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Highly diastereoselective four-component synthesis of polysubstituted 2-piperidinones with three and four stereogenic centers

  • Anatoly N. VereshchaginEmail author
  • Kirill A. Karpenko
  • Michail N. Elinson
  • Alexander S. Goloveshkin
  • Evgeniya O. Dorofeeva
  • Mikhail P. Egorov
Article

Abstract

A novel four-component diastereoselective synthesis of polysubstituted 2-piperidinones is reported. The Michael addition–Mannich cascade of benzylidenemalononitriles or benzylidenecyanoacetates, dialkyl malonates, aromatic aldehydes and ammonium acetate in alcohols provides convenient access to alkyl (±)-5,5-dicyano-2-oxo-4,6-diarylpiperidine-3-carboxylates with three stereocenters in 66–92% or dialkyl (±)-2,4-diaryl-3-cyano-6-oxopiperidine-3,5-dicarboxylates with four stereocenters in 62–90%. The formation of products was highly stereoselective, with only one diastereomer formed. Ammonium acetate plays a dual role, acting as a base and as a nitrogen source. Structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR, IR, elemental analysis and mass spectral studies. The formation of a single diastereomer was confirmed by singe-crystal X-ray diffraction studies.

Graphic abstract

Keywords

Four-component reaction Polysubstituted 2-piperidinones Aromatic aldehydes Olefins Dialkyl malonates Ammonium acetate Stereoselectivity 

Notes

Acknowledgements

This work was supported by the Russian Science Foundation (RSF Grant 17-73-20260).

Supplementary material

11164_2019_4027_MOESM1_ESM.docx (2.7 mb)
Supplementary material 1 (DOCX 2778 kb)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.N. D. Zelinsky Institute of Organic ChemistryMoscowRussian Federation
  2. 2.A. N. Nesmeyanov Institute of Organoelement CompoundsMoscowRussian Federation

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