Multicomponent Synthesis of Spiro-dihydropyridine Oxindoles via Cascade Spiro-cyclization of Knoevenagel/Aza-Michael Adducts

J Org Chem. 2022 Nov 4;87(21):13556-13563. doi: 10.1021/acs.joc.2c01063. Epub 2022 Oct 4.

Abstract

An efficient, straightforward, and one-pot synthesis of biologically relevant spiro-dihydropyridine oxindoles was described via readily available isatin, malononitrile, allenoate, and amines. The metal/organocatalyst-free, Et3N-mediated reaction proceeds via cascade spiro-cyclization of in situ generated Knoevenagel/aza-Michael adducts. The reaction has great flexibility over electron-rich and electron-poor substituents affording desired products in good to excellent yields. We have also demonstrated the selected spiro-dihydropyridines for late-stage diversification into new spiro-dihydropyridine hybrids of pharmaceutical relevance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Cyclization
  • Dihydropyridines*
  • Molecular Structure
  • Oxindoles
  • Spiro Compounds*
  • Stereoisomerism

Substances

  • Oxindoles
  • 1,4-dihydropyridine
  • Spiro Compounds
  • Dihydropyridines