Asymmetric Organocatalytic Quadruple Cascade Reaction of 2-Hydroxychalcone with Cinnamaldehyde for the Construction of Tetrahydro-6H-benzo[c]chromene Containing Five Stereocenters

An asymmetric organocatalytic quadruple cascade reaction was developed for the stable and sterically hindered 2-hydroxychalcones and substituted cinnamaldehydes. This process proceeded through an oxa-Michael-Michael-Michaelaldol condensation to afford highly functionalized tetrahydro-6H-benzo[c] chromene derivatives with high dia-stereoselectivity and enantioselectivity (>99% ee). The structure of adduct 4g with five stereocenters was unambiguously confirmed by single-crystal X-ray diffraction, and valuable mass spectrometry data provided direct support for the proposed reaction mechanism.