Main group metal-mediated strategies for C–H and C–F bond activation and functionalisation of fluoroarenes

With fluoroaromatic compounds increasingly employed as scaffolds in agrochemicals and active pharmaceutical ingredients, the development of methods which facilitate regioselective functionalisation of their C–H and C–F bonds is a frontier of modern synthesis. Along with classical lithiation and nucleophilic aromatic substitution protocols, the vast majority of research efforts have focused on transition metal-mediated transformations enabled by the redox versatilities of these systems. Breaking new ground in this area, recent advances in main group metal chemistry have delineated unique ways in which s-block, Al, Ga and Zn metal complexes can activate this important type of fluorinated molecule. Underpinned by chemical cooperativity, these advances include either the use of heterobimetallic complexes where the combined effect of two metals within a single ligand set enables regioselective low polarity C–H metalation; or the use of novel low valent main group metal complexes supported by special stabilising ligands to induce C–F bond activations. Merging these two different approaches, this Perspective provides an overview of the emerging concept of main-group metal mediated C–H/C–F functionalisation of fluoroarenes. Showcasing the untapped potential that these systems can offer in these processes; focus is placed on how special chemical cooperation is established and how the trapping of key reaction intermediates can inform mechanistic understanding.