Synthesis of Functionalised Aryl and Heteroaryl Compounds via Ligand-Free Metal-Catalysed Kumada and Ullmann Cross Coupling Reactions in Unconventional Reaction Media

Metal-catalysed organic reactions are among the most frequently encountered methodologies in the synthetic chemist’s toolbox, providing powerful instruments to achieve high functionalised organic products. A new challenge of this century is to perform these reactions in inexpensive, green and biorenewable reaction media, in place of volatile and harsh organic solvent (VOCs) [1,2]. Deep Eutectic Solvents (DESs) are a new generation of green and unconventional solvents, generally composed of two or three safe and inexpensive components, which are able to engage in hydrogen-bond interactions with each other to form an eutectic mixture with a melting point much lower than that of either of the individual components [3]. Palladium-catalysed Kumada [4,5] and copper-catalysed Ullmann-type reactions [6,7,8] allow to synthesise functionalised aryl and heteroaryl compounds starting from aryl halides and organometallic reagents as nucleophiles in Kumada reaction and amines in Ullmann reaction. These reactions are usually carried out in VOCs (e.g. THF, toluene), at high temperature and generally several expensive ligands are employed. In this communication we report two environmentally friendly synthetic methodologies useful to prepare functionalised aryl and heteroaryl compounds. Key features of this work are (a) the use of water and cheap and reusable eutectic mixtures as reaction media, (b) the absence of ligands and (c) mild reaction condition (under air and moderate heating), with the desired products isolated in high yields (up to > 98%).