(1R,2S)-(1S,2R,4R)-2-ethyl-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl 2-(1-methyl-1H-indol-3-yl)-5-oxocyclopentanecarboxylate | 1598431-87-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (1R,2S)-(1S,2R,4R)-2-ethyl-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl 2-(1-methyl-1H-indol-3-yl)-5-oxocyclopentanecarboxylate
• CAS: 1598431-87-8
• 化学式: C₂₇H₃₅NO₃
• 分子量: 421.58
• InChiKey: OWFOZVVQSHYVKX-JDKAPYAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.78
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  48.3
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  1-methyl-3-deuterio-1H-indole 在 palladium(II) trifluoroacetate 、 溶剂黄146 作用下， 以 二氧六环-d8 、 异丙醇 为溶剂， 反应 17.08h， 生成 (1R,2S)-(1S,2R,4R)-2-ethyl-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl 2-(1-methyl-1H-indol-3-yl)-5-oxocyclopentanecarboxylate 、 (1S,2R,4R)-2-ethyl-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl 2-(1-methyl-1H-indol-3-yl)-5-oxocyclopentanecarboxylate
  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