研究者データベース

研究者情報

マスター

アカウント(マスター)

  • 氏名

    久保田 浩司(クボタ コウジ), クボタ コウジ

所属(マスター)

  • 工学研究院 応用化学部門 有機工業化学分野

所属(マスター)

  • 工学研究院 応用化学部門 有機工業化学分野

researchmap

プロフィール情報

所属

  • 北海道大学, 大学院工学研究院, 准教授
  • 北海道大学化学反応創成研究拠点 (WPI-ICReDD)

学位

  • 工学博士(2016年03月 北海道大学)

プロフィール情報

  • 公開用メールアドレス

    kbteng.hokudai.ac.jp
  • 久保田
  • 浩司, クボタコウジ
  • ID各種

    201801013729902406

所属

  • 北海道大学, 大学院工学研究院, 准教授
  • 北海道大学化学反応創成研究拠点 (WPI-ICReDD)

業績リスト

研究キーワード

  • メカノケミストリー   触媒的不斉合成   有機触媒   有機合成化学   有機金属化学   

研究分野

  • ナノテク・材料 / 有機合成化学
  • ライフサイエンス / 生物有機化学
  • ナノテク・材料 / 構造有機化学、物理有機化学

経歴

  • 2021年04月 北海道大学大学院工学研究院 准教授
  • 2019年04月 - 2020年03月 北海道大学化学反応創成研究拠点 特任助教
  • 2018年04月 - 2019年03月 北海道大学大学院工学研究院 特任助教
  • 2017年04月 - 2018年03月 マサチューセッツ工科大学 日本学術振興会海外特別研究員 (Stephen L. Buchwald研究室)
  • 2016年06月 - 2017年03月 カリフォルニア大学バークレー校 博士研究員 (F. Dean Toste研究室)
  • 2016年04月 - 2016年06月 北海道大学大学院工学研究院 日本学術振興会博士研究員 (伊藤肇研究室)

学歴

  • 2013年10月 - 2016年03月   北海道大学   総合化学院   博士 (伊藤肇研究室)
  • 2012年04月 - 2013年09月   北海道大学   総合化学院   修士 (伊藤肇研究室)
  • 2008年04月 - 2012年03月   北海道大学   工学部   応用理工系学科応用化学コース

委員歴

  • 2021年04月 - 現在   北海道大学大学院工学研究院   国際連携委員会
  • 2021年04月 - 現在   北海道大学化学反応創成研究拠点 (WPI-ICReDD)   新棟機器運営委員会
  • 2020年04月 - 現在   北海道大学化学反応創成研究拠点 (WPI-ICReDD)   セミナー運営委員会
  • 2019年10月 - 2021年10月   公益財団法人 MSD生命科学財団   大津会議 ファシリテーター
  • 2021年04月 - 2021年07月   北海道大学化学反応創成研究拠点 (WPI-ICReDD)   第二回サイトビジット対策委員会

受賞

  • 2019年09月 2019 ACP Lectureship Award from Singapore
     
    受賞者: 久保田 浩司
  • 2019年07月 47th Naito Conference on C-H Bond Activation and Transformation Best Poster Award
     
    受賞者: 久保田 浩司
  • 2018年 第34回 井上研究奨励賞
     
    受賞者: 久保田 浩司
  • 2017年 Lindau Nobel Laureate Meeting Fellow
     
    受賞者: 久保田 浩司
  • 2016年 2016 Springer Thesis Award
     
    受賞者: 久保田 浩司
  • 2016年 Reaxys PhD Prize 2016 Finalist
     
    受賞者: 久保田 浩司
  • 2015年 2015 Pacifichem Student Competition Poster Award
     
    受賞者: 久保田 浩司
  • 2015年 第6回大津会議研究企画賞
     
    受賞者: 久保田 浩司
  • 2015年 第6回大津会議アワードフェロー
     
    受賞者: 久保田 浩司
  • 2015年 第7回HOPE Meeting Best Presentation Award
     
    受賞者: 久保田 浩司
  • 2015年 第7回HOPE Meeting Fellow
     
    受賞者: 久保田 浩司
  • 2014年 北海道大学大塚博先生記念賞
     
    受賞者: 久保田 浩司
  • 2012年 第59回有機金属化学討論会ポスター賞
     
    受賞者: 久保田 浩司
  • 2012年 北海道大学William Wheeler Prize (応用化学コース首席卒業)
     
    受賞者: 久保田 浩司

論文

  • Takumi Takeuchi, Ryosuke Shishido, Koji Kubota, Hajime Ito
    Chemical Science 2021年08月 [査読有り]
     

    The synthesis of a series of hydrosilylboronates via the selective iridium- or nickel-catalyzed monoborylation of dihydrosilane Si−H bonds is described. The synthesized silylboronates, which bear a single Si−H bond, can...

  • Koji Kubota, Daiyo Miura, Takumi Takeuchi, Shun Osaki, Hajime Ito
    ACS Catalysis 11 11 6733 - 6740 2021年06月04日
  • Koji Kubota, Naoki Toyoshima, Daiyo Miura, Julong Jiang, Satoshi Maeda, Mingoo Jin, Hajime Ito
    Angewandte Chemie International Edition 2021年05月14日 [査読有り]
  • Sota Akiyama, Natsuki Oyama, Tsubura Endo, Koji Kubota, Hajime Ito
    Journal of the American Chemical Society 143 13 5260 - 5268 2021年04月07日 [査読有り]
     
    The first catalytic intermolecular 1,2-alkylborylation reaction via a radical-relay mechanism between unactivated olefins, bis(pinacolato)diboron, and an alkyl electrophile is reported. Successful implementation of this method requires that the competing boryl substitution of the alkyl electrophile is retarded to facilitate the radical relay. This challenge was overcome using electronically or sterically demanding alkyl electrophiles, which results in the simultaneous and highly regioselective introduction of a gem-difluoro, monofluoro, tertiary, or secondary alkyl group and a boryl group across the C═C double bond.
  • Tamae Seo, Naoki Toyoshima, Koji Kubota, Hajime Ito
    Journal of the American Chemical Society 2021年03月30日 [査読有り]
     
    Conventional organic synthesis generally relies on the use of liquid organic solvents to dissolve the reactants. Therefore, reactions of sparingly soluble or insoluble substrates are challenging and often ineffective. The development of a solvent-independent solid-state approach that overcomes this longstanding solubility issue would provide innovative synthetic solutions and access to new areas of chemical space. Here, we report extremely fast and highly efficient solid-state palladium-catalyzed Suzuki-Miyaura cross-coupling reactions via a high-temperature ball-milling technique. This solid-state protocol enables the highly efficient cross-couplings of insoluble aryl halides with large polyaromatic structures that are barely reactive under conventional solution-based conditions. Notably, we discovered a new luminescent organic material with a strong red emission. This material was prepared via the solid-state coupling of Pigment violet 23, a compound that has so far not been involved in molecular transformations due to its extremely low solubility. This study thus provides a practical method for accessing unexplored areas of chemical space through molecular transformations of insoluble organic compounds that cannot be carried out by any other approach.
  • Koji Kubota, Hajime Ito
    TRENDS IN CHEMISTRY 2 12 1066 - 1081 2020年12月 [査読有り]
     
    In recent years, solvent-less mechanochemical organic transformations using ball milling have come to the forefront of organic synthesis as cleaner and sustainable synthetic alternatives. Apart from the environmental benefits, mechanochemical approaches potentially enable access to novel chemical space that has reactivities and selectivities different from those of conventional solution-based reactions. In this review, we highlight important recent contributions to cross coupling chemistry using ball milling, with particular emphasis on new synthetic strategies and concepts based on mechanochemical reaction environments that enable the rapid and selective construction of complex molecules.
  • Yadong Pang, Joo Won Lee, Koji Kubota, Hajime Ito
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 59 50 22570 - 22576 2020年12月 [査読有り][通常論文]
     
    The application of piezoelectricity for the generation of trifluoromethyl (CF3) radicals is reported together with the development of a method for the mechanochemical C-H trifluoromethylation of aromatic compounds. As compared to conventional solution-based approaches, this mechanoredox C-H trifluoromethylation enables cleaner and more sustainable access to a wide range of trifluoromethylated N-heterocycles and peptides, which are important structural motifs in modern drug discovery. This study thus represents an important milestone for future applications of mechanoredox systems to medicinal and pharmaceutical science.
  • Koji Kubota, Rikuro Takahashi, Minami Uesugi, Hajime Ito
    ACS SUSTAINABLE CHEMISTRY & ENGINEERING 8 44 16577 - 16582 2020年11月 [査読有り]
     
    Carbon-nitrogen (C-N) bond-forming cross-coupling reactions catalyzed by palladium-based catalysts, the so-called Buchwald-Hartwig aminations, have been widely employed for the synthesis of pharmaceuticals and aryl-amine-based organic materials in academic and industrial settings. However, in solution, these reactions usually require glovebox and Schlenk line techniques, which greatly reduces their practical utility. Here, we report the development of operationally simple mechanochemical C-N cross-coupling reactions in the solid-state. Intensive investigations of various ball milling parameters revealed that the air-stable ligand tri(1-adamantyl)phosphine can be used to achieve solid-state coupling reactions between aryl halides and diarylamines with high efficiency. Notably, all experimental operations of the developed protocol can be carried out in air, thus providing a more convenient, industrially attractive, and sustainable alternative to conventional solution-based palladium-catalyzed C-N coupling reactions.
  • Ryosuke Shishido, Minami Uesugi, Rikuro Takahashi, Tsuyoshi Mita, Tatsuo Ishiyama, Koji Kubota, Hajime Ito
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 142 33 14125 - 14133 2020年08月 [査読有り][通常論文]
     
    Compared to carbon-based nucleophiles, the number of silicon-based nucleophiles that is currently available remains limited, which significantly hampers the structural diversity of synthetically accessible silicon-based molecules. Given the high synthetic utility and ease of handling of carbon-based boron nucleophiles, silicon-based boron nucleophiles, i.e., silylboranes, have attracted considerable interest in recent years as nucleophilic silylation reagents that are activated by transition-metal catalysts or bases. However, the range of practically accessible silylboranes remains limited. In particular, the preparation of sterically hindered and functionalized silylboranes remains a significant challenge. Here, we report the use of rhodium and platinum catalysts for the direct borylation of hydrosilanes with bis(pinacolato)diboron, which allows the synthesis of new trialkylsilylboranes that bear bulky alkyl groups and functional groups as well as new dialkylarylsilylboranes that are difficult to synthesize via conventional methods using alkali metals. We further demonstrate that these compounds can be used as silicon nucleophiles in organic transformations, which significantly expands the scope of synthetically accessible organosilicon compounds compared to previously reported methods. Thus, the present study can be expected to inspire the development of efficient methods for novel silicon-containing bioactive molecules and organic materials with desirable properties. We also report the first B-11{H-1} and Si-29(H-1) NMR spectroscopic evidence for the formation of i-Pr3SiLi generated by the reaction of i-Pr3Si-B(pin) with MeLi.
  • Tamae Seo, Koji Kubota, Hajime Ito
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 142 22 9884 - 9889 2020年06月 [査読有り][通常論文]
     
    Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of liquid, unbiased dibromoarenes under mechanochemical conditions selectively afford the monoarylated products. The lower reactivity of the crystalline monoarylated products relative to the liquid starting materials should be attributed predominantly to the low diffusion efficiency of the former in the reaction mixture, which results in a selective monoarylation. The present study sheds light on a novel approach using in situ phase transitions in solids to design selective organic transformations that are difficult to achieve via conventional solution-based synthesis.
  • Sota Akiyama, Syogo Nomura, Koji Kubota, Hajime Ito
    The Journal of Organic Chemistry 85 6 4172 - 4181 2020年03月20日 [査読有り][通常論文]
  • Hajime Ito, Keiichi Hayama, Ryoto Kojima, Koji Kubota, Hajime Ito
    Organic Letters 2020年01月17日 [査読有り][通常論文]
  • Rina Takahashi, Koji Kubota, Hajime Ito
    CHEMICAL COMMUNICATIONS 56 3 407 - 410 2020年01月 [査読有り][通常論文]
     
    Although xantphos has been employed in a variety of palladium-catalyzed cross-coupling reactions, there has been little progress in developing Xantphos-ligated precatalysts. In this report, we describe a Xantphos-ligated palladium dialkyl complex that acts as a powerful precatalyst for C-N, C-S, and C-C cross-coupling reactions. This precatalyst is air- and moisture stable but can be thermally activated in the absence of external reagents. Additionally, potential catalyst inhibitors are not generated during the precatalyst activation. This complex thus represents a convenient alternative to previously reported classes of Xantphos-ligated precatalysts.
  • Koji Kubota, Yadong Pang, Akira Miura, Hajime Ito
    SCIENCE 366 6472 1500 - + 2019年12月 [査読有り][通常論文]
     
    Over the past decade, photoredox catalysis has harnessed light energy to accelerate bond-forming reactions. We postulated that a complementary method for the redox-activation of small organic molecules in response to applied mechanical energy could be developed through the piezoelectric effect. Here, we report that agitation of piezoelectric materials via ball milling reduces aryl diazonium salts. This mechanoredox system can be applied to arylation and borylation reactions under mechanochemical conditions.
  • Tamae Seo, Tatsuo Ishiyama, Koji Kubota, Hajime Ito
    Chemical Science 10 35 8202 - 8210 Royal Society of Chemistry ({RSC}) 2019年09月 [査読有り][通常論文]
     
    The Suzuki-Miyaura cross-coupling reaction is one of the most reliable methods for the construction of carbon-carbon bonds in solution. However, examples for the corresponding solid-state cross-coupling reactions remain scarce. Herein, we report the first broadly applicable mechanochemical protocol for a solid-state palladium-catalyzed organoboron cross-coupling reaction using an olefin additive. Compared to previous studies, the newly developed protocol shows a substantially broadened substrate scope. Our mechanistic data suggest that olefin additives might act as dispersants for the palladium-based catalyst to suppress higher aggregation of the nanoparticles, and also as stabilizer for the active monomeric Pd(0) species, thus facilitating these challenging solid-state C-C bond forming cross-coupling reactions.
  • Hajime Ito, Sota Akiyama, Koji Kubota, Malte S. Mikus, Paulo H. S. Paioti, Filippo Romiti, Qinghe Liu, Yuebiao Zhou, Amir H. Hoveyda, Hajime Ito
    Angewandte Chemie International Edition 58 35 11998 - 12003 2019年08月26日 [査読有り][通常論文]
  • Hajime Ito, Hiroaki Iwamoto, Kohei Endo, Yu Ozawa, Yuta Watanabe, Koji Kubota, Tsuneo Imamoto, Hajime Ito
    Angewandte Chemie International Edition 58 32 11112 - 11117 2019年08月05日 [査読有り][通常論文]
  • Koji Kubota, Tamae Seo, Katsumasa Koide, Yasuchika Hasegawa, Hajime Ito
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 258 2019年08月 [査読有り]
  • Koji Kubota, Minami Uesugi, Shun Osaki, Hajime Ito
    ORGANIC & BIOMOLECULAR CHEMISTRY 17 23 5680 - 5683 2019年06月 [査読有り][通常論文]
     
    A new method was developed for synthesizing 2-alkyl-2-boryl-tetrahydrofuran derivatives from aliphatic ketones using a copper(i)/N-heterocyclic carbene complex catalyst. This reaction presumably proceeds through the nucleophilic addition of a borylcopper(i) intermediate to ketone, followed by intramolecular substitution of the resulting alkoxide for the halide leaving group. The new borylation products, 2-alkyl-2-boryl-tetrahydrofuran derivatives with a condensed structure around the C-B bond, cannot be synthesized by other methods.
  • Koji Kubota, Rina Takahashi, Hajime Ito
    CHEMICAL SCIENCE 10 22 5837 - 5842 2019年06月 [査読有り][通常論文]
     
    Organic reactions that employ moisture- and/or oxygen-sensitive reagents or intermediates usually involve the use of glove-box or Schlenk-line techniques as well as dry and degassed solvents. Unfortunately, these requirements may greatly reduce the utility of the targeted organic molecules. Herein, we demonstrate that solvent-free mechanochemical synthetic techniques allow using highly oxygen-sensitive palladium(0) species in air for the stoichiometric oxidative addition of aryl halides. The low diffusion efficiency of gaseous oxygen in crystalline or amorphous solid-state reaction mixtures should be the main reason for the low impact of the presence of atmospheric oxygen on the sensitive oxidative addition reactions under the applied conditions. This study thus illustrates the outstanding potential of mechanochemistry to serve as an operationally simple, glove-box-and-Schlenk-line-free synthetic route to organometallic compounds and other valuable synthetic targets, even when sensitive reagents or intermediates are involved.
  • Yadong Pang, Tatsuo Ishiyama, Koji Kubota, Hajime Ito
    Chemistry – A European Journal 25 18 4654 - 4659 Wiley 2019年03月 [査読有り][通常論文]
     
    Mechanochemistry has been applied for the first time to an iridium(I)-catalyzed C-H borylation reaction. By using either none or just a catalytic amount of a liquid, the mechanochemical C-H borylation of a series of heteroaromatic compounds proceeded in air to afford the corresponding arylboronates in good-to-excellent yields. A one-pot mechanochemical C-H borylation/Suzuki-Miyaura cross-coupling sequence for the direct synthesis of 2-aryl indole derivatives is also described. The present study constitutes an important milestone towards the development of industrially attractive solvent-free C-H bond functionalization processes in air.
  • Koji Kubota, Tamae Seo, Katsumasa Koide, Yasuchika Hasegawa, Hajime Ito
    Nature Communications 10 1 2019年01月 [査読有り][通常論文]
     
    Palladium-catalyzed cross-coupling reactions are one of the most powerful and versatile methods to synthesize a wide range of complex functionalized molecules. However, the development of solid-state cross-coupling reactions remains extremely limited. Here, we report a rational strategy that provides a general entry to palladium-catalyzed Buchwald-Hartwig cross-coupling reactions in the solid state. The key finding of this study is that olefin additives can act as efficient molecular dispersants for the palladium-based catalyst in solid-state media to facilitate the challenging solid-state cross-coupling. Beyond the immediate utility of this protocol, our strategy could inspire the development of industrially attractive solvent-free palladium-catalyzed cross-coupling processes for other valuable synthetic targets.
  • Chemistry Letters 2018年10月 [査読有り][通常論文]
  • Koji Kubota, Peng Dai, Bradley L. Pentelute, Stephen L. Buchwald
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 140 8 3128 - 3133 2018年02月 [査読有り][通常論文]
     
    A new method for cysteine lysine cross-linking in peptides and proteins using palladium oxidative addition complexes is presented. First, a biarylphosphine-supported palladium reagent is used to transfer an aryl group bearing an O-phenyl carbamate substituent to a cysteine residue. Next, this carbamate undergoes chemoselective acyl substitution by a proximal lysine to form a cross-link. The linkage so formed is stable toward acid, base, oxygen, and external thiol nucleophiles. This method was applied to cross-link cysteine with nearby lysines in sortase A*. Furthermore, we used this method for the intermolecular cross-linking between a peptide and a protein based on the p53-MDM2 interaction. These studies demonstrate the potential for palladium-mediated methods to serve as a platform for the development of future cross-linking techniques for peptides and proteins with natural amino acid residues.
  • Biswas Souvagya, Kubota Koji, Orlandi Manuel, Turberg Mathias, Miles Dillon H, Sigman Matthew S, Toste F. Dean
    Angewandte Chemie-International Edition 57 2 589 - 593 2018年 [査読有り][通常論文]
  • Hayama Keiichi, Kubota Koji, Iwamoto Hiroaki, Ito Hajime
    CHEMISTRY LETTERS 46 12 1800 - 1802 2017年12月 [査読有り][通常論文]
  • Ryoto Kojima, Koji Kubota, Hajime Ito
    CHEMICAL COMMUNICATIONS 53 77 10688 - 10691 2017年10月 [査読有り][通常論文]
     
    We have developed a novel approach for the stereodivergent hydro-defluorination of gem-difluoroalkenes using copper(I) catalysts to obtain stereodefined monofluoroalkenes. Both (Z)- and (E)-terminal monofluoroalkenes were obtained by the hydrodefluorination of gem-difluoroalkenes in the presence of copper(I) catalysts and diboron or hydrosilane, respectively, with high stereoselectivity. DFT calculations were conducted to elucidate the stereoselectivity.
  • Hiroaki Iwamoto, Yu Ozawa, Koji Kubota, Hajime Ito
    JOURNAL OF ORGANIC CHEMISTRY 82 19 10563 - 10573 2017年10月 [査読有り][通常論文]
     
    The copper(I)-catalyzed regio- and stereoselective intramolecular alkylation of propargyl ethers and amines bearing an alkyl electrophilic moiety has been developed. The reaction showed high functional group tolerance and gave highly functionalized alkenylboronates bearing heterocyclic rings, which are versatile synthetic intermediates in organic chemistry. The borylation products can be transformed into multisubstituted alkenes through stereospecific transformations. Mechanistic studies showed that the chemo- and stereoselectivity of copper(I)-catalyzed borylation depends on the type of leaving group. Density functional theory calculations suggested that the regioselectivity of the borylcupration of the alkyne is controlled by the electronic effect of the oxygen atom of the propargyl ether in combination with the steric congestion between the boryl group and the substituent at the propargylic position.
  • Koji Kubota, Shun Osaki, Mingoo Jin, Hajime Ito
    Angewandte Chemie 129 23 6746 - 6650 Wiley-Blackwell 2017年06月 [査読有り][通常論文]
     
    A new method was developed for the first catalytic enantioselective borylation of aliphatic ketones. A variety of substrates reacted efficiently with bis(pinacolato)diboron in the presence of a copper(I)/chiral N-heterocyclic carbene complex catalyst to furnish optically active tertiary α-hydroxyboronates with moderate to high enantioselectivities (up to 94 % ee). Notably, the product could be converted into the chiral tertiary alcohol derivative using a stereospecific boron functionalization process. The theoretical study of the mechanism for the enantioselectivity is also described.
  • K. Kubota, Iwamoto, H. Ito
    ORGANIC & BIOMOLECULAR CHEMISTRY 15 2 285 - 300 2017年01月 [査読有り][通常論文]
     
    This review describes recent advances in direct borylation reactions of organic halides, including both transition-metal-catalyzed and metal-free methods. Since the pioneering work on palladium-catalyzed boryl substitution of aryl halides with a diboron compound reported by Miyaura and co-workers in 1995, various catalytic systems for the borylation of aryl, alkneyl, and alkyl halides have been developed to give a wide range of organoboronate esters that cannot be synthesized using conventional methods. Borylative cyclization of alkyl halides is also discussed.
  • Koji Kubota, Yuta Watanabe, Hajime Ito
    ADVANCED SYNTHESIS & CATALYSIS 358 15 2379 - 2384 2016年07月 [査読有り][通常論文]
     
    A novel approach has been developed for the synthesis of chiral 3-boryl-tetrahydroquinolines via the copper(I)-catalyzed regio- and enantioselective protoborylation of 1,2-dihydroquinolines, which were prepared by the partial reduction of the corresponding quinoline derivatives. This dearomatization/enantioselective borylation sequence has been used to provide a facile access to a wide variety of functionalized tetrahydroquinolines under mild conditions from readily available quinoline starting materials in combination with the stereospecific transformation of a stereogenic C-B bond. A theoretical study of the mechanism for the enantioselectivity of the reaction is also described.
  • Koji Kubota, Mingoo Jin, Hajime Ito
    ORGANOMETALLICS 35 10 1376 - 1383 2016年05月 [査読有り][通常論文]
     
    Density functional theory calculations were performed to validate the proposed reaction mechanism for the enantioselective nudeophilic borylation of a polarized C=O double bond in the presence of diphosphine/borylcopper(I) complexes. Consequently, we successfully elucidated the origin for the regioselectivity and the mechanism for the enantioselectivity of the reaction. We also obtained theoretical explanations for the fact that the presence of a proton source gave a higher reactivity and a better enantioselectivity in the borylation reaction of aldehydes with a copper(I)/(R)-DTBM-SEGPHOS complex catalyst. This study is particularly valuable toward the development and design of novel enantioselective borylation reactions with polarized carbon-heteroatom double bonds.
  • Koji Kubota, Yuta Watanabe, Keiichi Hayama, Hajime Ito
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 138 13 4338 - 4341 2016年04月 [査読有り][通常論文]
     
    We have developed a novel approach for the synthesis of enantio enriched 3-boryl-tetrahydropyridines via the Cu(I)-catalyzed regio-, diastereo-, and enantioselective protoborylation of 1,2-dihydropyridines, which were obtained by the partial reduction of the pyridine derivatives. This dearomatization/enantioselective borylation stepwise strategy provides facile access to chiral piperidines together with the stereospecific transformation of a stereogenic C-B bond from readily available starting materials. Furthermore, the utility of this method is demonstrated for the concise synthesis of the antidepressant drug (-)-paroxetine. A theoretical study of the reaction mechanism is also described.
  • Hiroaki Iwamoto, Koji Kubota, Hajime Ito
    CHEMICAL COMMUNICATIONS 52 35 5916 - 5919 2016年 [査読有り][通常論文]
     
    A new method has been developed for the Markovnikov hydroboration of alkyl-substituted terminal alkenes. Notably, the use of a bulky bisphosphine-copper(I) catalyst system resulted in high regioselectivity to afford secondary alkylboronates from the corresponding terminal alkenes (branch/linear = 92 : 8-97: 3). This method also exhibited good functional group compatibility.
  • Eiji Yamamoto, Ryoto Kojima, Koji Kubota, Hajime Ito
    SYNLETT 27 2 272 - 276 2016年01月 [査読有り][通常論文]
     
    Copper(I)-catalyzed diastereoselective borylative exo-cyclization of alkenyl ketones with bis(pinacolato)diboron is reported. The reaction of alkenyl aryl ketones under a CuCl/Xantphos catalyst system provides four- or five-membered-ring syn-2-(borylmethyl)cycloalkanol derivatives in good yields with high syn selectivities. The utility of this method is demonstrated by further transformations of the cyclic products.
  • Ho-Yan Sun, Koji Kubota, Dennis G. Hall
    CHEMISTRY-A EUROPEAN JOURNAL 21 52 19186 - 19194 2015年12月 [査読有り][通常論文]
     
    A method for enantioselective desymmetrization of 1,1-diborylalkanes through a stereoselective Pd-catalyzed Suzuki-Miyaura cross-coupling has been thoroughly optimized. The most effective ligand was found to be a alpha,alpha,alpha,alpha-tetra-aryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-derived phosphoramidite. Results show that in order to achieve high selectivity, a suitable balance between the sterics of the aryl groups and the amino group on the ligand must be achieved. While the base has been known to facilitate transme tallation in cross-coupling reactions, mechanistic studies on this desymmetrization process reveal that the base, in the presence of KHF2, likely plays an additional role in the hydrolysis of the pinacol boronates to the corresponding boronic acids. Through an in depth optimization of the chiral ligand and mechanistic studies, it was possible to obtain ee values over 90% for several aryl bromides and to develop a reliably scalable process (up to one gram of 1,1-diborylalkane substrate).
  • Koji Kubota, Keiichi Hayama, Hiroaki Iwamoto, Hajime Ito
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 54 30 8809 - 8813 2015年07月 [査読有り][通常論文]
     
    The enantioselective borylative dearomatization of a heteroaromatic compound has been achieved using a copper(I) catalyst and a diboron reagent. This reaction involves the regio- and enantioselective addition of active borylcopper(I) species to indole-2-carboxylates, followed by the diastereoselective protonation of the resulting copper(I) enolate to give the corresponding chiral indolines, which bear consecutive stereogenic centers.
  • Koji Kubota, Hiroaki Iwamoto, Eiji Yamamoto, Hajime Ito
    ORGANIC LETTERS 17 3 620 - 623 2015年02月 [査読有り][通常論文]
     
    Stereoselective silicon-tethered alkylboration of alkynes in the presence of a copper(I) catalyst and a diboron reagent provided the corresponding cyclic alkenylboronates in high yields (up to 99% yield) with excellent regio- and syn-selectivities (E/Z = <1:99). The products, which can be considered as the formal alkyne intermolecular alkylboration products, undergo subsequent selective derivatization, including ring opening, to give functionalized trans-stilbene derivatives.
  • Hiroaki Iwamoto, Koji Kubota, Eiji Yamamoto, Hajime Ito
    CHEMICAL COMMUNICATIONS 51 47 9655 - 9658 2015年 [査読有り][通常論文]
     
    The selective boryl substitution of alkyl halides bearing terminal C=C double bonds has been achieved using a copper(I)/tricyclohexylphosphine or copper(I)/o-diphenylphosphinophenol catalyst. This reaction represents a useful complementary approach to conventional procedures for the hydroboration of C=C double bonds or the borylative cyclization of alkyl halides bearing terminal alkenes.
  • Koji Kubota, Eiji Yamamoto, Hajime Ito
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 137 1 420 - 424 2015年01月 [査読有り][通常論文]
     
    The first catalytic enantioselective nucleophilic borylation of a C-O double bond has been achieved. A series of aldehydes reacted with a diboron reagent in the presence of a copper(I)/DTBM-SEGPHOS complex catalyst using MeOH as a proton source to give the corresponding optically active a-alkoxyorganoboronate esters with excellent enantioselectivities. Furthermore, the products could be readily converted to the corresponding functionalized chiral alcohol derivatives through stereospecific C-C bond forming reactions involving the stereogenic C-B bond.
  • Eiji Yamamoto, Yuta Takenouchi, Koji Kubota, Hajime Ito
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 72 7 758 - 769 2014年07月 [査読有り][通常論文]
     
    Transition-metal-catalyzed borylation has emerged as a powerful method for preparation of organoboron compounds, which are useful synthetic reagents in organic synthesis. However, chemo-, regio-, and stereoselective synthesis of the boron compounds are still highly required.Herein, we report copper (I)-catalyzed boryl substitution of allylic carbonates and ethers, monoborylation of 1,3-dienes and enynes, boryl substitution of alkyl halides, and borylative cyclization of alkenes containing an appropriate leaving group for the selective synthesis of various organoboron compounds including allyl- and allenylboronates, and optically active carbocyclic boronates. Preparation of the borylation products has been difficult with known procedures. In addition, direct enantio-convergent transformation of racemic substrates without a racemization or symmetrization process, a novel methodology for asymmetric synthesis with racemic substrates, is also reported.
  • Koji Kubota, Eiji Yamamoto, Hajime Ito
    ADVANCED SYNTHESIS & CATALYSIS 355 18 3527 - 3531 2013年12月 [査読有り][通常論文]
     
    An asymmetric monoborylation of alkenylsilanes catalyzed by a copper(I) complex with the chiral bisphosphine ligand BenzP* is reported. The reaction proceeded with excellent regioselectivity and high enantioselectivity to afford the corresponding optically active organoboronate esters with a stereogenic CB bond containing a vicinal silyl group. The synthetic utility of the product is demonstrated through stepwise transformations to multifunctional optically active compounds in a stereospecific manner.
  • Koji Kubota, Eiji Yamamoto, Hajime Ito
    Journal of the American Chemical Society 135 7 2635 - 2640 2013年02月20日 [査読有り][通常論文]
     
    A borylative exo-cyclization of alkenyl halides has been reported. The reaction includes the regioselective addition of a borylcopper(I) intermediate to unactivated terminal alkenes, followed by the intramolecular substitution of the resulting alkylcopper(I) moiety for the halide leaving groups. Experimental and theoretical investigations of the reaction mechanism have also been described. This reaction provides a new method for the synthesis of alkylboronates containing strained cycloalkyl structures from simple starting materials. © 2013 American Chemical Society.
  • Hajime Ito, Koji Kubota
    ORGANIC LETTERS 14 3 890 - 893 2012年02月 [査読有り][通常論文]
     
    Borylation of alkyl halides with diboron proceeded in the presence of a copper(I)/Xantphos catalyst and a stoichiometric amount of K(O-t-Bu) base. The boryl substitution proceeded with normal and secondary alkyl chlorides, bromides, and iodides, but alkyl sulfonates did not react. Menthyl halides afforded the corresponding borylation product with excellent diastereoselectivity, whereas (R)-2-bromo-5-phenylpentane gave a racemic product. Reaction with cyclopropylmethyl bromide resulted in ring-opening products, suggesting the reaction involves a radical pathway.

MISC

担当経験のある科目(授業)

  • 物質変換工学北海道大学
  • 化学英語北海道大学
  • 応用化学学生実験IV北海道大学
  • 応用化学学生実験IV北海道大学

共同研究・競争的資金等の研究課題

  • 固相メカノラジカルの化学と応用
    国立開発研究法人 科学技術振興機構 (JST):創発的研究支援事業
    研究期間 : 2021年04月 -2024年03月
  • 不溶性有機化合物の自在化学変換を可能とする革新的メカノケミカル合成
    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 : 2021年04月 -2024年03月 
    代表者 : 久保田 浩司
  • ハイブリッド型メカノレドックス触媒系による固体有機合成
    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 : 2020年04月 -2022年03月 
    代表者 : 久保田 浩司
  • 固体内クロスカップリングによるナノグラフェンの固相精密合成
    科研費「若手研究」:
    研究期間 : 2019年04月 -2021年03月 
    代表者 : 久保田 浩司
  • ラセミ体ハロゲン化アルキルを基質としたエナンチオ収束型不斉ホウ素置換反応の開発
    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 : 2014年04月 -2017年03月 
    代表者 : 久保田 浩司
     
    ■ ヘテロ芳香族化合物の脱芳香族化/不斉ホウ素化 ■ < Kubota, K.; Watanabe, Y.; Hayama, K.; Ito, H. J. Am. Chem. Soc. 2016, 138, 4338.> 入手容易なピリジンを原料とする不斉反応は、多くの医薬品の中核をなす光学活性ピペリジンを与える有用な手法である。本研究では、ピリジンの部分還元により得られる1,2-ジヒドロピリジンに対し、不斉銅(I)触媒存在下、ジボロンを作用させると光学活性ボリルピペリジンが高立体選択的に得られることを見出した。また同様の触媒系はキノリンにも適用可能であり、別報として報告した。 ■ 脂肪族および芳香族アルデヒド類の求核的不斉ホウ素化反応の機構解明 ■ < Kubota, K.; Jin, M.; Ito, H. Organometallics 2016, 35, 136.> 我々は以前、銅(I)触媒を用いたアルデヒド類のエナンチオ選択的ホウ素化反応を報告した。本研究では、理論計算により、位置選択性やエナンチオ選択性発現機構をはじめとする反応の詳細を明らかにし、今後の反応設計における重要な知見が得られた。 ■ キラルアニオン相間移動触媒による不斉プメラー反応の開発 ■ < Kubota, K.; Biswas. S; Turberg, M. Dean F. Toste, Manuscript under preparation> チオニウムカチオンへの付加反応を経由するプメラー型変換反応は、含硫黄化合物を合成する上で有用な手法である。本研究では、キラルアニオン相関移動触媒を用いることで酸化的不斉プメラー反応の開発に初めて成功した。


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