Developement of enantio and regioselective haogenation

• Project/Area Number: 17K08210
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Osaka University
• Principal Investigator: Murai Kenichi 大阪大学, 薬学研究科, 講師 (70532068)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ハロゲン化 / シクロプロパン / ボリル化 / 不斉反応 / 位置選択性 / 合成化学 / 有機化学

Outline of Final Research Achievements

We studied (1) enantioselective desymmetric halo-esterification reaction using trisimidazoline catalyst, (2) regioselective halogenation reaction of aromatic compounds using Lewis base catalysts, and (3) 1,3-bifunctionalization of cyclopropanes. Although our initial goal in developing a selective halogenation reaction has not been achieved, we succeeded in finding 1,3-arylboration of arylcyclopropane. It was found that 1,3-arylboration of arylcyclopropane proceeds successfully by treatment with boron trichloride in the presence of electron-rich aromatic compounds. Formal 1,3-oxyaryllation and 1,3-aminoaryllation were also achieved as the application of this method.

Academic Significance and Societal Importance of the Research Achievements

求電子剤を用いるシクロプロパンの官能基化は合成シントンとして有用な1,3-官能基化化合物を与える重要な変換反応である。これまで様々な手法が報告されているが、活性化されていないシクロプロパンの1,3-アリールホウ素化はこれまでに報告例がなかった。今回見出した手法は、電子豊富芳香環化合物共存下に三塩化ホウ素で処理するというシンプルな反応であり、後処理法を工夫することで形式的な1,3-オキシアリール化、1,3-アミノアリールも達成した。後者のふたつの変換もこれまでに報告はなく、シクロプロパンの新しい官能基化反応は学術的に意義深い。

Research Products

• [Journal Article] Total Synthesis and Biological Evaluation of the Potent HIV Latency-Reversing Agent Ansellone A and its Analogues (2021)
  • Author(s): Mizushi Yanagihara, Kenichi Murai*, Naoki Kishimoto, Towa Abe, Shogo Misumi, and Mitsuhiro Arisawa*
  • Journal Title: Org. Lett. Volume: 23 Issue: 5 Pages: 1720-1725
  • DOI: 10.1021/acs.orglett.1c00151
  • Peer Reviewed
• [Journal Article] Selective Reduction of α,β-Unsaturated Weinreb Amides in the Presence of α,β-Unsaturated Esters (2020)
  • Author(s): Morita Kenta、Murai Kenichi、Arisawa Mitsuhiro、Fujioka Hiromichi
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 68 Issue: 11 Pages: 1100-1103
  • DOI: 10.1248/cpb.c20-00545
  • NAID: 130007933575
  • ISSN: 0009-2363, 1347-5223
  • Year and Date: 2020-11-01
  • Peer Reviewed / Open Access
• [Journal Article] Thermal [2 + 2]-cycloaddition between silylalkynes and allenylphenols followed by the nucleophilic addition of water: metal-free and economical synthesis of arylcyclobutenals (2020)
  • Author(s): Ohno Shohei、Avena Ramon Francisco、Aoyama Hiroshi、Fujioka Hiromichi、Arisawa Mitsuhiro
  • Journal Title: Green Chemistry Volume: 22 Issue: 4 Pages: 1220-1228
  • DOI: 10.1039/c9gc04184b
  • Peer Reviewed / Open Access
• [Journal Article] Absorption, Fluorescence, and Two-Photon Excitation Ability of 5-Phenylisolidolo[2,1-a]quinolines (2020)
  • Author(s): Avena Ramon Francisco、Qiao Lin、Fujii Yuki、Otomo Kohei、Ishii Hirokazu、Suzuki Takeyuki、Tsujino Hirofumi、Uno Tadayuki、Tsutsumi Yasuo、Kawashima Yusuke、Takagi Tatsuya、Murai Kenichi、Nemoto Tomomi、Arisawa Mitsuhiro
  • Journal Title: ACS Omega Volume: 5 Issue: 5 Pages: 2473-2479
  • DOI: 10.1021/acsomega.9b04070
  • Peer Reviewed / Open Access
• [Journal Article] Design and Synthesis of 1,2-Deoxy-pyranose Derivatives of Spliceostatin A toward Prostate Cancer Treatment (2020)
  • Author(s): Yoshikawa Yusuke、Ishibashi Airi、Takehara Tsunayoshi、Suzuki Takeyuki、Murai Kenichi、Kaneda Yasufumi、Nimura Keisuke、Arisawa Mitsuhiro
  • Journal Title: ACS Medicinal Chemistry Letters Volume: as soon as Issue: 6 Pages: 1310-1315
  • DOI: 10.1021/acsmedchemlett.0c00153
  • Peer Reviewed / Open Access
• [Journal Article] Iridium-Catalyzed Intramolecular Cycloisomerization between Functionalized Alkyne with Aryl Vinyl Ether: Synthesis of 2-Vinyl-3-functionalized Methylbenzofurans (2020)
  • Author(s): Qiu Jiawei、Ohno Shohei、Matsuzaki Tsuyoshi、Suzuki Takeyuki、Murai Kenichi、Arisawa Mitsuhiro
  • Journal Title: The Journal of Organic Chemistry Volume: 85 Issue: 15 Pages: 10198-10205
  • DOI: 10.1021/acs.joc.0c00954
  • Peer Reviewed
• [Journal Article] Ring-opening 1,3-arylboration of arylcyclopropanes mediated by BCl3 (2020)
  • Author(s): Yuichi Kuboki, Mitsuhiro Arisawa, Kenichi Murai*
  • Journal Title: RSC Adv. Volume: 10 Issue: 62 Pages: 37797-37799
  • DOI: 10.1039/d0ra08151e
  • Peer Reviewed / Open Access
• [Journal Article] Oxidative Rearrangement of Primary Amines Using PhI(OAc)2 and Cs2CO3 (2019)
  • Author(s): Wataru Yamakoshi, Mitsuhiro Arisawa, Kenichi Murai
  • Journal Title: Organic Letters Volume: 21 Issue: 9 Pages: 3023-3027
  • DOI: 10.1021/acs.orglett.9b00559
  • Peer Reviewed
• [Journal Article] Chemoselective Transformations of Aromatic Methoxymethyl Ethers Using Trialkylsilyl Triflate and 2,2’-Bipyridyl (2019)
  • Author(s): Mizushi Yanagihara, Reiya Ohta, Kenichi Murai, Mitsuhiro Arisawa, Hiromichi Fujioka
  • Journal Title: ACS Omega Volume: 4 Issue: 5 Pages: 8465-8471
  • DOI: 10.1021/acsomega.9b00643
  • Peer Reviewed / Open Access
• [Journal Article] Pd-catalyzed Migratory Cycloisomerization of N-Allyl-o-allenylaniline Derivatives (2019)
  • Author(s): Yasuhiro Ii, Satoru Hirabayashi, Shohei Yoshioka, Hiroshi Aoyama, Kenichi Murai, Hiromichi Fujioka, Mitsuhiro Arisawa
  • Journal Title: Org. Lett. Volume: 21 Issue: 10 Pages: 3501-3504
  • DOI: 10.1021/acs.orglett.9b00676
  • Peer Reviewed
• [Journal Article] Ligand-free Suzuki Miyaura coupling reaction of aryl chloride using a continuous irradiation type microwave and palladium nanoparticle catalyst: Effect of a co-existing solid (2019)
  • Author(s): Makito Yamada, Yasunori Shio, Toshiki Akiyama, Tetsuo Honma, Yuuta Ohki, Naoyuki Takahashi, Kenichi Murai, Mitsuhiro Arisawa
  • Journal Title: Green Chem. Volume: 21 Issue: 16 Pages: 4541-4549
  • DOI: 10.1039/c9gc01043b
  • Peer Reviewed / Open Access
• [Journal Article] Direct Synthesis of Dialkylaryl-vinylsilane Derivatives: Metathesis of Dialkylaryl-iso-propenylsilane and Its Application to Tetracyclic Silacycle Dye Synthesis (2019)
  • Author(s): Shohei Yoshioka, Tsunayoshi Takehara, Tsuyoshi Matsuzaki, Takeyuki Suzuki, Hirofumi Tsujino, Tadayuki Uno, Yasuo Tsutsumi, Kenichi Murai, Hiromichi Fujioka, Mitsuhiro Arisawa
  • Journal Title: Chemical Communications, Volume: 55 Issue: 93 Pages: 14070-14073
  • DOI: 10.1039/c9cc06777a
  • Peer Reviewed
• [Journal Article] Discovery and structure-activity relationship of imidazolinylindole derivatives as kallikrein 7 inhibitors (2019)
  • Author(s): Murafuji, Hidenobu; Muto, Tsuyoshi; Goto, Megumi; Imajo, Seiichi; Sugawara, Hajime; Oyama, Yoshiaki; Minamitsuji, Yutaka; Miyazaki, Shuji; Murai, Kenichi; Fujioka, Hiromichi
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 29 Issue: 2 Pages: 334-338
  • DOI: 10.1016/j.bmcl.2018.11.011
  • Peer Reviewed
• [Journal Article] Highly Discriminative and Chemoselective Deprotection/Transformations of Acetals with the Combination of Trialkylsilyl Triflate/2,4,6-Collidine (2018)
  • Author(s): Reiya Ohta, Nao Matsumoto, Yoshifumi Ueyama, Yuichi Kuboki, Hiroshi Aoyama, Kenichi Murai, Mitsuhiro Arisawa, Tomohiro Maegawa, Hiromichi Fujioka
  • Journal Title: JOURNAL OF ORGANIC CHEMISTRY Volume: 83 Issue: 12 Pages: 6432-6443
  • DOI: 10.1021/acs.joc.8b00675
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Design and Synthesis of N1,N8-Diacetylspermidine Analogues having a Linker with Desired Functional Groups (2018)
  • Author(s): Reiya Ohta, Akihiro Oguro, Kazuhiro Nishimura, Kenichi Murai, Hiromichi Fujioka, Mitsuhiro Arisawa.
  • Journal Title: Organic & Biomolecular Chemistry Volume: 17 Issue: 4 Pages: 867-875
  • DOI: 10.1039/c8ob02900h
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Reusable Immobilized Iron(II) Nanoparticle Pre-Catalysts for Ligand-Free Kumada Coupling (2018)
  • Author(s): Toshiki Akiyama, Yuki Wada, Kellie Jenkinson, Tetsuo Honma, Kazuki Tsuruta, Yusuke Tamenori, Hitoshi Haneoka, Tsunayoshi Takehara, Takeyuki Suzuki, Kenichi Murai, Hiromichi Fujioka, Yoshihiro Sato, Andrew E. H. Wheatley, Mitsuhiro Arisawa
  • Journal Title: Acs Applied Nano Materials Volume: 1 Issue: 12 Pages: 6950-6958
  • DOI: 10.1021/acsanm.8b01742
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Oxidative Rearrangement of Secondary Amines using Hypervalent Iodine (III) Reagent (2018)
  • Author(s): Kenichi Murai、Tetsuya Kobayashi、Makoto Miyoshi、Hiromichi Fujioka
  • Journal Title: Organic Letters Volume: 20 Issue: 8 Pages: 2333-2337
  • DOI: 10.1021/acs.orglett.8b00675
  • Peer Reviewed
• [Journal Article] Total Synthesis of Terpenoids Employing a “Benzannulation of Carvone” Strategy: Synthesis of (－)-Crotogoudin (2017)
  • Author(s): Peter Finkbeiner, Kenichi Murai, Michael Ropke, Richmond Sarpong
  • Journal Title: J. Am. Chem. Soc. Volume: 139 Issue: 33 Pages: 11349-11352
  • DOI: 10.1021/jacs.7b06823
• [Journal Article] Enantio- and Diastereoselective Betti/aza-Michael Sequence: Single Operated Preparation of Chiral 1,3-Disubstituted Isoindolines (2017)
  • Author(s): Takizawa Shinobu、Sako Makoto、Abozeid Mohamed Ahmed、Kishi Kenta、Wathsala H. D. P.、Hirata Shuichi、Murai Kenichi、Fujioka Hiromichi、Sasai Hiroaki
  • Journal Title: Organic Letters Volume: 19 Issue: 19 Pages: 5426-5429
  • DOI: 10.1021/acs.orglett.7b02693
  • Peer Reviewed / Int'l Joint Research
• [Presentation] ワンポット閉環メタセシス/酸化/1,3-双極子環化付加反応を用いた多置換イソインドロ[2,1-a]キノリンの合成とその吸光・蛍光特性 (2020)
  • Author(s): （1 阪大院薬・2 生理学研究所） 〇和田祐希 1・Ramon Francisco Avena 1・藤居由基 1・大友康平 2・石井宏和 2・村井健一 1・根本知己 2・有澤光弘 1
  • Organizer: 第49回複素環化学討論会
• [Presentation] (+)-シンコナミノンの全合成・絶対構造決定・生物活性評価 (2020)
  • Author(s): (阪大院薬 a、慶大薬 b)○佐藤祐太 a、及部奈緒子 a、鈴木小夜 b、村井健一 a、中村智徳 b、有澤光弘 a
  • Organizer: 第62回天然有機化合物討論会
• [Presentation] アリールシクロプロパンの1,3－アリールボリル化反応の開発 (2020)
  • Author(s): 窪木 勇一、有澤 光弘、村井 健一
  • Organizer: 第70回日本薬学会関西支部大会 (WEB)
• [Presentation] Ni 触媒による炭素－酸素結合の切断/生成を伴う環化異性化反応;2,3-ジ置換ベンゾフランの合成 (2020)
  • Author(s): （阪大院薬）○大野祥平，Qiu Jiawei，田中志幸，村井健一，有澤光弘
  • Organizer: 第46回反応と合成の進歩シンポジウム
• [Presentation] アミン化合物の特性を活かした酸化的転位反応とC3対称トリスイミダゾリン触媒の開発 (2020)
  • Author(s): 村井健一
  • Organizer: 第46回反応と合成の進歩シンポジウム
  • Invited
• [Presentation] 超原子価ヨウ素試薬を用いる２，２－二置換環状アミン化合物の環縮小反応 (2020)
  • Author(s): ○三好 諒1、佐古 真1、有澤 光弘1、村井 健一1 (1. 阪大院薬)
  • Organizer: 日本薬学会第141年会
• [Presentation] 不活性シクロプロパンの開環を伴う1,3‐アリールボレーションの開発 (2020)
  • Author(s): 窪木勇一、有澤光弘、村井健一
  • Organizer: 日本薬学会第140年会
• [Presentation] Ansellone Aの合成研究 (2020)
  • Author(s): 柳原瑞士、有澤光弘、村井健一
  • Organizer: 日本薬学会第140年会
• [Presentation] "Chemoselective Transformations of Aromatic Methoxymethyl Ethers Using Trialkylsilyl Triflate and 2,2’-Bipyridyl " (2019)
  • Author(s): Mizushi Yanagihara *, Reiya Ohta, Kenichi Murai, Mitsuhiro Arisawa, Hiromichi Fujioka
  • Organizer: 第4回プロセス化学国際シンポジウム (ISPC 2019)
  • Int'l Joint Research
• [Presentation] 超原子価ヨウ素試薬を用いる第二級アミンの酸化的転位反応 (2019)
  • Author(s): 三好諒、小林哲也、藤岡弘道、有澤光弘、村井健一
  • Organizer: 第39回有機合成若手セミナー
• [Presentation] Efficient Synthesis of N-Trifluoromethylthiomethyl Indoles: Physical Property, Metabolism and IDO Inhibitory Activity Evaluation of Substituted Indoles (2019)
  • Author(s): Yuichi Kuboki, Mitsuhiro Arisawa, Katsumi Ohta , Akira Asai , Hiromichi Fujioka
  • Organizer: 国際複素環化学会議（ISHC-27）
• [Presentation] Oxidative Rearrangement of Secondary Amines Using Hypervalent Iodine(III) Reagent (2019)
  • Author(s): Makoto Miyoshi, Tetsuya Kobayashi, Hiromichi Fujioka, Mitsuhiro Arisawa, Kenichi Murai
  • Organizer: 国際複素環化学会議（ISHC-27）
  • Int'l Joint Research
• [Presentation] 連続照射型マイクロ波とガラス担持型Pdナノ粒子触媒を用いた塩化アリール誘導体のリガンドフリー鈴木ー宮浦カップリング反応の開発 (2019)
  • Author(s): 山田真希人, 秋山敏毅, 大木裕太, 高橋直行, 本間徹生, 村井健一, 有澤光弘
  • Organizer: 日本化学会第99春季年会(2020)
• [Presentation] 超原子価ヨウ素試薬を用いた第一級アミンの酸化的転位反応の開発 (2019)
  • Author(s): 山腰航, 有澤光弘, 村井健一
  • Organizer: 日本化学会第99春季年会(2019)
• [Presentation] ニッケルナノ粒子触媒を用いたハロゲン化アリールと有機金属反応剤のリガンドフリーC(sp2)-C(sp3)クロスカップリング反応の開発 (2019)
  • Author(s): 四尾康徳, 秋山敏毅, 本間徹生, 村井健一, 佐藤美洋, 有澤光弘
  • Organizer: 日本化学会第99春季年会(2020)
• [Presentation] ルテニウムナノ粒子触媒を用いたアミノ基上のN-allyloxycarbonyl基除去法の開発 (2019)
  • Author(s): 平林怜, 秋山敏毅, 本間徹生, 佐藤美洋, 村井健一, 有澤光弘
  • Organizer: 日本薬学会第139年会
• [Presentation] イリジウム触媒を用いたアリールエノールエーテルとシリルアルキンの環化異性化反応―２,３ジ置換ベンゾフランの合成― (2019)
  • Author(s): Qiu Jiawei, 大野将平, 村井健一, 有澤光弘
  • Organizer: 日本薬学会第139年会
• [Presentation] 超原子価ヨウ素試薬を用いる１級アミンの酸化的転位反応 (2019)
  • Author(s): 山腰航, 有澤光弘, 村井健一
  • Organizer: 日本薬学会第139年会
• [Presentation] ３価のヨウ素試薬を用いるアミン類の酸化的転位反応 (2018)
  • Author(s): 村井健一, 小林哲也, 三好 諒, 有澤光弘, 藤岡弘道
  • Organizer: 第49回 複素環化学討論会
• [Presentation] 多環式含ケイ素6員環化合物のワンポット合成と複数回Diels-Alder反応の開発 (2018)
  • Author(s): 吉岡祥平, 村井健一, 藤岡健一, 藤岡 弘道, 有澤 光弘
  • Organizer: 第49回 複素環化学討論会
• [Presentation] 多置換５－メチルイソインドロキノリンの合成とその吸光・蛍光特性 (2018)
  • Author(s): 和田祐希, 藤居由基, 嵩原綱吉, 鈴木健之, 村井健一, 藤岡弘道, 有澤光弘
  • Organizer: 第68回日本薬学会近畿支部総会・大会
• [Presentation] Ni触媒を用いたビニルエーテルの分子内C-O結合切断－C-C結合形成反応 (2018)
  • Author(s): 大野祥平、村井健一、藤岡弘道、有澤光弘
  • Organizer: 第68回日本薬学会近畿支部総会・大会
• [Presentation] アミン化合物の酸化的転位反応 (2018)
  • Author(s): 村井健一
  • Organizer: 第4回近畿薬学シンポジウム：化学系の若い力
  • Invited
• [Presentation] Synthesis of 5-phenylisoindolo[2,1-a]quinoline and isoindolo[1,2-a]isoquinoline dyes with unique photochemical properties via one-pot ring-closing metathesis/1,3-dipolar cycloaddition reaction (2018)
  • Author(s): Avena Ramon, 藤居由基, 嵩原綱吉, 鈴木健之, 村井健一, 藤岡弘道, 有澤光弘
  • Organizer: 第68回日本薬学会近畿支部総会・大会
• [Presentation] アプタマー取得に向けたポリアミン誘導体の設計と合成 (2018)
  • Author(s): 太田礼伊也, 小黒明広, 西村和洋, 村井健一, 藤岡弘道, 有澤光弘
  • Organizer: 第44回反応と合成の進歩シンポジウム
• [Presentation] Ni-Catalyzed C-O Bond Cleavage of 3-Phenoxy Acrylic Acid Derivatives and Subsequent Intramolecular C-C Bond Formation; Synthesis of 2,3-Disubstituted Benzofurans (2018)
  • Author(s): Shohei Ohno, Kenichi Murai, Hiromichi Fujioka, Mitsuhiro Arisawa
  • Organizer: 8th Spanish-Portuguese-Japanese Organic Chemistry Symposium (8th SPJ-OCS)
• [Presentation] Chemoselective Transformations of Aromatic Methoxymethyl Ethers with Combination of Trialkylsilyl Trifrate and 2,2’-Bipyridyl (2018)
  • Author(s): Mizushi Yanagihara, Reiya Ohta, Kenichi Murai, Mitsuhiro Arisawa, Hiromichi Fujioka
  • Organizer: IKCOC-14
• [Presentation] Synthesis and Optical Feature of Multi-Substituted Isoindoro[2,1-a]quinoline (2018)
  • Author(s): Yuki Wada, Yuki Fujii, Tsunayoshi Takehara, Takeyuki Suzuki, Kenichi Murai, Hiromichi Fujioka, Mitsuhiro Arisawa
  • Organizer: IKCOC-14
• [Presentation] Self-assembled Pd-nanoparticles Catalyzed Reactions (2018)
  • Author(s): Satoru Hirabayashi, Mincen Xiao, Toshiaki Akiyama, Makito Yamada, Kenichi Murai, Hiromichi Fujioka, Mitsuhiro Arisawa
  • Organizer: IKCOC-14
• [Presentation] 有機分子触媒 による 1,3-cis- イソインドリン 化合物の エナンチオ選択的ワンポット合成 (2018)
  • Author(s): ○ Wathsala H.D.P., 滝澤忍, 佐古真, 岸鉄馬 , 平田修一, 村井健一, 藤岡弘道, 笹井 宏明
  • Organizer: 日本薬学会 第138回年会
• [Presentation] 芳香族メトキシメチルエーテルの穏和な脱保護法 (2018)
  • Author(s): ○柳原瑞士, 太田礼伊也, 村井健一, 有澤光弘, 藤岡弘道
  • Organizer: 日本薬学会 第138回年会
• [Presentation] 超原子価ヨウ素試薬を用いるテトラヒドロ‐β‐カルボリン化合物の酸化的転位反応 (2017)
  • Author(s): ○村井健一、小林哲也、松浦 螢、三好 涼、藤岡弘道
  • Organizer: 第20回ヨウ素学会シンポジウム
• [Presentation] Oxidative rearrangement reactions of spiro amine compounds using PhI(OAc)2 (2017)
  • Author(s): Kenichi Murai、○Tetsuya Kobayashi、Ryo Miyoshi、Hiromichi Fujioka
  • Organizer: HALCHEM VIII
• [Presentation] スピロアミン化合物の酸化的転位反応 (2017)
  • Author(s): ○村井健一、小林哲也、松浦螢、三好諒、青山浩、藤岡弘道
  • Organizer: 第43回 反応と合成の進歩シンポジウム
• [Presentation] 超原子価ヨウ素試薬を用いる酸化的転移反応による含窒素化合物合成法の開発 (2017)
  • Author(s): 村井健一、〇小林哲也、三好諒、藤岡弘道
  • Organizer: 第112回有機合成シンポジウム