 -2002 
    Author : 前川 智弘
     
    今回、申請者らは、水中での無機塩KBrの添加による低反応性、低溶解性の超原子価ヨウ素試薬PhIOの新規活性化法を利用したアルコール類の酸化反応の更なる展開を目的として研究を行った。まず、前年度、我々が見出したジオール類の酸化反応の拡張として異種分子間での酸化的エステル化反応を検討した。その結果、第1級アルコールの酸化反応の際にメタノールを共存させることで種々の第1級アルコール類から対応するメチルエステル体を収率良く得ることに成功した。今回、我々が見出した方法は一般性も高く、無水条件や過剰量の試薬を必要とした従来法に比べ、含水条件で行える簡便かつ収率の良いメチルエステル化反応である。さらに回収、再利用が可能なポリマー担持型超原子価ヨウ素試薬poly(diactoxyiodo)styrene(PDAIS)の利用を検討した結果、水中でのアルコール類の酸化反応と同様、本反応においても首尾良く反応が進行し、試薬のリサイクルも問題なく行えることが分かった。また、本活性化法を用いても困難であった電子吸引基を有する低活性なビアリールスルフィド類の酸化反応においてPhIOに比べ、より活性なphenyliodine diacetate (PIDA)を用いることでスルホンをほとんど副生することなく対応するスルホキシド類を収率良く与えることを見出した。また、PDAISを用いても首尾良く反応が進行し、種々のスルフィド類から対応するスルホキシド類を高収率で得ることに成功した。

Others

  • 2015/04 -2015/04  Transition metal catalyzed chalcone synthesis using direct coupling reaction 
    We developed a novel chalcone synthesis using direct coupling reaction of vinyl ketone and aromatic ring without any halogen atom.