3-(3-Ethyl-2-hydroxy-tetrahydro-furan-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]propionamide | 195246-29-8

• 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: 3-(3-Ethyl-2-hydroxy-tetrahydro-furan-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]propionamide
• 英文别名: 3-[(3S)-3-ethyl-2-hydroxyoxolan-3-yl]-N-[2-(1H-indol-3-yl)ethyl]propanamide
• CAS: 195246-29-8
• 化学式: C₁₉H₂₆N₂O₃
• 分子量: 330.427
• InChiKey: HHTKNCIUQQUHGZ-GGYWPGCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  74.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-Ethyl-2-hydroxy-tetrahydro-furan-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]propionamide 在 sodium hydroxide 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 反应 48.5h， 生成 (1S,12bR)-1-ethyl-1-(2-hydroxyethyl)-4-oxo-2,3,6,7,12,12b-hexahydro-1H-indolo[2,3-a]quinolizine
  参考文献：
  名称：

  Desymmetrization of Benzoic Acid in the Context of the Asymmetric Birch Reduction−Alkylation Protocol. Asymmetric Total Syntheses of (−)-Eburnamonine and (−)-Aspidospermidine

  摘要：

  The highly diastereoselective potassium in ammonia reduction-ethylation (EtI) of the chiral 2-(trimethylsilyl)benzamide 1b to give 1,4-cyclohexadiene 3 is the key step in asymmetric syntheses of (-)-eburnamonine (4) and (-)-aspidospermidine (5). Cyclohexadiene 3 was converted to cyclohexanone 7, which provided the trimethylsilyl-substituted butyrolactone 9 utilized for the synthesis of 4 and butyrolactone 13 required for the synthesis of 5. The preparation of 9 depended upon the completely regioselective silicon-directed Baeyer-Villiger oxidation 7-->8; Baeyer-Villiger oxidation of the cyclohexenone 10 also was regioselective to give the desired enol lactone 11 in 92% yield. Remarkable diastereoselectivity was observed for the kinetically controlled cyclization of the acyl imminium ion derived from the vinyl-substituted carboxaldehyde 16b; treatment of 16b with 5 equiv of CF3CO2H in CH2Cl2 at -55 degrees C gave an 18:1 mixture of 17 and its C(3) beta-epimer in 93% yield. The oxidation of alcohol 18 containing sensitive indole and piperidine rings was best carried out with tetrapropylammonium perruthenate/N-methylmorpholine N-oxide to give (-)-eburnamonine (4) in 97% yield. The asymmetric synthesis of (-)-aspidospermidine 5 involved the conversion of butyrolactone 13 to the hydroxylactam 22, the Harley-Mason cyclization of 22 to 23, and reduction of 23 with LiAlH4.

  DOI：

  10.1021/jo9707592
• 作为产物：
  描述：

  (4R)-4-ethyl-4-[(2S)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-3-trimethylsilylcyclohexan-1-one 在 Rh on carbon disodium hydrogenphosphate 、 叠氮磷酸二苯酯 、 氢气 、 二异丁基氢化铝 、 对甲苯磺酸 、 三乙胺 、 三氟乙酸酐 、 copper dichloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 51.75h， 生成 3-(3-Ethyl-2-hydroxy-tetrahydro-furan-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]propionamide
  参考文献：
  名称：

  Desymmetrization of Benzoic Acid in the Context of the Asymmetric Birch Reduction−Alkylation Protocol. Asymmetric Total Syntheses of (−)-Eburnamonine and (−)-Aspidospermidine

  摘要：

  The highly diastereoselective potassium in ammonia reduction-ethylation (EtI) of the chiral 2-(trimethylsilyl)benzamide 1b to give 1,4-cyclohexadiene 3 is the key step in asymmetric syntheses of (-)-eburnamonine (4) and (-)-aspidospermidine (5). Cyclohexadiene 3 was converted to cyclohexanone 7, which provided the trimethylsilyl-substituted butyrolactone 9 utilized for the synthesis of 4 and butyrolactone 13 required for the synthesis of 5. The preparation of 9 depended upon the completely regioselective silicon-directed Baeyer-Villiger oxidation 7-->8; Baeyer-Villiger oxidation of the cyclohexenone 10 also was regioselective to give the desired enol lactone 11 in 92% yield. Remarkable diastereoselectivity was observed for the kinetically controlled cyclization of the acyl imminium ion derived from the vinyl-substituted carboxaldehyde 16b; treatment of 16b with 5 equiv of CF3CO2H in CH2Cl2 at -55 degrees C gave an 18:1 mixture of 17 and its C(3) beta-epimer in 93% yield. The oxidation of alcohol 18 containing sensitive indole and piperidine rings was best carried out with tetrapropylammonium perruthenate/N-methylmorpholine N-oxide to give (-)-eburnamonine (4) in 97% yield. The asymmetric synthesis of (-)-aspidospermidine 5 involved the conversion of butyrolactone 13 to the hydroxylactam 22, the Harley-Mason cyclization of 22 to 23, and reduction of 23 with LiAlH4.

  DOI：

  10.1021/jo9707592

文献信息

• Asymmetric Construction of Quaternary Carbon Centers by Sequential Conjugate Addition of Lithium Amide and in Situ Alkylation: Utility in the Synthesis of (−)-Aspidospermidine
  作者：Mayuko Suzuki、Yoshito Kawamoto、Takeo Sakai、Yasutomo Yamamoto、Kiyoshi Tomioka

  DOI：10.1021/ol802759j

  日期：2009.2.5

  subsequent in situ alkylation gave a chiral cyclopentane derivative bearing a quaternary carbon with high enantio- and diastereoselectivity. The cyclopentane derivative was converted successfully to (−)-aspidospermidine.

  手性二醚配体控制的氨基锂向环戊烯羧酸酯的不对称共轭加成以及随后的原位烷基化得到具有高对映体和非对映体选择性的带有季碳的手性环戊烷衍生物。环戊烷衍生物成功转化为（-）-aspidospermidine。