Catalytic Enantioselective Amide Allylation of Isatins and Its Application in the Synthesis of 2-Oxindole Derivatives Spiro-Fused to the α-Methylene-γ-Butyrolactone Functionality

This article is a full account of the work exploring the potential utility of catalytic enantioselective amide allylation of various isatins using indium-based chiral catalysts. A survey of various isatin substrates and NH-containing stannylated reagents revealed that the reaction has a remarkably wide scope to result in extremely high yields and enantioselectivities (up to > 99 %, 99% ee) of variously substituted homoallylic alcohols. Several mechanistic investigations demonstrated that the substrate-reagent hydrogen-bond inter-action plays a critical role in the formation of the key transition states to result in enhanced catalytic reaction. The success of this approach allowed convenient access to chiral 2-oxindoles spiro-fused to the alpha-methylene-gamma-butyrolactone functionality and their halogenated derivatives in almost enantiopure forms, thus highlighting the general utility of this synthetic method to deliver a large variety of antineoplastic drug candidates and pharmaceutically meaningful compounds.