Organocatalytic Desymmetric Spirocyclization of Enone-Tethered 2,5-Cyclohexadienone with Isoxazolines to Access Enantioenriched Spiro-Fused Scaffolds

Enantioselective desymmetric spirocyclization is a powerful tool for concisely generating intricate 3D molecular architectures from readily accessible substrates. Herein, we report an organocatalytic desymmetric spirocyclization of enone-tethered 2,5-cyclohexadienone with 3-arylisoxazol-5(4<i>H</i>)-one to access enantioenriched spiro-fused scaffolds featuring four consecutive stereogenic centers in high yields and excellent diastereo- and enantioselectivities. This protocol could proceed smoothly under parts per million-level organocatalyst loading. Furthermore, the reusability of the catalyst and various intriguing derivatizations of the title product highlight its synthetic utility.