ReviewRSC advances2026
The evolution of click chemistry: from classical reactions to next-generation platforms.
Review in RSC advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
2 authors.
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Abstract
Click chemistry has transformed modern synthetic chemistry by providing efficient, selective, and modular strategies for constructing complex molecular structures. Since its introduction, the field has expanded from classical synthetic reactions to bioorthogonal and next-generation click platforms, broadening its applications across organic synthesis, polymer science, materials engineering, chemical biology, medicinal chemistry, and biomedicine. This review summarizes the evolution of click chemistry across three major generations. The first generation includes classical reactions such as copper-catalyzed azide-alkyne cycloaddition (CuAAC), thiol-ene, thiol-yne, thiol-ene Michael addition (TEMA), Diels-Alder (DA) cycloadditions, and nucleophilic ring-opening reactions. The second generation focuses on bioorthogonal transformations, including Strain-Promoted Alkyne-Azide Cycloaddition (SPAAC), Strain-Promoted Alkyne-Nitrone Cycloaddition (SPANC), and inverse electron-demand Diels-Alder (IEDDA) reactions, which enable selective chemical modification in living systems. The third generation encompasses emerging platforms such as sulfur(vi) fluoride exchange (SuFEx) and phosphorus(v) fluoride exchange (PFEx), which provide enhanced structural tunability, external control, and broader application potential. For each reaction class, the review discusses fundamental mechanisms, key advantages, limitations, and representative applications, highlighting how click chemistry has evolved from efficient bond formation toward increasingly precise chemical control in biological and materials environments.
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Registered trials
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