Organocatalytic Oxa-Michael/Michael/Michael/Aldol Condensation Quadruple Domino Sequence: Asymmetric Synthesis of Tricyclic Chromanes

Abstract

An efficient and highly stereoselective one-pot, four-component synthesis of functionalized tricyclic chromanes has been achieved through an organocatalyzed quadruple domino reaction. The reaction sequence involves an oxa-Michael/Michael/Michael/aldol condensation between alcohols, 2 equiv of acrolein, and nitrochromenes to generate the pharmaceutically important tricyclic chromanes bearing three contiguous stereogenic centers including a chiral tetrasubstituted carbon center in good domino yields (30-70%) and excellent diastereo- and enantioselectivities (>20:1 dr and >99% ee).