K₂S₂O₈-Powered One-Pot Multi-Bond Formations

Potassium persulfate (K2S2O8) has recently become an important oxidizing reagent for designing one-pot reactions that form multiple bonds in a single synthetic operation. Its ability to generate reactive radical species under mild conditions allows the efficient assembly of C-C and C-heteroatom (N, O, S, Se, P, halo) linkages without the need for transition metals or harsh reaction environments. Owing to these features, K2S2O8 has been incorporated into numerous streamlined protocols that emphasize step economy and sustainability. Recent studies have demonstrated its value in sequential alkylation-cyclization processes, selective chalcogenation and thiocyanation reactions, and the construction of functionalized xanthene and indenone cores. These methodologies often show impressive levels of chemo-, regio-, and stereocontrol, reflecting the reagent’s versatility and predictable reactivity. Combining K2S2O8 with modern catalytic approaches, such as visible-light photoredox catalysis, has further expanded its scope. Such hybrid systems frequently operate under even milder conditions, tolerate a wider range of substrates, and enable rapid access to molecular architectures relevant to medicinal chemistry, natural product synthesis, and functional material development. Radical cascade and relay strategies initiated by K2S2O8 have also proven especially powerful for building complex frameworks in a concise manner. This review compiles and discusses recent contributions reported from 2021 onward, focusing on one-pot, multi- bond-forming reactions that rely on K2S2O8 as the key oxidant. Emphasis is placed on synthetic utility, substrate breadth, mechanistic proposals, and the broader impact of these advances on sustainable organic synthesis. Collectively, these developments illustrate the growing importance of K2S2O8 in enabling efficient, selective, and environmentally responsible bond-forming strategies.