Palladium-Catalyzed Asymmetric (4+2) Annulation of γ-Methylidene-δ-valerolactones with Alkenes: Enantioselective Synthesis of Functionalized Chiral Cyclohexyl Spirooxindoles

An unprecedented asymmetric catalytic (4 + 2) annulation reaction of aryl-substituted gamma-methylidene-delta-valerolactones (GMDVs) with isatin-derived para-quinone methides (p-QMs) has been developed under the catalysis of palladium(0) and (S,S,S)-(-)-Xyl-SKP, offering a new approach for the diastereo-and enantioselective synthesis of chiral cyclohexadienone-fused cyclohexyl spirooxindoles. Significantly, three highly congested contiguous tetrasubstituted carbon atoms embedded in bispir-ocyclic skeleton, of which two are vicinal quaternary stereogenic centers, are forged in an effective and selective manner (up to 99% yield, up to 95% ee, >20/1 dr). The current reaction represents the first exploration of enantioselective catalytic (4 + 2) annulation forming the six-membered carbocycles in the chemistry of both GMDVs and p-QMs.

Automated summary

An unprecedented asymmetric catalytic (4 + 2) annulation reaction has been developed for the synthesis of chiral cyclohexadienone-fused cyclohexyl spirooxindoles using aryl-substituted gamma-methylidene-delta-valerolactones (GMDVs) and isatin-derived para-quinone methides (p-QMs) catalyzed by palladium(0) and (S,S,S)-(-)-Xyl-SKP. This reaction can efficiently and selectively forge three highly congested contiguous tetrasubstituted carbon atoms, including two vicinal quaternary stereogenic centers.