1-[(5R,8S,8aS)-5-propyloctahydroindolizine-8-yl]propan-1-one | 1162651-31-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚里西啶
• 英文名称: 1-[(5R,8S,8aS)-5-propyloctahydroindolizine-8-yl]propan-1-one
• 英文别名: 1-[(5R,8S,8aS)-5-propyl-1,2,3,5,6,7,8,8a-octahydroindolizin-8-yl]propan-1-one
• CAS: 1162651-31-1
• 化学式: C₁₄H₂₅NO
• 分子量: 223.359
• InChiKey: DQDOQMJFJYJSPV-AGIUHOORSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-[(5R,8S,8aS)-5-propyloctahydroindolizine-8-yl]propan-1-one 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以80%的产率得到(5R,8R,9S)-1-(5-propyloctahydroindolizin-8-yl)propan-1-one
  参考文献：
  名称：

  Formal Synthesis of (5R,8R,8aS)-Indolizidine 209I via Enaminones Incorporating Weinreb Amides

  摘要：

  A formal enantioselective synthesis of the amphibian alkaloid (5R,8R,8aS)-(-)-indolizidine 2091 (6) is reported. Control or the absolute, stereochemistry at C-5 resulted from application of the Davies procedure, which entails stereoselective conjugate addition of (R)-(+)-N-benzyl-1-phenylethylamine to tert-butyl (E)-hex-2-enoate. The resulting chiral adduct 26 was converted in eight steps into a pivotal enaminone incorporating a Weinreb amide, the inherent nucleophilicity of which was exploited in a cyclisation that yielded the key bicyclic intermediate (5R)-N-methoxy- N-methyl-5-propyl-1,2,3,5,6,7-hexahydroindolizine-8-carboxamide (38). Stereoselective catalytic hydrogenation of the alkene bond, reaction of the Weinreb amide with ethylmagnesium bromide, and epimerisation of the resulting ketone completed the formal synthesis of the target alkaloid.

  DOI：

  10.3987/com-08-s(d)68
• 作为产物：
  描述：

  (5R,8S,8aS)-N-methoxy-N-methyl-5-propyloctahydroindolizine-8-carboxamide 、 乙基溴化镁 在 盐酸 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以83%的产率得到1-[(5R,8S,8aS)-5-propyloctahydroindolizine-8-yl]propan-1-one
  参考文献：
  名称：

  Formal Synthesis of (5R,8R,8aS)-Indolizidine 209I via Enaminones Incorporating Weinreb Amides

  摘要：

  A formal enantioselective synthesis of the amphibian alkaloid (5R,8R,8aS)-(-)-indolizidine 2091 (6) is reported. Control or the absolute, stereochemistry at C-5 resulted from application of the Davies procedure, which entails stereoselective conjugate addition of (R)-(+)-N-benzyl-1-phenylethylamine to tert-butyl (E)-hex-2-enoate. The resulting chiral adduct 26 was converted in eight steps into a pivotal enaminone incorporating a Weinreb amide, the inherent nucleophilicity of which was exploited in a cyclisation that yielded the key bicyclic intermediate (5R)-N-methoxy- N-methyl-5-propyl-1,2,3,5,6,7-hexahydroindolizine-8-carboxamide (38). Stereoselective catalytic hydrogenation of the alkene bond, reaction of the Weinreb amide with ethylmagnesium bromide, and epimerisation of the resulting ketone completed the formal synthesis of the target alkaloid.

  DOI：

  10.3987/com-08-s(d)68

文献信息

• Formal Synthesis of (5R,8R,8aS)-Indolizidine 209I via Enaminones Incorporating Weinreb Amides
  作者：Joseph P. Michael、Charles B. de Koning、Darren L. Riley

  DOI：10.3987/com-08-s(d)68

  日期：——

  A formal enantioselective synthesis of the amphibian alkaloid (5R,8R,8aS)-(-)-indolizidine 2091 (6) is reported. Control or the absolute, stereochemistry at C-5 resulted from application of the Davies procedure, which entails stereoselective conjugate addition of (R)-(+)-N-benzyl-1-phenylethylamine to tert-butyl (E)-hex-2-enoate. The resulting chiral adduct 26 was converted in eight steps into a pivotal enaminone incorporating a Weinreb amide, the inherent nucleophilicity of which was exploited in a cyclisation that yielded the key bicyclic intermediate (5R)-N-methoxy- N-methyl-5-propyl-1,2,3,5,6,7-hexahydroindolizine-8-carboxamide (38). Stereoselective catalytic hydrogenation of the alkene bond, reaction of the Weinreb amide with ethylmagnesium bromide, and epimerisation of the resulting ketone completed the formal synthesis of the target alkaloid.