2-(1-Benzoyl-4-vinyl-2,3-dihydro-1H-indol-3-yl)-N-methylacetamide | 163810-66-0

• 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)-N-methylacetamide
• 英文别名: 2-(1-benzoyl-4-ethenyl-2,3-dihydroindol-3-yl)-N-methylacetamide
• CAS: 163810-66-0
• 化学式: C₂₀H₂₀N₂O₂
• 分子量: 320.391
• InChiKey: UKIVOSQYIYVOQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(1-Benzoyl-4-vinyl-2,3-dihydro-1H-indol-3-yl)-N-methylacetamide 在 sodium periodate 作用下， 以 甲醇 、 水 、 苯 为溶剂， 反应 15.0h， 生成 N[(1-benzoyl-4-vinyl-2,3-dihydro-1H-indol-3-yl)acetyl]-2-(ethylsulfinyl)-N-methylacetamide
  参考文献：
  名称：

  使用亚氨基亚砜的Pummerer环化-去质子化-环加成级联反应进行生物碱合成。

  摘要：

  带有束缚的链烯基的亚氨基亚砜的Pummerer反应已用于几种生物碱的合成。通过将适当的酰胺与（乙基亚硫基）乙酰氯加热，然后将高碘酸钠氧化，可以轻松获得级联序列所需的亚氨基亚砜。通过用乙酸酐和对甲苯磺酸处理亚氨基亚砜而获得的最初形成的硫鎓离子与相邻的亚氨基基团反应，随后生成的氧鎓离子经历去质子化反应，生成异丁香酮偶极。该中离子甜菜碱中间体经过相邻的pi键易发生分子内偶极环加成反应。将所得的环加合物暴露于另外的乙酸酐中导致开环并形成5-乙酰氧基取代的2（1H）-吡啶酮。这种六环杂环系统构成了合成各种吡啶，喹喔啉和锁骨生物碱的有价值的组成部分。环化-去质子化-环加成级联反应已成功地应用于天然存在的生物碱on药碱，地西醌，（+/-）-羽扇豆碱，（+/-）-anagyrine，（+/-）-pumiliotoxin C和（ +/-）-肋骨

  DOI：

  10.1021/jo9915729
• 作为产物：
  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

文献信息

• Using the Pummerer Cyclization−Deprotonation−Cycloaddition Cascade of Imidosulfoxides for Alkaloid Synthesis
  作者：Albert Padwa、Todd M. Heidelbaugh、Jeffrey T. Kuethe

  DOI：10.1021/jo9915729

  日期：2000.4.1

  opening and formation of a 5-acetoxy-substituted 2(1H)-pyridone. This six-ring heterocyclic system constitutes a valuable building block for the synthesis of a variety of pyridine, quinolizidine, and clavine alkaloids. The cyclization-deprotonation-cycloaddition cascade has been successfully applied to the synthesis of the naturally occurring alkaloids onychnine, dielsiquinone, (+/-)-lupinine, (+/-)-anagyrine

  带有束缚的链烯基的亚氨基亚砜的Pummerer反应已用于几种生物碱的合成。通过将适当的酰胺与（乙基亚硫基）乙酰氯加热，然后将高碘酸钠氧化，可以轻松获得级联序列所需的亚氨基亚砜。通过用乙酸酐和对甲苯磺酸处理亚氨基亚砜而获得的最初形成的硫鎓离子与相邻的亚氨基基团反应，随后生成的氧鎓离子经历去质子化反应，生成异丁香酮偶极。该中离子甜菜碱中间体经过相邻的pi键易发生分子内偶极环加成反应。将所得的环加合物暴露于另外的乙酸酐中导致开环并形成5-乙酰氧基取代的2（1H）-吡啶酮。这种六环杂环系统构成了合成各种吡啶，喹喔啉和锁骨生物碱的有价值的组成部分。环化-去质子化-环加成级联反应已成功地应用于天然存在的生物碱on药碱，地西醌，（+/-）-羽扇豆碱，（+/-）-anagyrine，（+/-）-pumiliotoxin C和（ +/-）-肋骨
• 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.