Highly stereoselective organocatalytic synthesis of pyrrolidinyl spirooxindoles containing halogenated contiguous quaternary carbon stereocenters

Abstract

The highly stereoselective synthesis of pyrrolidine-fused spirooxindole derivatives bearing a carbon-halogen bond and contiguous quaternary carbon stereocenters was achieved via a [3 + 2] cycloaddition reaction. This method provided facile access to a collection of enantiomerically pure spiro[pyrrolidin-3,2′-oxindoles] containing halogenated contiguous quaternary carbon stereocenters in good to high yields (48–84%) and excellent stereoselectivity (up to >20:1 dr and >99% ee). The halogen-containing products can be stereoselectively transformed into sulfurated derivatives via nucleophilic substitution (SN2) reactions, indicating that they may serve as candidates in the development of covalent inhibitors with potential biological activity.