To be or not to be metal-free: trends and advances in coupling chemistries
Coupling reactions have been part of several extensive studies in order to develop innovative and greener protocols that can generate a wide range of compounds with applications in pharmaceuticals, agrochemicals and biologically active compounds. Metal-free couplings are an important and increasingly trendy field that has attracted a significant deal of interest in recent years, generating a lot of controversy on the issue of whether metal free is really free. Aside from focusing on such a controversial topic itself, this contribution aims to provide a brief introduction on coupling chemistry to point out the transition of this technology from metal-catalyzed to metal-free. This is followed by a range of key selected synthetically useful metal-free processes and a brief commentary on the current debate of whether metal-free reactions are really metal-free and the required experiments for a full understanding of a metal-free coupling process.