Solvent directed base-enabled diastereodivergent domino cycloaddition of isoxazole–oxindole styrenes and Michael additions of isoxazole–styrenes with vinyl malononitriles

Abstract

A base-catalyzed strategy for the diastereodivergent synthesis of complex spirocyclic oxindoles and linear Michael's adducts are disclosed. Isoxazole–styrene derivatives display dual reactivity: 3-methyl-4-nitro-5-isatylidenyl-isoxazole undergoes a domino vinylogous 1,4-Michael addition/intramolecular cyclization with vinyl malononitriles to afford spiro[indoline-3,2′-naphthalene]-4′-carbonitriles in good to excellent yields. Remarkably, solvent control enables exclusive access to two specific diastereomers. These scalable and operationally simple protocols deliver two distinct classes of valuable isoxazole-derived products, underscoring the unique reactivity of this scaffold.