3-((2-indol-1-yl)ethyl)piperidin-2-one | 159682-71-0

• 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-((2-indol-1-yl)ethyl)piperidin-2-one
• 英文别名: 3-(2-(Indol-1-yl)ethyl)piperidin-2-one；3-(2-indol-1-yl)ethylpiperidine-2-one；3-(2-indol-1-yl)ethylpiperidin-2-one；3-(2-indolylethyl)piperidin-2-one；3-(2-Indol-1-ylethyl)piperidin-2-one
• CAS: 159682-71-0
• 化学式: C₁₅H₁₈N₂O
• 分子量: 242.321
• InChiKey: XHLOBVLMYSZYDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  34
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-((2-indol-1-yl)ethyl)piperidin-2-one 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 0.75h， 以63%的产率得到3-(2-indol-1-yl)ethylpiperidine-2-thione
  参考文献：
  名称：

  Cycloaddition Chemistry of Anhydro-4-hydroxy-1,3-thiazolium Hydroxides (Thioisomünchnones) for the Synthesis of Heterocycles

  摘要：

  一系列的α,α-二取代硫代异肟酮通过在三乙胺存在下，用溴乙酰氯处理非环状或环状硫代酰胺来制备。结果发现，这些介离子偶极体会发生双分子1,3-偶极环加成反应与多种不同的偶极体分子。当硫代酰胺的α-位上有氢原子时，最初形成的N-酰基亚胺离子会快速失去质子，产生S,N-酮烯醇缩醛，比形成硫代异肟酮的速度更快。还研究了几种带有附加烯烃的取代硫代异肟酮的环加成行为。内向环加成反应是邻近的π键跨过瞬态硫代异肟酮偶极子的结果，这是分子内反应的立体化学产物的成因。分子力学计算表明，内向非对映异构体的能量比相应的向外构体显著更低。尝试将硫代异肟酮偶极子环加成到附加的吲哚环上未能成功。相反，高产率地形成通过吲哚环以亲核方式环化到硫代N-酰基亚胺离子上的产物。

  DOI：

  10.1055/s-1994-25621
• 作为产物：
  描述：

  N-<2-(toluenesulfonyl)oxyethyl>indole 在 正丁基锂 、 sodium iodide 作用下， 以 四氢呋喃 、 正己烷 、 丙酮 为溶剂， 反应 15.0h， 生成 3-((2-indol-1-yl)ethyl)piperidin-2-one
  参考文献：
  名称：

  Intramolecular Cycloaddition of Isomunchnone Dipoles to Heteroaromatic .pi.-Systems

  摘要：

  A series of furanyl-, thienyl-, and indole-substituted diazo imides were prepared by treating the appropriate amides with diketene to give the N-acetoacylated imides. Exposure of the imides to standard diazo transfer conditions afforded the desired diazo imides. Treatment of these diazo imides bearing tethered heterocyclic rings with rhodium(II) acetate affords transient isomunchnone dipoles. The mesoionic dipoles are formed by cyclization of the rhodium carbenoid onto the neighboring amide carbonyl oxygen atom. The scope and limitations of the intramolecular 1,3-dipolar cycloaddition of the isomunchnones across a tethered furan and thiophene ring were studied. The facility of the internal cycloaddition is influenced by the length and nature of the tether connecting the dipole and dipolarophile functionalities. The reaction is critically dependent on conformational factors in the transition state. In addition, the first examples of intramolecular cycloaddition of isomunchnones to indole dipolarophiles are reported. Cycloadditions of this type generate highly functionalized polyheterocyclic systems with complete relative stereocontrol at the newly formed stereocenters.

  DOI：

  10.1021/jo00102a037

文献信息

• Cycloaddition Chemistry of Anhydro-4-hydroxy-1,3-thiazolium Hydroxides (Thioisomünchnones) for the Synthesis of Heterocycles
  作者：Albert Padwa、Scott R. Harring、Donald L. Hertzog、William R. Nadler

  DOI：10.1055/s-1994-25621

  日期：——

  A series of α,α-disubstituted thioisomünchnones were prepared by treating acyclic or cyclic thioamides with bromoacetyl chloride in the presence of triethylamine. The resulting mesoionic dipole was found to undergo bimolecular 1,3-dipolar cycloaddition with several different dipolarophiles. When a hydrogen atom is present in the α-position of the thioamide, the initially formed N-acyl iminium ion undergoes proton loss to produce a S,N-ketene acetal at a faster rate than thioisomünchnone formation. The cycloaddition behavior of several substituted thioisomünchnones which possess a tethered alkene were also examined. The stereochemical outcome of the intramolecular reaction is the consequence of an endo cycloaddition of the neighboring π-bond across the transient thioisomünchnone dipole. Molecular mechanics calculations reveal that the endo diastereomers are significantly lower in energy than the corresponding exo isomers. Attempts to cycloadd the thioisomünchnone dipole across a tethered indolyl ring were unsuccessful. Instead, products derived by nucleophilic cyclization of the indolyl ring onto the thio N-acyl iminium ion were formed in good yield.

  一系列的α,α-二取代硫代异肟酮通过在三乙胺存在下，用溴乙酰氯处理非环状或环状硫代酰胺来制备。结果发现，这些介离子偶极体会发生双分子1,3-偶极环加成反应与多种不同的偶极体分子。当硫代酰胺的α-位上有氢原子时，最初形成的N-酰基亚胺离子会快速失去质子，产生S,N-酮烯醇缩醛，比形成硫代异肟酮的速度更快。还研究了几种带有附加烯烃的取代硫代异肟酮的环加成行为。内向环加成反应是邻近的π键跨过瞬态硫代异肟酮偶极子的结果，这是分子内反应的立体化学产物的成因。分子力学计算表明，内向非对映异构体的能量比相应的向外构体显著更低。尝试将硫代异肟酮偶极子环加成到附加的吲哚环上未能成功。相反，高产率地形成通过吲哚环以亲核方式环化到硫代N-酰基亚胺离子上的产物。
• Intramolecular Cycloaddition of Isomunchnone Dipoles to Heteroaromatic .pi.-Systems
  作者：Albert Padwa、Donald L. Hertzog、William R. Nadler

  DOI：10.1021/jo00102a037

  日期：1994.11

  A series of furanyl-, thienyl-, and indole-substituted diazo imides were prepared by treating the appropriate amides with diketene to give the N-acetoacylated imides. Exposure of the imides to standard diazo transfer conditions afforded the desired diazo imides. Treatment of these diazo imides bearing tethered heterocyclic rings with rhodium(II) acetate affords transient isomunchnone dipoles. The mesoionic dipoles are formed by cyclization of the rhodium carbenoid onto the neighboring amide carbonyl oxygen atom. The scope and limitations of the intramolecular 1,3-dipolar cycloaddition of the isomunchnones across a tethered furan and thiophene ring were studied. The facility of the internal cycloaddition is influenced by the length and nature of the tether connecting the dipole and dipolarophile functionalities. The reaction is critically dependent on conformational factors in the transition state. In addition, the first examples of intramolecular cycloaddition of isomunchnones to indole dipolarophiles are reported. Cycloadditions of this type generate highly functionalized polyheterocyclic systems with complete relative stereocontrol at the newly formed stereocenters.
• 8H-Anhydro-4-hydroxy-2-oxo-1,3-thiazinium Hydroxides as Mesoionic 1,4-Dipoles
  作者：Albert Padwa、Steven J. Coats、Lazaros Hadjarapoglou

  DOI：10.3987/com-93-s(b)16

  日期：——

  The previously unknown 8H-anhydro-4-hydroxy-2-oxo-1,3-thiazinium hydroxides (1) were prepared and their 1,4-dipolar cycloaddition behavior was examined. In most cases, elimination of the proton in the 8-position of the mesoionic ring was observed to occur unless extremely reactive dipolarophiles were used. The S,N-ketene acetals were converted to the corresponding alpha-diazo ketones for further study.
• A One-Pot Bicycloannulation Method for the Synthesis of Tetrahydroisoquinoline Systems
  作者：Albert Padwa、L. Scott Beall、Todd M. Heidelbaugh、Bing Liu、Scott M. Sheehan

  DOI：10.1021/jo991742h

  日期：2000.5.1

  A highly effective method for the synthesis of the core indolo[2,3-a]quinolizidine skeleton found in yohimbine is described. The reaction of N-monosubstituted thioamides with bromoalkenoyl chlorides furnishes thioisomunchnones as transient 1,3-dipoles that undergo ready intramolecular cycloaddition across the tethered pi-bond to give thio-bicycloannulated products in a one-pot operation. The stereochemical outcome of the intramolecular reaction is the consequence of an endo cycloaddition of the neighboring-bond across the transient thioisomunchnone dipole. A major limitation of the method is that when a hydrogen is present in the alpha-position of the thioamide the initially formed thio-N-acyliminium ion undergoes proton loss to produce a S ,N-ketene acetal at a faster rate than dipole formation. Treatment of tetrahydro-beta-carboline-1-thione with 2-bromooct-7-enoyl chloride followed by reductive removal of sulfur from the cycloadduct resulted in the formation of (+/-)-alloyahimbanone. Attempts to cycloadd the thioisomunchnone dipole across several nucleophilic-bonds failed, and instead, products derived from cyclization of the pi-bond onto the initially formed thio-N-acyliminium ion were formed. The resulting N,S-ketals were further converted into several tetrahydroisoquinoline alkaloids in good yield.