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Cu-Catalyzed Coupling of Aryl Halides Utilizing Ammonia and Hydroxypicolinamide Ligands

David J. Bernhardson, Ian Hotham, Liam S. Sharninghausen, Robert A. Singer, Daniel W. Widlicka

2025Organic Process Research & Development7 citationsDOI

Abstract

The hydroxypicolinamide family of ligands has previously demonstrated utility in Cu-catalyzed C–N couplings and hydroxylation of heteroaryl halides. The application of these ligands has been extended to the coupling of ammonia with aryl bromides and iodides using the dimethoxy picolinamide scaffold ligand. By tailoring reaction conditions, Cu-DMPS provides high reactivity and selectivity toward amination over hydroxylation. Utilizing aqueous ammonia or anhydrous ammonia with K 3 PO 4 in MeOH provides robust conversion of bromides and iodides to the corresponding aryl amines. Additionally, this catalytic system gives efficient C–N couplings with simple primary amines by using the same general reaction conditions.

Topics & Concepts

HalideArylCatalysisAmmoniaChemistryCoupling (piping)Combinatorial chemistryOrganic chemistryMaterials scienceAlkylMetallurgyCatalytic Cross-Coupling ReactionsCatalytic C–H Functionalization MethodsSulfur-Based Synthesis Techniques
Cu-Catalyzed Coupling of Aryl Halides Utilizing Ammonia and Hydroxypicolinamide Ligands | Litcius