Enantioselective synthesis of the tetrahydro-6H-benzo[c]chromenes via Domino Michael-Aldol condensation: control of five stereocenters in a quadruple-cascade organocatalytic multi-component reaction

Organocatalytic domino oxa-Michael-Michael-Michael-aldol condensation of 2-((E)-2-nitrovinyl)phenol and 2 equiv of alpha,beta-unsaturated aldehydes (e.g., cinnamaldehyde) provided tetrahydro-6H-benzo[c]chromenes in high diastereoselectivity and high enantioselectivity (>99% ee). Structure of the adduct 4a was confirmed unambiguously by X-ray analysis. The diversity of the protocol was demonstrated by the chemo-differentiating three-component reactions (ABC type) affording the highly functionalized tetra hydro-6H-benzo[c]chromenes. (C) 2008 Elsevier Ltd. All rights reserved.