Addition of a Carbene Catalyst to Indole Aryl Aldehyde Activates a Remote δ-sp² Carbon for Protonation and Formal [4+2] Reaction

Abstract

The addition of a carbene catalyst to an indole aryl aldehyde leads to the activation of a remote sp² carbon that is five atoms away from the catalyst. The unsaturated Breslow intermediate formed between the catalyst and substrate undergoes an internal redox reaction and remote carbon protonation to generate an analogous azolium vinyl enolate intermediate. Subsequent [4+2] reaction with cyclic imine substrates eventually affords multicyclic pyridoindoles as nearly single diastereomers with excellent enantioselectivities.