Enantioselective and Diastereoselective Synthesis of Multisubstituted Spirocyclopentane Oxindoles through NHC Catalysis.

Abstract

The highly enantio- and diastereoselective N-heterocyclic carbene-catalyzed [3 + 2] annulation of isatin-derived enals and α-EWG-functionalized chalcones is disclosed. Developed herein is an efficient, operationally simple, and general synthetic protocol for the straightforward construction of spirocyclopentane oxindole scaffolds bearing cyano or nitro substituents in acceptable to good yields under mild conditions. Based on the obtained products, we propose that a novel pathway occurs subsequent to the first nucleophilic addition step. This protocol features broad substrate scope and high functional group tolerance, enabling late-stage functionalization and efficient construction of structurally complex marketed bioactive compounds. In addition, gram-scale synthesis further highlights the synthetic utility of this method.