Late‐Stage Functionalization by Transition Metal‐Catalyzed C H Functionalization

Late-stage diversification of complex molecules is extremely important in the drug design process, allowing rapid access to a myriad of leads' congeners while avoiding de novo synthesis. The CH activation approach via metal catalysis is a unique way of achieving this challenging goal. Indeed, the native functional groups that are commonly found on drug-like molecules can frequently be used as a directing group to enhance regioselective metalation events. Once a catalytic system has been designed to activate a specific CH bond, various functionalizations can be envisaged, thus further expanding the chemical space. Given the significant advances in Late Stage Functionalization via CH activation, this chapter outlines key strategies for the late-stage diversification of aromatic and aliphatic compounds. To give readers an overview of the potential of LSF, each section is organized by the type of new bond formed and focuses on recent examples. Mechanistic considerations guide the reader through the fundamental aspects of a given transformation, such as regioselectivity control. Given the maturity of the LSF field and the large number of publications, this chapter does not claim to be exhaustive but rather focuses on the key conceptual strategies employed by the authors to elegantly decorate complex molecules.