Chiral Bisguanidine-Catalyzed Inverse-Electron-Demand Hetero-Diels−Alder Reaction of Chalcones with Azlactones

A new type of C2-symmetric chiral bisguanidine was designed as a highly efficient catalyst in the inverse-electron-demand hetero-Diels−Alder reaction of chalcones with azlactones for the first time. A wide variety of γ,δ-unsaturated δ-lactone derivatives with α-quaternary-β-tertiary stereocenters were obtained in high yields (up to 88%) with excellent enantioselectivities (up to 99% ee). Hydrogen bonds were considered to be crucial for the activation and stereoinduction of the reaction. In all cases, the major was HDA adducts, which were obtained as a single diastereomer along with little amount of Michael addition products.