Enantioselective Construction of Polycyclic Chromanes through Organocatalytic Multicomponent Quintuple Reaction via One-pot Sequential Procedure

An efficient and highly stereoselective synthetic method access to polycyclic chromanes has been achieved through organocatalyzed three-component reactions involving 2-hydroxycinnamaldehydes, 2-aminochalcones, and malononitrile as substrates. The reactions underwent a quintuple process by aza-Michael/Michael/Knoevenagel/oxa-Michael/aldol-type reaction in sequence to give products bearing 3 new generated rings and 5 chiral centers in moderate to quantitative yields with excellent enantioselectivities. A novel retro-reaction mechanism was discovered in the synthetic transformations of products.