Asymmetric Synthesis of C2-Quaternary Indolin-3-ones Enabled by N-Heterocyclic Carbene Catalysis

Abstract

An N-heterocyclic carbene (NHC)-catalyzed formal [4 + 2] annulation of 2-aryl-3 H-indol-3-ones with α,β-unsaturated carboxylic acids bearing γ-H was developed via an in situ activation strategy. The reaction involves the γ-addition of vinyl enolates to the unique cyclic ketimines to afford chiral tricyclic indolin-3-ones with a quaternary carbon center at 2-position. This protocol provides a rapid and enantioselective pathway to access a novel class of structurally important C2-quaternary indolin-3-ones that might be useful for drug discovery.