1,2,4‐Oxadiazol‐5(4 H )‐Ones: Versatile Building Blocks in Synthetic Chemistry

Abstract The rapid construction of densely functionalized molecules through the exploration of versatile multitasking building blocks holds significant synthetic potential for pharmaceuticals, agrochemicals, and advanced materials. Among these, 1,2,4‐oxadiazol‐5(4 H )‐ones have emerged not only as key scaffolds in biologically active molecules but also as highly adaptable synthons, enabling diverse synthetic transformations for the concise and selective assembly of functionalized architectures. Over the past decades, the reactivity profile of 1,2,4‐oxadiazol‐5(4 H )‐ones has been greatly expanded, facilitating their use as O‐ or N‐nucleophiles, nitrogen sources for direct C–H functionalization, directing groups, and internal oxidizing directing groups. These attributes allow for the efficient synthesis of diverse heterocyclic systems and complex molecular frameworks under mild and sustainable conditions. This review comprehensively summarizes recent advances in the synthetic applications of 1,2,4‐oxadiazol‐5(4 H )‐ones, covering their roles as bifunctional reagents, coupling partners, and redox‐active auxiliaries in transition‐metal‐catalyzed and metal‐free transformations. We also provide a critical outlook on future directions, including enantioselective catalysis, photoredox and electrochemical applications, and the integration of oxadiazolones in the synthesis of bioactive molecules and functional materials. It is anticipated that this review will inspire further innovation in the design and application of multitasking building blocks in synthetic chemistry.