A Brønsted Acid-Catalyzed Multicomponent Reaction for the Synthesis of Highly Functionalized γ-Lactam Derivatives

Molecules. 2019 Aug 14;24(16):2951. doi: 10.3390/molecules24162951.

Abstract

Brønsted acids catalyze a multicomponent reaction of benzaldehyde with amines and diethyl acetylenedicarboxylate to afford highly functionalized γ-lactam derivatives. The reaction consists of a Mannich reaction of an enamine to an imine, both generated in situ, promoted by a phosphoric acid catalyst and a subsequent intramolecular cyclization. The hydrolysis of the cyclic enamine substrate can provide enol derivatives and, moreover, a second attack of the amine on the carboxylate can afford amide derivatives. An optimization of the reaction conditions is presented in order to obtain selectively cyclic enamines that can afford the enol species after selective hydrolysis.

Keywords: multicomponent reactions; organocatalysis; pyrrolidones; γ-lactam.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Catalysis
  • Chemistry Techniques, Synthetic
  • Combinatorial Chemistry Techniques
  • Lactams / chemical synthesis*
  • Lactams / chemistry
  • Lactams / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure

Substances

  • Anti-Bacterial Agents
  • Lactams