Organocatalytic Asymmetric Four-Component [5+1+1+1] Cycloadditions via a Quintuple Cascade Process

An asymmetric four-component [5 + 1 + 1 +1] formal cycloaddition reaction of 3-substituted 2-cyclopentenones, activated methylene nucleophiles and two molecules of aldehydes is developed under chiral primary aminocatalysis, producing a diversity of highly enantioenriched fused and spirocyclic frameworks with high molecular complexity. Mechanism studies indicate that the current reaction proceeds in a challenging cascade quintuple Knoevenagel condensation/Michael addition/retro-Michael addition/Michael addition/Michael addition sequence via diverse aminocatalytic modes.