Atroposelective Synthesis of Planar-Chiral Indoles via Carbene Catalyzed Macrocyclization.

Abstract

Indole-based planar-chiral macrocycles are widely found in natural products and bioactive molecules. However, in sharp contrast to the preparation of indole-based axially chiral structures, the enantioselective catalysis of indole-based planar-chiral macrocycles is still a formidable task so far. Here we report an N-heterocyclic carbene (NHC)-catalyzed intramolecular atroposelective macrocyclization of 3-carboxaldehyde indole/pyrroles, featuring with broad substrate scope and good functional group tolerance, and allowing for a rapid access to diverse indole/pyrrole-based planar-chiral macrocycles with various tether-lengths (10-16 members) in good yields and with excellent enantioselectivities. Importantly, the indole-based macrocyclic structures with both planar and axial chirality were directly and efficiently obtained through this protocol with excellent enantioselectivities and diastereoselectivities. In addition, these synthesized planar-chiral macrocycles offer many possibilities for chemists to develop new catalysts or ligands, as well as new reactions.