Enantioselective access to 3,3'-disubstituted oxindole derivatives by N-heterocyclic carbene catalysis.

Abstract

An effectively enantioselective and regioselective N-heterocyclic carbene-catalyzed oxidative spiroannulation of isatin-derived enals with 2,4-dioxoesters to directly synthesize spirooxindole δ-lactones was realized. Subsequently, upon treatment with methanol under reflux, spirooxindole δ-lactones were effectively converted into acyclic 3,3'-disubstituted oxindole derivatives bearing an all-carbon quaternary center that might have been obtained through a novel sequence of deesterification and decarbonylation paths. This approach was qualified with a broad substrate scope and mild reaction conditions, achieving moderate to excellent yield and enantioselectivity. In addition, scale-up experiments and the synthetic transformations of spirooxindole δ-lactones and acyclic 3,3'-disubstituted oxindole derivatives further highlighted the synthetic utility.