New synthesis of a seven member ring fused heterocycles using ring expansion reaction of an aromatic ring

• Project/Area Number: 19590009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: AOYAMA Toyohiko Nagoya City University, 大学院・薬学研究科, 教授 (80080191)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ヘテロ環化学 / トリメチルシリルジアゾメタン / アルキリデンカルベン / アリールアセチレン / アリールプロピオレート / ピロリジン / β-アミノケトン / アリール(オキソ)アセテート / インダゾール / [3+2]環化付加反応 / t-ブチル(2-メトキシフェニィル)(オキソ)アセテート / ベンゾフラン-3-カルボキシレート / Buchner反応 / 2-アザアズレン / 2-ジアゾ-2-トリメチルシリルエタノール / ピラゾール

Research Abstract

(1) Ketones reacted with magnesium bromide salt of trimethylsilyldiazomethane (TMSCHN_2) to give the corresponding 2-diazo-2-(trimethylsilyl)ethanols which were easily converted to pyraazoles by 1,3-dipole cycloaddition the reaction with acetylenes. (2) Aryl and heteroaryl aldehydes were easily converted to functionalized acetykenes in on-pot using lithium salt of TMSCHN_2. (3) TMSCHN_2 reacted with thiobenzoyl isocyanates to give the corresponding diazoketones which were converted to 2-azaazulenes by treatment with rhodium acetates. (4) Diazo(trimethylsilyl)methylmagnesium bromide smoothly reacted with t-butyl aryl(oxo)acetates to afford the corresponding arylpropiolates via alkylidenecarbene intermediates. (5) Diazo(trimethylsilyl)methylmagnesium bromide readily reacted with ketones and aldehydes to give 2-diazo-(2-trimethylsilyl)ethanoles which were efficiently converted to indazoles bearing a hydroxmethyl unit at 3-position by intermolecular [3+2]cycloaddition with benzynes. (6) Diazo(trimethylsilyl)methylmagnesium bromide reacted with (o-methoxyphenyl)(oxo)acetates to readily afford 2-unsubstituted benzofuran-3-carboxylates via oxonium ylides formed from the initially generated alkylidenecarbene intermediates. (7) Lithium trimethylsilyldiazomethane reacted with N-benzyl-β-aminoketones at -78℃in THF to give 3-substituted 1-benzyl-3-(trimethylsiloxy)pyrrolidines in moderate to good yields.

Research Products

• [Journal Article] Synthesis of 3-substituted 3-(trimethylsiloxy)pyrrolidines from β-aminoketones and lithium trimethylsilyldiazomethane (2010)
  • Author(s): Yoshiyuki Hari, Takuya Yokoyama, Toyohiko Aoyama
  • Journal Title: Heterocycles Vol.80 Pages: 679-687
  • NAID: 40016900140
  • Peer Reviewed
• [Journal Article] Synthesis of 3-substituted 3-(trimethylsiloxy)pyrroridines from β-aminoketones and lithium trimethylsilyldiazomethane (2010)
  • Author(s): Yoshiyuki Hari, Takuya Yokoyama, Toyohiko Aoyama
  • Journal Title: Heterocycles 80 Pages: 679-687
  • Peer Reviewed
• [Journal Article] Facile synthesis of 2-unsubstituted benzofuran-3-carboxylates using diazo(trimethylsilyl)methylmagnesium bromide (2009)
  • Author(s): Yoshiyuki Hari, Ryousuke Kondo, Koji Date, Toyohiko Aoyama
  • Journal Title: Tetrahedron Vol.65 Pages: 8708-8713
  • Peer Reviewed
• [Journal Article] Facile two-step synthesis of 3-substituted indazoles using diazo(trimethylsilyl)methylmagnesium bromide (2009)
  • Author(s): Yoshiyuki Hari, Ryousuke Sone, Toyohiko Aoyama
  • Journal Title: Org. Biomol. Chem Vol.7 Pages: 2804-2808
  • Peer Reviewed
• [Journal Article] Facile two-step synthesis of 3-substituted indazoles using diazo(trimethylsilyl)methylmagnesium bromide (2009)
  • Author(s): Yoshiyuki Hari, Ryousuke Sone, Toyohiko Aoyama
  • Journal Title: Org.Biomol.Chem. 7 Pages: 2804-2808
  • Peer Reviewed
• [Journal Article] Facile synthesis of 2-unsubstituted benzofuran-3-carboxylates using diazo(trimethylsilyl)methylmagnesium bromide (2009)
  • Author(s): Yoshiyuki Hari, Ryousuke Kondo, Koji Date, Toyohiko Aoyama
  • Journal Title: Tetrahedron 65 Pages: 8708-8713
  • Peer Reviewed
• [Journal Article] New synthesis of t-butyl arylpropiolates using diazo(trimethylsilyl)methylmagnesiu bromide (2008)
  • Author(s): Yoshiyuki Hari, Koji Date, Ryousuke Kondo, Toyohiko Aoyama
  • Journal Title: Tetrahedron Lett. Vol.49 Pages: 4965-4967
  • Peer Reviewed
• [Journal Article] Facile synthesis of 2-azaazulenes from thiobenzoyl isocyanates using trimethylsilyldiazomethane (2008)
  • Author(s): Mikio Morita, Yoshiyuki Hari, Tomoe Iguchi, Toyohiko Aoyama
  • Journal Title: Tetrahedron Vol.64 Pages: 1753-1758
  • Peer Reviewed
• [Journal Article] New Synthesis of t-Butyl Arylpropiolates Using Diazo (trimethylsilyl) methylmagnesium Bromide (2008)
  • Author(s): Y. Hari, K. Date. R. Kondo, Toyohiko Aoyama
  • Journal Title: Tetrahedron Lett. 49 Pages: 4965-4967
  • Peer Reviewed
• [Journal Article] Facile synthesis of 2-azaazulenes from thiobenzoyl isocyanates using trim ethylsilydiazomethane (2008)
  • Author(s): M. Morita, Y. Hari, T. Iguchi, T. Aoyama
  • Journal Title: Tetrahedro 64 Pages: 1753-1758
  • Peer Reviewed
• [Journal Article] Facile One-Pot Synthesis of Functionalized Acetylenes from Aryl and Heteroaryl Aldehydes Using Lithium Trimethylsilyldiazomethane (2007)
  • Author(s): Yoshiyuki Hari, Koji Date, Toyohiko Aoyama
  • Journal Title: Heterocycles Vol.74 Pages: 545-552
  • NAID: 40015919610
  • Peer Reviewed
• [Journal Article] An Efficient Synthesis of 2-diazo-2-(trimethylsilyl)ethanols and their application to pyrazole synthesis (2007)
  • Author(s): Yoshiyuki Hari, Susumu Tsuchida, Ryousuke Sone, Toyohiko Aoyama
  • Journal Title: Synthesis Pages: 3371-3375
  • Peer Reviewed
• [Journal Article] An efficient synthesis of 2-diazo-2(trimethylsilyl)ethanols and their application to pyrazole synthesis (2007)
  • Author(s): Y. Hari, S. Tsuchida, R. Sone, T. Aoyama
  • Journal Title: Synthesis Pages: 3371-3375
  • Peer Reviewed
• [Presentation] Facile synthesis of 3-substituted pyrazoles and indazoles using [3+2]cycloaddition reactions of 2-diazo-2-(trimethylsilyl)ethanols (2009)
  • Author(s): Yoshiyuki Hari, Ryousuke Sone, Toyohiko Aoyama
  • Organizer: 第22回国際複素環化学会議(ICHC-22)
  • Place of Presentation: セントジョーンズ、カナダ
  • Year and Date: 2009-08-27
• [Presentation] トリメチルシリルジアゾメタンのLi塩を用いた新規なピロリジン合成 (2009)
  • Author(s): 横山拓也, 張功幸, 青山豊彦
  • Organizer: 第35回反応と合成の進歩シンポジウム
  • Place of Presentation: 金沢
• [Presentation] リチウムトリメチルシリルジアゾメタンを用いたキラル2-置換-3-ピロリン-2-カルボキシラート類の立体選択的合成 (2009)
  • Author(s): 稲葉綾子, 張功幸, 青山豊彦
  • Organizer: 第35回反応と合成の進歩シンポジウム
  • Place of Presentation: 金沢
• [Presentation] トリメチルシリルジアゾメタンのMgBr塩を用いたα-ヒドロキシアシルシランの合成 (2009)
  • Author(s): 曽根良介, 張功幸, 青山豊彦
  • Organizer: 第35回反応と合成の進歩シンポジウム
  • Place of Presentation: 金沢
• [Presentation] トリメチルシリルジアゾメタンのMgBr塩を用いた3-置換インダゾール合成 (2008)
  • Author(s): 曽根良介, 張功幸, 青山豊彦
  • Organizer: 第38回複素環化学討論会
  • Place of Presentation: 福山
• [Presentation] トリメチルシリルジアゾメタンのMgBr塩を用いたベンゾフラン-3-カルボキシラート類の合成 (2008)
  • Author(s): 近藤良祐, 張功幸, 青山豊彦
  • Organizer: 第38回複素環化学討論会
  • Place of Presentation: 福山
• [Presentation] トリメチルシリルジアゾメタンのMgBr塩を用いた塩を用いたベンゾフラン-3-カルボキシラート類の合成 (2008)
  • Author(s): 近藤良祐, 張功幸, 青山彦
  • Organizer: 第38回複素環化学討論会
  • Place of Presentation: 福山
• [Presentation] トリメチルシリルジアゾメタンとチオベンゾイルイソシアナート類の反応による2-アザアズレン類の新規合成 (2007)
  • Author(s): 森田幹雄, 張功幸, 青山豊彦
  • Organizer: 複素環化学討論会
  • Place of Presentation: 長野市
  • Year and Date: 2007-10-18
• [Presentation] TMSC(MgBr)N2の特性を活かした多置換ピラゾール合成 (2007)
  • Author(s): 張功幸, 土田晋, 曽根良介, 青山豊彦
  • Organizer: 第53回日本薬学会東海支部大会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-07-07
• [Presentation] トリメチルシリルジアゾメタンとチオベンゾイルイソシアナート類の反応による2-アザアズレン類の新規合成 (2007)
  • Author(s): 森田幹雄, 張功幸, 青山豊彦
  • Organizer: 第37回複素環化学討論会
  • Place of Presentation: 長野