Synthesis of Spiro-imidazole-4(2H)-ones via a Cascade Aza-Mannich/Cyclocondensation Reaction Using N-Unprotected Ketimines with α-Ketoamides.

Imidazole-4(2H)-ones are extensively studied in synthetic chemistry communities as important motifs and exhibit intriguing biological activities that are crucial for lead compound discovery. Thus, the development of efficient and green synthetic strategies for the preparation of imidazole-4(2H)-ones has attracted significant attention. Herein, a catalyst-free cascade annulation reaction of isatin-derived N-unprotected ketimines with α-ketoamides is reported, furnishing a variety of spiro-imidazole-4(2H)-one oxindole derivatives in good to excellent yields. Furthermore, gram-scale preparation and synthetic transformations demonstrate the practicality and utility of the current cascade reaction.