Organocatalytic Michael/Michael Cycloaddition Enabled Asymmetric Construction of Hexahydroxanthones with Skeletal Diversity

Abstract

Abstract A highly efficient strategy for stereocontrolled construction of potentially bioactive and structurally rigid isoxazole‐fused spirocyclohexane oxindole‐based hexahydroxanthones via an organocatalytic domino Michael/Michael cycloaddition of multifunctional chromone‐based oxindole as a 4C building block and 3‐methyl‐4‐nitro‐5‐alkenyl‐isoxazole as an activated Michael acceptor is reported. Complex and skeleton‐diversified hexahydroxanthones bearing five continuous stereocenters including one spiro quaternary carton center were smoothly afforded in up to 92% yield, >20:1 d.r. and >99% ee. Further transformation of the product into other potentially bioactive molecules has also been demonstrated. This method could also forge the libraries of medicinally relevant molecules with skeletal diversity, thus to facilitate the search for new bioactive entities. magnified image