2-(1-Benzoyl-4-vinyl-2,3-dihydro-1H-indol-3-yl)-1-imidazol-1-yl-ethanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-(1-Benzoyl-4-vinyl-2,3-dihydro-1H-indol-3-yl)-1-imidazol-1-yl-ethanone
• 英文别名: 2-(1-Benzoyl-4-ethenyl-2,3-dihydroindol-3-yl)-1-imidazol-1-ylethanone
• 化学式: C₂₂H₁₉N₃O₂
• 分子量: 357.412
• InChiKey: BPKNXWRQQPQUHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1-Benzoyl-4-vinyl-2,3-dihydro-1H-indol-3-yl)-1-imidazol-1-yl-ethanone 、 甲胺 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 2-(1-Benzoyl-4-vinyl-2,3-dihydro-1H-indol-3-yl)-N-methylacetamide
  参考文献：
  名称：

  An Approach to Lysergic Acid Utilizing an Intramolecular Isomuenchnone Cycloaddition Pathway

  摘要：

  A series of alkenyl- and alkynyl-substituted diazo imides were prepared to demonstrate that the intramolecular cycloaddition across a transient isomunchnone dipole was a viable approach to the quinoline ring system (rings C and D) of the ergot alkaloids. The diazo imides were synthesized by N-malonylacylation of the appropriate amide followed by exposure to standard diazo transfer conditions. The carbenoid intermediate derived by treatment of the diazo imide with rhodium(II) acetate undergoes ready cyclization onto the neighboring amide carbonyl oxygen to generate an isomunchnone intermediate. Subsequent 1,3-dipolar cycloaddition across the pendant olefin affords the cycloadduct in high yield. The stereochemical assignment of several of the cycloadducts was deduced by X-ray crystallography. The stereochemical outcome of the reaction is the consequence of an endo cycloaddition of the neighboring pi-bond across the transient isomunchnone dipole. Exposure of the olefinic cycloadduct to boron trifluoride etherate resulted in exclusive carbon-oxygen bond cleavage producing a transient N-acyliminium ion which undergoes rapid proton loss to afford an enamide derivative. In contrast, exposure of the acetylenic cycloadduct to boron trifluoride etherate resulted in exclusive carbon-nitrogen bond cleavage. The resulting oxonium ion underwent reduction with triethylsilane, producing a dihydrofuran derivative. In the absence of a reducing agent, the alkyne cycloadduct underwent a retro Diels-Alder reaction to give a substituted furan derivative in high yield. The Rh(II) acetate catalyzed reaction of the appropriate diazo imide precursor to lysergic acid resulted in a mixture of the desired dipolar cycloadduct as well as a C-H insertion product. Switching to rhodium(II) perfluorobutyrate as the catalyst significantly enhanced the cycloadditon pathway. The inability to carry out a double-bond isomerization thwarted our efforts to synthesize lysergic acid.

  DOI：

  10.1021/jo00114a017
• 作为产物：
  描述：

  N,N'-羰基二咪唑 、 (1-Benzoyl-4-vinyl-2,3-dihydro-1H-indol-3-yl)-acetic acid 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 2-(1-Benzoyl-4-vinyl-2,3-dihydro-1H-indol-3-yl)-1-imidazol-1-yl-ethanone
  参考文献：
  名称：

  An Approach to Lysergic Acid Utilizing an Intramolecular Isomuenchnone Cycloaddition Pathway

  摘要：

  A series of alkenyl- and alkynyl-substituted diazo imides were prepared to demonstrate that the intramolecular cycloaddition across a transient isomunchnone dipole was a viable approach to the quinoline ring system (rings C and D) of the ergot alkaloids. The diazo imides were synthesized by N-malonylacylation of the appropriate amide followed by exposure to standard diazo transfer conditions. The carbenoid intermediate derived by treatment of the diazo imide with rhodium(II) acetate undergoes ready cyclization onto the neighboring amide carbonyl oxygen to generate an isomunchnone intermediate. Subsequent 1,3-dipolar cycloaddition across the pendant olefin affords the cycloadduct in high yield. The stereochemical assignment of several of the cycloadducts was deduced by X-ray crystallography. The stereochemical outcome of the reaction is the consequence of an endo cycloaddition of the neighboring pi-bond across the transient isomunchnone dipole. Exposure of the olefinic cycloadduct to boron trifluoride etherate resulted in exclusive carbon-oxygen bond cleavage producing a transient N-acyliminium ion which undergoes rapid proton loss to afford an enamide derivative. In contrast, exposure of the acetylenic cycloadduct to boron trifluoride etherate resulted in exclusive carbon-nitrogen bond cleavage. The resulting oxonium ion underwent reduction with triethylsilane, producing a dihydrofuran derivative. In the absence of a reducing agent, the alkyne cycloadduct underwent a retro Diels-Alder reaction to give a substituted furan derivative in high yield. The Rh(II) acetate catalyzed reaction of the appropriate diazo imide precursor to lysergic acid resulted in a mixture of the desired dipolar cycloadduct as well as a C-H insertion product. Switching to rhodium(II) perfluorobutyrate as the catalyst significantly enhanced the cycloadditon pathway. The inability to carry out a double-bond isomerization thwarted our efforts to synthesize lysergic acid.

  DOI：

  10.1021/jo00114a017

文献信息

• An Approach to Lysergic Acid Utilizing an Intramolecular Isomuenchnone Cycloaddition Pathway
  作者：Joseph P. Marino、Martin H. Osterhout、Albert Padwa

  DOI：10.1021/jo00114a017

  日期：1995.5

  A series of alkenyl- and alkynyl-substituted diazo imides were prepared to demonstrate that the intramolecular cycloaddition across a transient isomunchnone dipole was a viable approach to the quinoline ring system (rings C and D) of the ergot alkaloids. The diazo imides were synthesized by N-malonylacylation of the appropriate amide followed by exposure to standard diazo transfer conditions. The carbenoid intermediate derived by treatment of the diazo imide with rhodium(II) acetate undergoes ready cyclization onto the neighboring amide carbonyl oxygen to generate an isomunchnone intermediate. Subsequent 1,3-dipolar cycloaddition across the pendant olefin affords the cycloadduct in high yield. The stereochemical assignment of several of the cycloadducts was deduced by X-ray crystallography. The stereochemical outcome of the reaction is the consequence of an endo cycloaddition of the neighboring pi-bond across the transient isomunchnone dipole. Exposure of the olefinic cycloadduct to boron trifluoride etherate resulted in exclusive carbon-oxygen bond cleavage producing a transient N-acyliminium ion which undergoes rapid proton loss to afford an enamide derivative. In contrast, exposure of the acetylenic cycloadduct to boron trifluoride etherate resulted in exclusive carbon-nitrogen bond cleavage. The resulting oxonium ion underwent reduction with triethylsilane, producing a dihydrofuran derivative. In the absence of a reducing agent, the alkyne cycloadduct underwent a retro Diels-Alder reaction to give a substituted furan derivative in high yield. The Rh(II) acetate catalyzed reaction of the appropriate diazo imide precursor to lysergic acid resulted in a mixture of the desired dipolar cycloadduct as well as a C-H insertion product. Switching to rhodium(II) perfluorobutyrate as the catalyst significantly enhanced the cycloadditon pathway. The inability to carry out a double-bond isomerization thwarted our efforts to synthesize lysergic acid.