Enantioselective Diels-Alder-lactamization organocascades employing a furan-based diene

Org Biomol Chem. 2017 Apr 11;15(15):3179-3183. doi: 10.1039/c6ob02738e.

Abstract

α,β-Unsaturated acylammonium salts are useful dienophiles enabling highly enantioselective and stereodivergent Diels-Alder-initiated organocascades with furan-based dienes. Complex polycyclic systems can thus be obtained from readily prepared dienes, commodity acid chlorides, and a chiral isothiourea organocatalyst under mild conditions. We describe the use of furan-based dienes bearing pendant sulfonamides leading to the generation of oxa-bridged, trans-fused tricyclic γ-lactams. This process constitutes the first highly enantio- and diastereoselective, organocatalytic Diels-Alder cycloadditions with these typically problematic dienes due to their reversibility. Computational studies suggest that the high diastereoselectivity with these furan dienes may be due to a reversible Diels-Alder cycloaddition for the endo adducts. In addition, the utility of this methodology is demonstrated through a concise approach to a core structure with similarity to the natural product isatisine A and a nonpeptidyl ghrelin-receptor inverse agonist.

MeSH terms

  • Alkenes / chemistry*
  • Catalysis
  • Furans / chemistry*
  • Lactams / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Stereoisomerism
  • Thermodynamics

Substances

  • Alkenes
  • Furans
  • Lactams
  • furan