A bifunctional pyrazolone–chromone synthon directed organocatalytic double Michael cascade reaction: forging five stereocenters in structurally diverse hexahydroxanthones

Abstract

The merging of two or more known natural product-based scaffolds is a powerful and routine strategy to develop bioactive small molecules. Here, we wish to report the first example of the bifunctional pyrazolone–chromone synthon 1 directed organocatalytic double Michael tandem reaction, which serves as a fruitful strategy for the facile access to structurally diverse hexahydroxanthone derivatives 3 and 5 bearing five continuous stereocenters, including two all-carbon quaternary spiro-stereocenters. These products were smoothly afforded in up to 87% yield, >20 : 1 dr and >99% ee under mild conditions. This is also the first example of catalytic enantioselective access to spirocyclohexanebenzofuranones and bispirocarbocyclic pyrazolones, potentially useful in medicinal chemistry.