Small-Molecule-Catalyzed Late-Stage Aromatic Halogenation

Abstract Halogen atoms are widely present in pharmaceuticals and natural products. Late-stage C–H halogenation of complex arenes can modulate molecular properties, metabolic stability, and biological activity and can provide sites for further derivatization. This Review summarizes recent advances in small-molecule-catalyzed late-stage C–H halogenation of complex arenes. The discussion is organized first by the mode of activation of the halogenating reagent and then by catalyst type. The reaction characteristics, catalyst design, substrate scope, and catalytic mechanisms of different catalytic systems are classified and compared. Furthermore, current challenges and future directions are also discussed, offering insights into the application of late-stage halogenation to complex molecules.