NHC-Catalyzed Asymmetric [4 + 2] Annulation of 2-Methylindole-3-Carbaldehydes to Spiro Indole-Fused Heterocycles

Abstract

Abstract Indole-fused heterocyclic compounds play a crucial role in drug development. Cycloaddition reactions represent an effective strategy for the construction of such compounds. While indole derivatives often serve as C3 synthons in these reactions, there are relatively few examples of indole derivatives acting as C4 synthons. Herein, we report an NHC-catalyzed activation of 2-methylindole-3-carbaldehyde, affording ortho-quinodimethane (o-QDM) as a key four-carbon synthon. The reaction proceeds under mild conditions with facile operation, affording spirocyclic indole-fused heterocyclic derivatives in moderate yields with excellent enantioselectivities.