Palladium-Catalyzed C(sp3)–H Bond Functionalization of Aliphatic Amines

Summary Methods that enable the practical and selective functionalization of traditionally unreactive aliphatic C–H bonds have synthetic applications in fields ranging from drug discovery to advanced materials. One of the major challenges is the development of strategically important reactions on aliphatic molecules containing synthetically useful functional groups. Aliphatic amines are central to the function of many biologically active molecules, as evidenced by their prevalence in a large number of pharmaceutical agents. Over the past decade, chemists have found ways to tailor the electronic and steric properties of directing functionalities and ligands to enable palladium-catalyzed C–H activation of aliphatic amine derivatives. Many of these methods have been successfully applied to the synthesis of pharmaceuticals and complex natural products. This review provides an overview of these methods and describes recent contributions, as well as the remaining challenges, in this emerging field.