(-)-(S)-<3-Ethyl-4-oxo-2,3,4,9-tetrahydro-1H-carbazol-3-yl>propanoic acid methyl ester | 156408-04-7

• 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: (-)-(S)-<3-Ethyl-4-oxo-2,3,4,9-tetrahydro-1H-carbazol-3-yl>propanoic acid methyl ester
• 英文别名: methyl (S)-[3-ethyl-4-oxo-2,3,4,9-tetrahydro-1H-carbazol-3-yl]propanoate；methyl 3-[(3S)-3-ethyl-4-oxo-2,9-dihydro-1H-carbazol-3-yl]propanoate
• CAS: 156408-04-7
• 化学式: C₁₈H₂₁NO₃
• 分子量: 299.37
• InChiKey: UZIVRGSUAPQMPC-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-(S)-<3-Ethyl-4-oxo-2,3,4,9-tetrahydro-1H-carbazol-3-yl>propanoic acid methyl ester 在 4-二甲氨基吡啶 、 sodium hydroxide 、 sodium tetrahydroborate 、 sodium azide 、 双氧水 、 四丁基硫酸氢铵 、 三乙基硼氢化锂 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.5h， 生成 (3R)-3-(3-aminopropyl)-3-ethyl-9-(4-methoxyphenyl)sulfonyl-2,4-dihydro-1H-carbazol-4-ol
  参考文献：
  名称：

  Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael Reaction Using Chiral Imines: Enantioselective Synthesis of (+)-Aspidospermidine

  摘要：

  An enantioselective synthesis of (+)-aspidospermidine (1b) has been developed. The key strategic element was the stereocontrolled elaboration of quaternary carbon centers through the asymmetric Michael reaction, using chiral imines under neutral conditions. Thus, addition of imine 21, prepared from 2-ethylcyclohexanone and (R)-1-phenylethylamine, to methyl acrylate, led to cyclohexanone (S)-20 with 90% stereoselectivity (Scheme 3). The latter compound was then converted in six steps into dione 19 (Chart 6). Synthesis of [ABC]-type tricyclic carbazolone 18 was next accomplished, starting from this dione, by using the indole synthesis protocol developed by Suzuki. Critical to the success of this approach was the evolution, after extensive experimentation, of an efficient sequence for assembling D ring to carbazolone 18, having controlled during the events the ''natural'', cis CD ring junction. Thus, treatment of alcohol 57 with trifluoroacetic acid led to tetracycle 58 obtained as a single isomer with 94% yield (Chart 10). The intramolecular capture of a putative intermediary iminium ion, as illustrated in 52, by the carbamate nitrogen atom of 57 has been evoked to rationalize the observed stereoselectivity. The strategy we have adopted for the construction of the fifth E ring of 1b was in fact the methodology proposed by Magnus, based on an intramolecular Pummerer rearrangement (17 --> 59). Thus, synthesis of (+)-aspidospermidine (1b) has been achieved by a linear sequence of 22 chemical operations, starting with 2-ethylcyclohexanone, with an overall yield of 2.7%.

  DOI：

  10.1021/jo00088a008
• 作为产物：
  描述：

  (+)-(R)-1-Ethyl-2-oxo-4-(phenylthio)-3-cyclohexene-1-propanoic acid methyl ester 在 盐酸 、 copper(l) iodide 、 sodium methylate 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 、 甲苯 为溶剂， 反应 12.0h， 生成 (-)-(S)-<3-Ethyl-4-oxo-2,3,4,9-tetrahydro-1H-carbazol-3-yl>propanoic acid methyl ester
  参考文献：
  名称：

  Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael Reaction Using Chiral Imines: Enantioselective Synthesis of (+)-Aspidospermidine

  摘要：

  An enantioselective synthesis of (+)-aspidospermidine (1b) has been developed. The key strategic element was the stereocontrolled elaboration of quaternary carbon centers through the asymmetric Michael reaction, using chiral imines under neutral conditions. Thus, addition of imine 21, prepared from 2-ethylcyclohexanone and (R)-1-phenylethylamine, to methyl acrylate, led to cyclohexanone (S)-20 with 90% stereoselectivity (Scheme 3). The latter compound was then converted in six steps into dione 19 (Chart 6). Synthesis of [ABC]-type tricyclic carbazolone 18 was next accomplished, starting from this dione, by using the indole synthesis protocol developed by Suzuki. Critical to the success of this approach was the evolution, after extensive experimentation, of an efficient sequence for assembling D ring to carbazolone 18, having controlled during the events the ''natural'', cis CD ring junction. Thus, treatment of alcohol 57 with trifluoroacetic acid led to tetracycle 58 obtained as a single isomer with 94% yield (Chart 10). The intramolecular capture of a putative intermediary iminium ion, as illustrated in 52, by the carbamate nitrogen atom of 57 has been evoked to rationalize the observed stereoselectivity. The strategy we have adopted for the construction of the fifth E ring of 1b was in fact the methodology proposed by Magnus, based on an intramolecular Pummerer rearrangement (17 --> 59). Thus, synthesis of (+)-aspidospermidine (1b) has been achieved by a linear sequence of 22 chemical operations, starting with 2-ethylcyclohexanone, with an overall yield of 2.7%.

  DOI：

  10.1021/jo00088a008

文献信息

• Palladium-catalyzed syntheses of tetrahydrocarbazolones as advanced intermediates to carbazole alkaloids
  作者：Tricia L. Scott、Xiaomei Yu、Sobha P. Gorugantula、Grissell Carrero-Martínez、Björn C.G. Söderberg

  DOI：10.1016/j.tet.2006.08.100

  日期：2006.11

  Two sequential palladium-catalyzed reactions, an intermolecular Stille cross-coupling followed by a recently developed palladium-catalyzed reductive N-heteroannulation, have been employed as the key synthetic steps toward six tetrahydrocarbazolones. The products are advanced intermediates toward a number of naturally occurring carbazole alkaloids. (c) 2006 Elsevier Ltd. All rights reserved.