Copper-Catalyzed Cross-Coupling of Malonates with Aryl Halides Using Hydroxypicolinamide Ligands

Abstract Cu-catalyzed cross-coupling of aryl halides and malonates using hydroxypicolinamide ligands to furnish the corresponding aryl malonates is disclosed herein. Malonates are commonly coupled with aryl halides via Pd catalysis, with a few reports of classic Hurtley-type Cu-mediated couplings. The Cu-MPBS system, originally designed for C–N coupling, has been further developed for the Cu-catalyzed coupling of diethyl malonate with aryl bromides and less precedented aryl chlorides. Our hydroxypicolinamide ligand scaffold promotes the Hurtley-type coupling of diethyl malonate under mild conditions for aryl bromides (20–40 °C) and aryl chlorides (60–80 °C) with low Cu loading (2–4 mol %). Reaction conditions are compatible with a wide variety of functional groups and heterocycles to provide the desired malonate. Furthermore, we demonstrated a telescoped process to the α-aryl ester simply by heating to drive subsequent decarboxylation.