Cu-Catalyzed Couplings of Heteroaryl Primary Amines and (Hetero)aryl Bromides with 6‑Hydroxypicolinamide Ligands

A family of 6-hydroxypicolinamide ligands have been identified as effective supporting ligands for Cu-catalyzed couplings of heteroaryl bromides and chlorides with heteroaryl primary amines. The C–N couplings are carried out at 80–120°C in DMSO or sulfolane using K2CO3 or K3PO4 as the base with 2–10 mol % CuI and supporting ligand. The strength of the base was found to have an impact on the chemoselectivity and rate. The use of K2CO3 as the base enabled selective C–N coupling of aryl bromides over aryl chlorides with 2–5 mol % Cu at 80–120 °C. With K3PO4 as the base, aryl chlorides are capable of undergoing C–N coupling, though 5–10 mol % Cu is required at 120–130 °C. Members of the ligand family are straightforward to prepare in one step from 6-hydroxypicolinic acid and the corresponding anilines.