Organocatalytic Aza-Michael/Mannich Cascade Reaction: Synthesis of Enantioenriched 3,3′-Spirooxindole γ‑Lactams

Highly enantioselective synthesis of 3,3′-spirooxindole γ-lactams with three contiguous stereocenters (two quaternary) was achieved. The aza-Michael/Mannich cascade reaction of α-imine-β-oxobutanamides and methyleneindolinones catalyzed by a bifunctional diaminocyclohexane-derived thiourea catalyst gave the desired products in moderate to good yields (up to 78%), moderate to good diastereoselectivities (up to 10:1 dr), and good to excellent enantioselectivities (up to >99% ee). A gram-scale synthesis and some transformations of 3,3′-spirooxindole γ-lactams were also carried out.