N-Heterocyclic Carbene-Catalyzed (3 + 3) Annulation for the Diastereo- and Atroposelective Synthesis of N–N Axially Chiral Quino(xa)linones

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Authors: Sowmya Shree Ranganathappa, Krishnendhu Karickal Radhakrishnan, Fathima Dinsha Paravakkal, Akkattu T. Biju
Cited by: 3
References: 89

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