Late-stage meta-C-H alkylation of pharmaceuticals to modulate biological properties and expedite molecular optimisation in a single step.

Catalysed C-H activation has emerged as a transformative platform for molecular synthesis and provides new opportunities in drug discovery by late-stage functionalisation (LSF) of complex molecules. Notably, small aliphatic motifs have gained significant interest in medicinal chemistry for their beneficial properties and applications as sp-rich functional group bioisosteres. In this context, we disclose a versatile strategy with broad applicability for the ruthenium-catalysed late-stage meta-C(sp)-H alkylation of pharmaceuticals.

Late-stage C-H functionalization offers new opportunities in drug discovery.

Over the past decade, the landscape of molecular synthesis has gained major impetus by the introduction of late-stage functionalization (LSF) methodologies. C-H functionalization approaches, particularly, set the stage for new retrosynthetic disconnections, while leading to improvements in resource economy. A variety of innovative techniques have been successfully applied to the C-H diversification of pharmaceuticals, and these key developments have enabled medicinal chemists to integrate LSF strategies in their drug discovery programmes.

When metal-catalyzed C-H functionalization meets visible-light photocatalysis.

While aiming at sustainable organic synthesis, over the last decade particular attention has been focused on two modern fields, C-H bond activation, and visible-light-induced photocatalysis. Couplings through C-H bond activation involve the use of non-prefunctionalized substrates that are directly converted into more complex molecules, without the need of a previous functionalization, thus considerably reduce waste generation and a number of synthetic steps. In parallel, transformations involving photoredox catalysis promote radical reactions in the absence of radical initiators.