Reaction of dialkyl acetylenedicarboxylates with ninhydrin in the presence of secondary amines: synthesis of alkyl 4-(benzyl(alkyl)amino)-1′,3′,5-trioxo-1′,3′-dihydro-5H-spiro[furan-2,2′-indene]-3-carboxylate derivatives

A three-component domino reaction approach between a secondary amine, dialkyl acetylenedicarboxylate and ninhydrin that affords novel alkyl 4-(benzyl(alkyl)amino)-1',3',5-trioxo-1',3'-dihydro-5H-spiro[furan-2,2'-indene]-3-carboxylate derivatives is reported. The reaction sequence consists of an initial Michael-addition of secondary amines to dialkyl acetylenedicarboxylates, followed by aldol-like reaction with ninhydrin, and then gamma-lactonization to afford the products. This cascade reaction sequence represents a rapid and unprecedented route to the described biologically interesting molecules.