Atroposelective Synthesis of N–N Axially Chiral Indoles and Pyrroles via NHC-Catalyzed Diastereoselective (3 + 3) Annulation Strategy

The synthesis of N–N axially chiral molecules
in the enantiopure
form has emerged as an interesting research topic primarily due to
the significance and intricacy in synthesizing these molecules, especially
bearing heterocyclic motifs. Herein, we disclose a method for the
introduction of N–N axial chirality along with a point chiral
center via the N-heterocyclic carbene (NHC)-catalyzed atroposelective
synthesis of dihydropyridinone-containing indoles and pyrroles. The
reaction follows a (3 + 3) annulation approach by the interception
of indole/pyrrole-derived enamines with α,β-unsaturated
aldehydes under oxidative NHC catalysis proceeding via the α,β-unsaturated
acylazoliums. The N–N axially chiral indoles/pyrroles were
formed under mild conditions in broad scope with high selectivity.
In addition, preliminary DFT studies of the N–N rotational
barrier of the axially chiral products were performed.