Organocatalytic Enantioselective 1,3-Dipolar Cycloadditions between Seyferth-Gilbert Reagent and Isatylidene Malononitriles: Synthesis of Chiral Spiro-phosphonylpyrazoline-oxindoles

A new method has been developed for the catalytic enantioselective 1,3-dipolar cycloaddition of the Seyferth-Gilbert reagent (SGR) to isatylidene malononitriles using a cinchona alkaloid derivative as a catalyst. This method allowed for the synthesis of a series of chiral spiro-phosphonylpyrazoline-oxindoles in good yields with excellent enantioselectivities. The synthetic utility of this method was further demonstrated by its use in a three-component domino reaction involving isatin, malononitrile, and SGR based on sequential Knoevenagel condensation and 1,3-dipolar cycloaddition reactions.