High-turnover copper-catalyzed amination of aryl bromides: exploring catalyst and ligand degradation pathways
File(s)
Published version
Author(s)
Tania, Di Felice
Chen, Troy Yu-Ting
Sale, David
Braddock, Chris
Davies, Rob
Type
Journal Article
Abstract
Copper-catalyzed Ullmann-type amination has emerged as a cost-effective and sustainable alternative to palladium-based C–N coupling, yet its broader adoption is often limited by high catalyst loadings. These high loadings arise in part from catalyst deactivation pathways that are still not fully understood. In this study, we examine the mechanism and stability of a homogeneous copper–oxalamide catalytic system for the coupling of aryl bromides with primary amines. As well as revealing mechanistic insight into the catalytic process, these kinetic studies show that under these conditions (EtOH solvent and KOH base) the copper centre is remarkably robust, but the oxalamide ligand undergoes rapid base-mediated hydrolysis, thus establishing ligand decomposition as a key limitation to catalyst longevity. By compensating for this ligand instability through controlled excess, we are able to achieve exceptionally low copper loadings of 5–50 ppm, delivering turnover numbers in copper of up to 7 × 104 for aryl bromides and 2 × 105 for aryl iodides. These findings further highlight copper's potential as a greener alternative to palladium in pharmaceutical and agrochemical synthesis and provide a foundation for further ligand design taking into account both catalyst stability and activity.
Date Issued
2026-07-29
Date Acceptance
2026-06-29
Citation
RSC Advances, 2026, 16 (35), pp.36665-36672
ISSN
2046-2069
Publisher
The Royal Society of Chemistry
Start Page
36665
End Page
36672
Journal / Book Title
RSC Advances
Volume
16
Issue
35
Copyright Statement
© 2026 The Author(s). Published by the Royal Society of Chemistry This article is licensed under a Creative Commons Attribution 4.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.
License URL
Identifier
10.1039/d6ra05376a
Publication Status
Published
Date Publish Online
2026-07-03