N-Heterocyclic Carbene-Catalyzed (3 + 3) Annulation for the Diastereo- and Atroposelective Synthesis of N–N Axially Chiral Quino(xa)linones
Abstract
Atroposelective synthesis of N–N axial compounds remains a relatively underexplored area due to the challenges such as low rotational barriers and configurational instability of N–N bonds, despite their presence in bioactive molecules and functional ligands. Herein, we report a transition-metal-free, N-heterocyclic carbene (NHC)-catalyzed oxidative (3 + 3) annulation strategy for the atroposelective synthesis of N–N axially chiral quinoxalinones and quinolinones. The reaction proceeds via the generation of the chiral α,β-unsaturated acylazolium intermediate and delivers a broad range of products in moderate-to-excellent yields with high diastereo- and enantioselectivities under mild and metal-free conditions. Experimental and DFT studies confirmed significant configurational stability of the N–N axis with rotational barriers >36 kcal/mol. This methodology is likely to provide a versatile approach to constructing stable N–N axially chiral frameworks, expanding the scope of organocatalytic atroposelective synthesis beyond conventional C–C and C–N axially chiral frameworks.
Fields of Study & Subjects
Axial and Atropisomeric Chirality Synthesis
N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
Pharmacological Receptor Mechanisms and Effects
Publication details
- Journal / source
- ACS Sustainable Chemistry & Engineering
- Publisher
- American Chemical Society (ACS)
- Volume
- 14
- Issue
- 10
- Pages
- 5238–5247
- Publication date
- 3 March 2026
- Language
- EN