Stereoselective aza Diels-Alder reaction on solid phase: a facile synthesis of hexahydrocinnoline derivatives

J Comb Chem. 2007 Mar-Apr;9(2):263-6. doi: 10.1021/cc060125l.

Abstract

As part of our continuing studies of polymer-supported pericyclic reactions for preparing biologically interesting heterocyclic compounds, we have introduced a traceless solid-phase synthesis of hexahydrocinnolines. We developed a method in which mild reaction conditions can be used for the hetero-Diels-Alder reactions on a polymeric support. The dienoic 3-vinyl-2-cyclohexenol attached to a Wang resin through an ether linkage undergoes [4 + 2] cycloaddition reaction with several azadienophiles. The highly stereoselective Diels-Alder reaction showed preferential formation of a single cycloadduct resulting from an anti attack of the dienophile on the polymer-bound diene. Trifluoroacetic acid-mediated cleavage of the polymer-bound cycloadducts yields fused nonaromatic hexahydrocinnolines in moderate yields in three steps.

MeSH terms

  • Aza Compounds / chemistry*
  • Heterocyclic Compounds, 2-Ring / chemical synthesis*
  • Models, Molecular
  • Stereoisomerism

Substances

  • Aza Compounds
  • Heterocyclic Compounds, 2-Ring
  • cinnoline