Asymmetric Organocatalytic [3 + 2]-Cycloaddition of <i>N</i>-Alkoxy-4-oxo-acrylamides with Isatin-Derived Ketimines: Access to Enantioselective Synthesis of Spirooxindole-imidazolidinones

The spirooxindole framework is a privileged motif in numerous biologically significant natural products and has been demonstrated as a crucial core scaffold in a variety of medicinally significant compounds. Herein, we achieved a highly efficient enantioselective [3 + 2]-cycloaddition reaction of <i>N</i>-alkoxy-4-oxo-acrylamides with isatin-derived ketimines. This method enabled the precise synthesis of chiral spirooxindole-imidazolidinone derivatives, which are notable for their intricate structures and the presence of chiral quaternary centers. Our approach utilized an organocatalytic strategy with a hydrogen-bonding bifunctional squaramide-based catalyst. This reaction demonstrated impressive results, achieving high yields and exceptional enantioselectivities of >99% ee for the majority of substrates, even when employing only 2 mol % of the catalyst.