N-Heterocyclic Carbene-Catalyzed (3 + 3) Annulation for the Diastereo- and Atroposelective Synthesis of N–N Axially Chiral Quino(xa)linones
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.
Authors
- Sowmya Shree Ranganathappa
- Akkattu T. Biju (ORCID: https://orcid.org/0000-0002-0645-8261)
- Fathima Dinsha Paravakkal
- Krishnendhu Karickal Radhakrishnan
Institutions
- Mahatma Gandhi University (IN)
- Indian Institute of Science Bangalore (IN)
Publication Details
- Journal
- ACS Sustainable Chemistry & Engineering
- Published
- 2026-03-03
- DOI
- https://doi.org/10.1021/acssuschemeng.6c00722
- Primary Topic
- Axial and Atropisomeric Chirality Synthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00