Transition Metal‐Mediated Functionalization of Isoxazoles: A Review

Abstract Isoxazoles are an important class of heterocycles with nitrogen and oxygen in a 1,2‐relationship. They find wide applications in synthetic organic chemistry and are part of several drug molecules. Since the last two decades, great progress has been achieved in the synthesis and functionalization of isoxazoles, in which transition metal catalysis played a pivotal role towards achieving this goal. In particular, the transition metal (TM)‐mediated site‐selective functionalizations of isoxazoles which retain the pharmacologically and synthetically valuable isoxazole skeleton, are highly appealing. This comprehensive review is solely dedicated to the TM‐mediated functionalization of isoxazoles, wherein we have included isoxazoles as directing groups (DG) for TM‐catalyzed C−H functionalization reactions, TM‐catalyzed direct C−H functionalization, along with cross‐coupling reactions of isoxazoles, TM‐catalyzed annulation reactions of isoxazoles and finally ring‐opening reactions of isoxazoles under TM‐catalysis are also discussed. Also, incorporated are discussions on reaction designs, their advantages and limitations, mechanistic details and challenges that need to be addressed to inspire synthetic organic and medicinal chemists to explore new reaction arenas and make use of this key scaffold.