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Highly regio- and diastereoselective synthesis of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles, based on a post-Ugi condensation: joint experimental and computational study

Abstract

A novel series of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles were synthesized via a two-step pathway. In the first step, Ugi-four-component condensation of 2-formylindole, amines, (E)-4-alkoxy-4-oxobut-2-enoic acids, and isocyanides gave the corresponding Ugi-adducts. This adduct underwent intramolecular hydroamination in the presence of K2CO3 in CH3CN at room temperature to afford diastereoselective synthesis of a range of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles. A comparison of experimentally observed CD and UV–visible spectra with the theoretical DFT calculated ECD spectra was used to predict the major diastereomer.

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Acknowledgements

The authors would like to thank the Alzahra University and Iran National Science Foundation (INSF) for financial support. We are also very grateful for Prof. Adolf Gogoll and Dr. Sandra Olsson from Uppsala University (Uppsala, Sweden) for doing experimental ECD and UV–visible spectroscopy.

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Correspondence to Morteza Shiri or Majid M. Heravi.

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Shiri, M., Heravi, M.M., Zadsirjan, V. et al. Highly regio- and diastereoselective synthesis of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles, based on a post-Ugi condensation: joint experimental and computational study. J IRAN CHEM SOC 16, 1517–1526 (2019). https://doi.org/10.1007/s13738-019-01632-3

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Keywords

  • Ugi reaction
  • 2-Formylindole
  • Multicomponent reaction
  • α,β-Unsaturated acids
  • Cyclization
  • Intramolecular hydroamination
  • DFT
  • ECD spectra