High diastereoselective amine-catalyzed Knoevenagel-Michael-cyclization-ring-opening cascade between aldehydes, 3-arylisoxazol-5(4H)-ones and 3-aminocyclohex-2-en-1-ones

Mol Divers. 2018 Aug;22(3):627-636. doi: 10.1007/s11030-018-9817-4. Epub 2018 Mar 20.

Abstract

A highly diastereoselective three-component cascade reaction among aromatic aldehydes, 3-arylisoxazol-5(4H)-ones and 3-aminocyclohex-2-en-1-ones takes place under the catalysis of triethylamine, providing (3SR,4SR)-4-aryl-3-[(E)-(hydroxyimino)(aryl)methyl]-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-diones in 45-85% yields. The transformation presumably proceeds through a sequential cascade of Knoevenagel/Michael-addition/cyclization/ring-opening reactions. This process was carried out in green media (EtOH/water, 1:1-1:3) at reflux. Products are crystallized directly from the reaction mixture and their isolation includes only filtration. The structure of (3SR,4SR)-3-[(E)-(hydroxyimino)(phenyl)methyl]-7,7-dimethyl-4-phenyl-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-dione was confirmed by X-ray diffraction analysis.

Keywords: 3-Aminocyclohex-2-en-1-ones; 3-Arylisoxazol-5(4H)-ones; Green synthesis; Knoevenagel–Michael-addition; MCRs; Multicomponent reactions; Octahydroquinolines; Stereoselectivity.

MeSH terms

  • Benzaldehydes / chemistry*
  • Catalysis
  • Cyclization
  • Cyclohexanones / chemistry*
  • Ethylamines / chemistry*
  • Green Chemistry Technology
  • Isoxazoles / chemistry*
  • Quinolines / chemistry*
  • Stereoisomerism

Substances

  • Benzaldehydes
  • Cyclohexanones
  • Ethylamines
  • Isoxazoles
  • Quinolines
  • benzaldehyde
  • triethylamine