3-Methyl-2,3,5,6-tetrahydro-7(1H)-indolizinone | 141346-16-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-Methyl-2,3,5,6-tetrahydro-7(1H)-indolizinone
• 英文别名: 3-methyl-2,3,5,6-tetrahydro-1H-indolizin-7-one
• CAS: 141346-16-9
• 化学式: C₉H₁₃NO
• 分子量: 151.208
• InChiKey: UEUHCIQTMGBNHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  3-Methyl-2,3,5,6-tetrahydro-7(1H)-indolizinone 在 镍 氢气 、 硼酸 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 水 、 乙酸乙酯 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 5.0h， 生成 ((Z)-4-Hydroxy-7-methyl-3-phenyl-7,8,9,10-tetrahydro-6H-1-oxa-2,8-diaza-cyclopentacyclononen-5-yl)-phenyl-methanone
  参考文献：
  名称：

  Occhiato, Ernesto G.; Guarna, Antonio; Sarlo, Francesco de, Gazzetta Chimica Italiana, 1993, vol. 123, # 8, p. 425 - 430

  摘要：

  DOI：
• 作为产物：
  描述：

  2-Chloro-5-nitropentane 在 potassium carbonate 、 异氰酸苯酯 、 三乙胺 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 63.5h， 生成 3-Methyl-2,3,5,6-tetrahydro-7(1H)-indolizinone
  参考文献：
  名称：

  N-Bridgehead polycyclic compounds by sequential rearrangement-annulation of isoxazoline-5-spirocyclopropanes. 6. A general synthetic method for 5,6-dihydro-7(8H)- and 2,3,5,6-tetrahydro-7(1H)-indolizinones

  摘要：

  The thermal rearrangement-annulation of isoxazoline-5-spirocyclopropanes 4a-e substituted with a chain bearing a carbonyl group affords, in one step, 5,6-dihydro-7(8H)-indolizinones 5a-e. The rearrangement-annulation of isoxazoline-5-spirocyclopropanes 4f-h substituted with a chlorine on the side chain affords, also in one step, 2,3,5,6-tetrahydro-7(1H)-indolizinones 5f-h. When the cyclopropane ring is fused to a cyclohexane, or when a cyclohexanone is present in the side chain of isoxazoline 4, the process leads to N-bridgehead tricyclic compounds. Short rection times, mild reaction conditions, complete regioselectivity, and good stereoselectivity are the valuable features of this strategy.

  DOI：

  10.1021/jo00041a027

文献信息

• Enantioselective synthesis of indolizine derivatives by rearrangement-cyclization of isoxazoline-5-spirocyclopropanes
  作者：Ernesto G. Occhiato、Antonio Guarna、Laura Michela Spinetti

  DOI：10.1016/s0040-4020(01)81553-2

  日期：1993.1

  (3S,7S,8aS)-3-Methyl-7-hydroxyoctahydroindolizine (13) was prepared with an enantiomeric excess of 74%. in five steps starting from enantiomerically pure (S)-(+)-5-nitro-2-pentanol (5). (3S,5S,7S,8aS)-(-)-3-Methyl-5-phenyl-7-hydroxyoctahydroindolizine (15) and (3S,5R,7R,8aR)-(+)-3-methyl-5-phenyl-7-hydroxyoctahydroindolizine (16) were also obtained starting from (5) with an ee of 96%. The synthetic strategy required the enantioselective enzymatic reduction of 5-nitro-2-pentanone (4) to 5 (> 99% ee) and its conversion to (R)-(-)-2-chloro-5-nitropentane (7) (> 90% ee). Cycloadditions of the corresponding nitrile oxide prepared in situ from 7 with methylenecyclopropane (8) or 1-methylene-2-phenylcyclopropane (9) produced chiral isoxazolines 1 and 2, which were converted by thermolysis to 2,3,5,6-tetrahydro-3-methylindolizin-7(1H)-one (10), and 2,3,5,6-tetrahydro-3-methyl-5-phenylindolizin-7(1H)-ones (11) and (12) respectively. The enantioselectivity of the thermal rearrangement is dependent on the experimental conditions and on the structures of the chiral isoxazolines. Catalytic hydrogenation of the indolizinones 10, 11 and 12, afforded the substituted hydroxyoctahydroindolizines 13, 15 and 16 with high stereoselective control of all stereogenic centers.

  (3S,7S,8aS)-3-甲基-7-羟基八氢吲哚嗪（13）以(3S,7S,8aS)-3-甲基-7-羟基八氢吲哚嗪的形式制备，其对映体过量为74%，从旋光纯的(S)-(+)-5-硝基-2-戊醇（5）开始，通过五步反应合成。同样地，从(5)开始，还获得了(3S,5S,7S,8aS)-(-)-3-甲基-5-苯基-7-羟基八氢吲哚嗪（15）和(3S,5R,7R,8aR)-(+)-3-甲基-5-苯基-7-羟基八氢吲哚嗪（16），其ee为96%。合成策略需要5-硝基-2-戊酮（4）通过酶促不对称还原生成(5)（> 99% ee），随后将其转化为(R)-(-)-2-氯-5-硝基戊烷（7）（> 90% ee）。将7原位制备的腈亚胺与甲基环丙烷（8）或1-甲基-2-苯基环丙烷（9）进行环加成，产生手性异恶唑烷1和2，随后通过热裂解分别转化为2,3,5,6-四氢-3-甲基吲哚嗪-7(1H)-酮（10）、2,3,5,6-四氢-3-甲基-5-苯基吲哚嗪-7(1H)-酮（11）和（12）。热重排的对映选择性取决于实验条件和手性异恶唑烷的结构。催化氢化吲哚嗪酮10、11和12，得到取代的羟基八氢吲哚嗪13、15和16，对所有手性中心均具有高度的立体选择性控制。
• N-Bridgehead polycyclic compounds by sequential rearrangement-annulation of isoxazoline-5-spirocyclopropanes. 6. A general synthetic method for 5,6-dihydro-7(8H)- and 2,3,5,6-tetrahydro-7(1H)-indolizinones
  作者：Ernesto G. Occhiato、Antonio Guarna、Alberto Brandi、Andrea Goti、Francesco De Sarlo

  DOI：10.1021/jo00041a027

  日期：1992.7

  The thermal rearrangement-annulation of isoxazoline-5-spirocyclopropanes 4a-e substituted with a chain bearing a carbonyl group affords, in one step, 5,6-dihydro-7(8H)-indolizinones 5a-e. The rearrangement-annulation of isoxazoline-5-spirocyclopropanes 4f-h substituted with a chlorine on the side chain affords, also in one step, 2,3,5,6-tetrahydro-7(1H)-indolizinones 5f-h. When the cyclopropane ring is fused to a cyclohexane, or when a cyclohexanone is present in the side chain of isoxazoline 4, the process leads to N-bridgehead tricyclic compounds. Short rection times, mild reaction conditions, complete regioselectivity, and good stereoselectivity are the valuable features of this strategy.
• Occhiato, Ernesto G.; Guarna, Antonio; Sarlo, Francesco de, Gazzetta Chimica Italiana, 1993, vol. 123, # 8, p. 425 - 430
  作者：Occhiato, Ernesto G.、Guarna, Antonio、Sarlo, Francesco de、Brandi, Alberto、Goti, Andrea、et al.

  DOI：——

  日期：——

表征谱图