3,4,6,7,12,12b-Hexahydro-1H-indolo[2,3-a]quinolizin-2-one | 1217-82-9

• 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: 3,4,6,7,12,12b-Hexahydro-1H-indolo[2,3-a]quinolizin-2-one
• 英文别名: 3,4,6,7,12,12b-hexahydroindolo<2,3-a>quinolizin-2(1H)-one；1,2,3,4,6,7,12,12b-octahydroindolo<2,3-a>quinolizin-2-one；2-Oxo-1,2,3,4,6,7,12,12b-octahydroindolo<2,3-a>chinolizin
• CAS: 1217-82-9；55854-97-2
• 化学式: C₁₅H₁₆N₂O
• 分子量: 240.305
• InChiKey: NVDIWIVBXVVMIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  36.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4,6,7,12,12b-Hexahydro-1H-indolo[2,3-a]quinolizin-2-one 在 盐酸 、 4-二甲氨基吡啶 、 1,4-diazabicyclo[5.4.0]-7-undecene 、 次氯酸叔丁酯 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.17h， 生成 dimethyl 17-oxo-3,14,15,16-tetradehydroyohimban-1,16-dicarboxylate
  参考文献：
  名称：

  Total syntheses of yohimbe alkaloids, with stereoselection for the normal, allo, and 3-epiallo series, based on annelations of 4-methoxy-1,2-dihydropyridones

  摘要：

  N-[2-(1H-3-indolyl)ethyl]-2,3-dihydro-4-pyridone (31) was generated in two steps (77% yield) from tryptamine and N-methyl-4-piperidone methiodide. Its cyclization (90% yield) and oxidation (91% yield) provided the tetracyclic analogue 32. O-Methylation and Robinson-type annelation of these vinylogous lactams (the latter in form of its N(a)-carbamate) furnished the dienones 38 (64%) and 43 (90%). Further elaboration by cyclization and/or reduction reactions selectively provided the 15,16-didehydroyohimbinones 7 or 44. Their reductions then led to yohimbinone (52, 20% overall yield from tryptamine), alloyohimbinone (11, 19% overall yield), and 3-epi-alloyohimbinone (10, 23% overall yield), which led to yohimbine (3), beta-yohimbine (9), 3-epi-alloyohimbine (53), and 3-epi-17-epi-alloyohimbine (54).

  DOI：

  10.1021/jo00008a025
• 作为产物：
  描述：

  2',3',5',6',8',8a'-hexahydrodispiro[indole-3,1'-indolizine-7',2''-[1,3]dioxolane] 在 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 15.5h， 生成 3,4,6,7,12,12b-Hexahydro-1H-indolo[2,3-a]quinolizin-2-one
  参考文献：
  名称：

  Synthetic applications of protected 2-aryl-4-piperidones. 7. Synthesis of 1-ethylindolo[2,3-a]quinolizidin-2-one

  摘要：

  The synthesis of 1-ethylindolo[2,3-a]quinolizidin-2-one (1) by the intramolecular cyclization of protected N-(2-hydroxyethyl)-2-[1-(phenylsulfonyl)-3-indolyl]-4-piperidone 15 by the action of K(t)BuO and further acid treatment is reported. The methodology has been first carried out for its deethyl analogue 2 from (hydroxyethyl)piperidine 14 and has shown to be a good general method to reach indolo[2,3-a]quinolizidin-2-one systems. Compound 1 has also been obtained by an unusual rearrangement in acidic medium of 7-ethylhexahydropyrido[1',2':1,2]pyrazino[4,3-a]indole.

  DOI：

  10.1021/jo00022a015

文献信息

• Access to Electron-Rich Arene-Fused Hexahydroquinolizinones through a Gold-Catalysis-Initiated Cascade Process
  作者：Lianzhu Liu、Liming Zhang

  DOI：10.1002/anie.201203303

  日期：2012.7.16

  Golden Cascade: With a tethered, electron‐rich arene as the internal nucleophile, a gold‐catalyzed amide cyclization to an alkyne initiates a cascade process that ends with a Ferrier rearrangement. Electron‐rich arene‐bearing hexahydroquinolizin‐2‐ones are formed in good yields and can be converted into indole alkaloids in only a few steps.

  黄金级联：以束缚的、富电子的芳烃作为内部亲核试剂，金催化的酰胺环化成炔引发级联过程，以费里尔重排结束。富含电子的芳烃六氢喹啉-2-酮以良好的产率形成，只需几步即可转化为吲哚生物碱。
• A new route to heterocyclic compounds by the mercuric acetate oxidation of N-alkyl substituted 4-piperidones
  作者：Andrew C. Flick、Albert Padwa

  DOI：10.1016/j.tetlet.2008.07.109

  日期：2008.9

  N-Alkyl substituted 4-piperidones readily undergo oxidation in high yield upon reaction with mercuric acetate. Application of the oxidation to the synthesis of the skeletal framework of several alkaloids is described.

  N-烷基取代的4-哌啶酮在与乙酸汞反应后容易以高收率进行氧化。描述了将氧化应用于几种生物碱的骨架构架的合成。
• Synthesis of Reserpine-type Alkaloids, I. An Approach to the Preparation of Tetracyclic Key Intermediates
  作者：Csaba Szántay、Katalin Honty、László Tőke、GáBor Blaskó、Eszter Baitz-Gács

  DOI：10.1002/jlac.198319830802

  日期：1983.8.15

  Key intermediates of type 2 serving the synthesis of reserpine-type alkaloids were prepared in different routes.

  以不同的途径制备了用于合成利血平型生物碱的2型关键中间体。
• A general synthesis of aryl[2,3-a]quinolizin-2-ones
  作者：J.P. Vacca

  DOI：10.1016/s0040-4039(00)94869-x

  日期：1985.1

  A convenient and general synthesis of arylquinolizines utilizing a hetero Diels-Alder reaction is described.

  描述了利用杂Diels-Alder反应方便且通用的芳基喹唑啉合成。
• Short Synthesis of 2-oxo-1,2,3,4,6,7,12,12b-Octahydroindolo[2,3-<i>a</i>]quinolizine
  作者：Laurence W. Reilly、Randall B. Nelson,、Gordon W. Gribble

  DOI：10.1080/00304948.2018.1525985

  日期：2018.9.3

  prepared by several groups, and Kametani parlayed 1 into a synthesis of yohimbine. In connection with a project in our laboratory we required a short, efficient, and atom-economical preparation of 1. Of the several known syntheses of 1 only the method of Potts and Nasri seemed suitable for us. We now describe a modification of this synthesis that involves the coupling of 3-acetylindole (2) and 4-methoxypyridine

  标题化合物 2-oxo-1,2,3,4,6,7,12,12b-Octahydroindolo[2,3-a]quinolizine (1) 于 1952 年由 Groves 和 Swan 作为切入点首次合成育亨宾 - 利血平 - 红木碱家族的生物碱。随后，这种吲哚酮由几个小组制备，龟谷将 1 合成了育亨宾。在我们实验室的一个项目中，我们需要 1 的简短、高效和原子经济的制备。在 1 的几种已知合成中，只有 Potts 和 Nasri 的方法似乎适合我们。我们现在描述了这种合成的改进，包括 3-乙酰吲哚 (2) 和 4-甲氧基吡啶 (3) 的偶联（方案 1）。