Organocatalytic Enantioselective γ‑Position-Selective Mannich Reactions of β‑Ketocarbonyl Derivatives

Catalytic asymmetric Mannich reactions of β-ketocarbonyl derivatives (such as β-ketoesters and (2-oxopropyl)­phosphonate), resulting in the formation of a C–C bond at the γ-position of the β-ketocarbonyl derivatives with high enantioselectivities, are reported. The bond formation at the α-position of the β-ketoester was reversible, and the γ-position-reacted product δ-amino β-ketoester derivative was kinetically formed and was stable. The dynamic kinetic process was key for the direct access to the γ-position-reacted products from β-ketocarbonyls under catalytic conditions.