Asymmetric Organocatalytic [4 + 1] Annulations: Enantioselective Construction of Multifunctionalized Spirocyclopentane Oxindoles Bearing α,α-Disubstituted α-Amino-β-keto Esters

The highly enantioselective preparation of spirooxindoles bearing α,α-disubstituted α-amino-β-keto esters was achieved through [4 + 1] annulation of oxindoles and α-imine-β-oxo-γ,δ-unsaturated esters under mild conditions in good yields (up to 82%) and stereoselectivities (up to >20:1 dr, 96% ee). The reaction is amenable to gram scale synthesis using catalyst loading as low as 1 mol %.

The corresponding chiral α,α-disubstituted α-amino-β-keto esters could be easily transformed into cyclopenta[ b]indole derivatives without erosion of enantiopurity.