3-(3-(1-methylindolyl))cyclopentanone | 220970-48-9

• 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-(3-(1-methylindolyl))cyclopentanone
• 英文别名: 3-(N-methyl-3-indolyl)-cyclopentan-1-one；3-(1-methyl-1H-indol-3-yl)cyclopentanone；Cyclopentanone, 3-(1-methyl-1H-indol-3-yl)-；3-(1-methylindol-3-yl)cyclopentan-1-one
• CAS: 220970-48-9
• 化学式: C₁₄H₁₅NO
• 分子量: 213.279
• InChiKey: ZDAWTASYTNCCCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  ethyl (1R,2S)-2-(1-methylindol-3-yl)-5-oxocyclopentane-1-carboxylate 在 sodium chloride 作用下， 以 水 、 二甲基亚砜 为溶剂， 以82%的产率得到3-(3-(1-methylindolyl))cyclopentanone
  参考文献：
  名称：

  Cross-Dehydrogenative Couplings between Indoles and β-Keto Esters: Ligand-Assisted Ligand Tautomerization and Dehydrogenation via a Proton-Assisted Electron Transfer to Pd(II)

  摘要：

  Cross-dehydrogenative coupling reactions between beta-ketoesters and electron-rich arenes, such as indoles, proceed with high regiochemical fidelity with a range of beta-ketoesters and indoles. The mechanism of the reaction between a prototypical beta-ketoester, ethyl 2-oxocyclopentanonecarboxylate, and N-methylindole has been studied experimentally by monitoring the temporal course of the reaction by H-1 NMR, kinetic isotope effect studies, and control experiments. DFT calculations have been carried out using a dispersion-corrected range-separated hybrid functional (omega B97X-D) to explore the basic elementary steps of the catalytic cycle. The experimental results indicate that the reaction proceeds via two catalytic cycles. Cycle A, the dehydrogenation cycle, produces an enone intermediate. The dehydrogenation is assisted by N-methylindole, which acts as a ligand for Pd(II). The computational studies agree with this conclusion, and identify the turnover-limiting step of the dehydrogenation step, which involves a change in the coordination mode of the beta-keto ester ligand from an O,O'-chelate to an beta'-bound Pd enolate. This ligand tautomerization event is assisted by the if-bound indole ligand. Subsequent scission of the beta'-C-H bond takes place via a proton-assisted electron transfer mechanism, where Pd(II) acts as an electron sink and the trifluoroacetate ligand acts as a proton acceptor, to produce the Pd(0) complex' of the enone intermediate. The coupling is completed in cycle B, where the enone is coupled with indole. Pd(TFA)(2) and TFA-catalyzed pathways were examined experimentally and computationally for this cycle, and both were found to be viable routes for the coupling step.

  DOI：

  10.1021/ja501681y

文献信息

• The ultra high pressure conjugate addition of indoles to electron-deficient olefins
  作者：Paul Harrington、Michael A Kerr

  DOI：10.1139/v98-158

  日期：1998.9.1

  The addition of indole and methyl indole at both high and ambient pressures to a series of Michael acceptors under the influence of ytterbium triflate was investigated. Under ambient pressure the more reactive and less sterically hindered electrophiles gave the expected 3-alkylated indoles in good to excellent yields. The more problematic Michael acceptors were subjected to pressures of 13 kbar. In

  研究了在三氟甲磺酸镱的影响下，在高压和环境压力下将吲哚和甲基吲哚添加到一系列迈克尔受体中。在环境压力下，反应性更强且空间位阻较小的亲电子试剂以良好至极好的产率得到预期的 3-烷基化吲哚。问题较多的迈克尔受体承受 13 kbar 的压力。在所有情况下，都观察到反应时间的显着减少和产率的显着提高。在涉及 3-methylcyclohex-2-en-1-one 的情况下，形成了副产物并通过单晶 X 射线衍射表征。α、β-不饱和酮的产率最高。Enals 倾向于聚合，而 enoates 被证明太不活泼了。
• Ruthenium-catalyzed direct C3 alkylation of indoles with α,β-unsaturated ketones
  作者：Shuai-Shuai Li、Hui Lin、Xiao-Mei Zhang、Lin Dong

  DOI：10.1039/c4ob02124j

  日期：——

  paper, a simple and highly efficient ruthenium-catalyzed direct C3 alkylation of indoles with various alpha,beta-unsaturated ketones without chelation assistance has been developed. This novel C-H activation methodology exhibits a broad substrate scope such as different substituted indoles, pyrroles, and other azoles. Further synthetic applications of the alkylation products can lead to more attractive

  本文研究了一种简单高效的钌催化的吲哚类化合物，具有多种α，β-不饱和酮，且没有螯合辅助，直接被C3烷基直接烷基化。这种新颖的CH活化方法具有广泛的底物范围，例如不同的取代吲哚，吡咯和其他唑类。烷基化产物的进一步合成应用可导致更具吸引力的3,4-稠合三环吲哚。
• Hafnium Trifluoromethanesulfonate [Hf(OTf)₄]-Catalyzed Conjugate ­Addition of Indoles to α,β-Enones
  作者：Motoi Kawatsura、Sachiko Aburatani、Junichi Uenishi

  DOI：10.1055/s-2005-872694

  日期：——

  Hafnium trifluoromethanesulfonate [Hf(OTf)4]- and scandium trifluoromethanesulfonate [Sc(OTf)3]-catalyzed conjugated addition of 3-position of indoles to several enones proceeded in acetonitrile as solvent. Especially, Hf(OTf)4 exhibited high catalytic ­activity and gave the conjugate addition product in good yield.

  氟化铪三氟甲磺酸盐 [Hf(OTf)4]- 和氟化 scandium 三氟甲磺酸盐 [Sc(OTf)3]- 催化了吲哚 3 位与多种烯酮的共轭加成反应，反应在乙腈溶剂中进行。特别是，Hf(OTf)4 显示出很高的催化活性，且得到的共轭加成产物收率良好。
• Carbohydrate-Based Tolylsulfonyl Hydrazines: Effective Catalysts for Michael Addition of Indoles to Electron-Deficient Olefins in Water
  作者：Jiwen Cai、Peng Wu、Yiqian Wan

  DOI：10.1055/s-2008-1072735

  日期：2008.5

  Carbohydrate-based tolylsulfonyl hydrazines were used for the first time to catalyze the Michael reaction of indoles to electron-deficient olefins in aqueous media to afford 3-substituted indole derivatives in good to excellent yields at room temperature.

  首次使用基于碳水化合物的托尔烷基磺酰肼催化吲哚与电子缺乏的烯烃在水相介质中进行迈克尔反应，顺利获得3-取代的吲哚衍生物，产率良好至优异，反应在室温下进行。
• Sulfamic acid as a cost-effective and recyclable solid acid catalyst for Friedel–Crafts alkylation of indole with α,β-unsaturated carbonyl compound and benzyl alcohol
  作者：Jing Yang、Juan Zhang、Tian Tian Chen、De Mei Sun、Ji Li、Xue Fen Wu

  DOI：10.1016/j.cclet.2011.06.006

  日期：2011.12

  Abstract Sulfamic acid was proved to be a cost-effective and recyclable catalyst for Friedel–Crafts type reaction of indole with α , β -unsaturated carbonyl compound and benzyl alcohol. Various indoles, α , β -unsaturated carbonyl compounds and a benzyl alcohol were successfully used in this type of reaction, and the corresponding products were obtained in good to excellent yields.

  摘要氨基磺酸被证明是吲哚与α，β-不饱和羰基化合物和苯甲醇的Friedel-Crafts型反应的一种经济高效且可回收的催化剂。在这种类型的反应中成功使用了各种吲哚，α，β-不饱和羰基化合物和苯甲醇，并以良好或优异的收率获得了相应的产物。