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 interaction 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 α‐methylene‐γ‐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. One thing leads to another: Amide allylation of various isatin substrates with NH‐containing stannylated reagents resulted in extremely high yields and enantioselectivities of variously substituted homoallylic alcohols, thereby allowing convenient access to chiral 2‐oxindoles spiro‐fused to the α‐methylene‐γ‐butyrolactone functionality and their halogenated derivatives in almost enantiopure forms (see scheme).