Nickel-Catalyzed de novo Synthesis of C─N Atropisomeric Biaryls via Dual Chelation-Assisted Aza-Michael Addition.

Authors

Xiaohan Zhu, Yue Shi, Wei Wang, Genping Huang, Xingwei Li

Published in

Angewandte Chemie (International ed. in English). Pages e6717102. Sep 10, 2026. Epub Sep 10, 2026.

Abstract

The asymmetric construction of C─N bonds using readily available C─H (arene) and N─H (amine) reagents constitutes a modular and flexible synthetic strategy. Nevertheless, de novo synthesis of axially chiral C─N scaffolds via direct C─H/N─H coupling remains a formidable challenge, and it has been previously restricted to organocatalysis using soft (more nucleophilic) NH indoles. Reported herein is a nickel-catalyzed oxidative coupling strategy that leverages the oxygen- or nitrogen-chelating group in the NH nucleophiles. The coupling system is applicable to three distinct classes of NH reagents, permitting asymmetric synthesis of diverse C─N atropisomers. Mechanistic studies reveal that the C─N formation is facilitated by a chelating group in the NH reagent through formation of a favored 5- and 7-membered ring-fused nickelacyclic transition state. This coupling system has addressed a series of challenges in intermolecular C─H/N─H cross-coupling by overcoming limited applicability of NH nucleophiles and the reliance on prefunctionalized electrophiles such as aryl halides and hypervalent iodines.

PMID:
42723298
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

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