Functionalizing traditionally inert carbon–hydrogen bonds represents a powerful transformation in organic synthesis, providing new entries to valuable structural motifs and improving the overall synthetic efficiency. C–H bond activation, however, often necessitates harsh reaction conditions that result in functional group incompatibilities and limited substrate scope. An understanding of the reaction mechanism and rational design of experimental conditions have led to significant improvement in both selectivity and applicability. This critical review summarizes and discusses endeavours towards the development of mild C–H activation methods and wishes to trigger more research towards this goal. In addition, we examine select examples in complex natural product synthesis to demonstrate the synthetic utility of mild C–H functionalization (84 references).

C–H Activation reactions that proceed under mild conditions are more attractive for applications in complex molecule synthesis. Mild C–H transformations reported since 2011 are reviewed and the different concepts and strategies that have enabled their mildness are discussed.

Visible-light-mediated energy transfer has experienced a renaissance in organic synthesis within the last ten years. This tutorial review covers its diverse applications, along with the (photo)physical fundamentals required to rationalize and predict those processes.