Chapter 8: C–H Activation Approaches to Molecules

C–H functionalisation reactions that directly forge C–C and C–X bonds have garnered considerable interest over the past years due to the prevalence of aromatic moieties and heteroatoms in pharmaceuticals and natural products. Traditional cross-coupling tactics rely on strategically installed metal groups and, as such, the transformation of these functional groups underpins conventional synthetic strategy. Direct C–H bond functionalisation is an attractive tool for organic chemists, potentially affording significant atom efficiencies and expediting the synthesis of complex molecules through new ‘topologically obvious’ disconnections. Whilst an extremely appealing concept, a significant challenge is presented by the ubiquitous, and often unreactive, nature of C–H bonds in organic molecules. Recent advances in the field have focused on the development of new catalyst systems that are both highly reactive and predictably selective, which is essential to significantly increase the efficiency with which carbon frameworks can be constructed and functionalised. These recently developed C–H functionalisation methods have the potential to streamline synthesis, allow access to novel heterocycles and enable late-stage diversification of biologically active entities. As such, they can both accelerate the speed with which structure–activity relationships are generated and the efficiency by which drug targets can be produced. This chapter provides an overview of C–H functionalisation strategies, and in particular, their application to the synthesis of pharmaceutical targets.