Vinyl Sulfonates: A Click Function for Coupling-and-Decoupling Chemistry and their Applications

The term coupling‐and‐decoupling (CAD) chemistry refers to applications in which efficient bond formation and subsequent cleavage between two moieties is required. Within this context, the scope of the vinyl sulfonate (VSO) group as an efficient tool for CAD chemistry is reported. The coupling step relies on the click features of the Michael‐type addition of diverse nucleophiles to vinyl sulfonates as a valuable methodology. The feasibility of this strategy has been proved by the high yields obtained in mild conditions with model VSO derivatives. Cleavage of the resulting sulfonate adducts either through nucleophilic substitution with different nucleophiles (for alkyl VSO groups) or through hydrolysis (for both alkyl and aryl VSO) are successful strategies for the decoupling step, the former being the most promising, as the reaction proceeds under milder conditions with thiol nucleophiles. Moreover, the click VSO coupling chemistry proves to be orthogonal with the click CuAAC reaction, which enables the VSO‐CAD methodology for the preparation of hetero‐bifunctional clickable and cleavable linkers for double click modular strategies. The potential of the VSO‐CAD chemistry is demonstrated in two biologically relevant examples: the decoupling of sulfonates with glutathione (GSH) under conditions compatible with those of living systems; and the synthesis of homo‐ and heterogeneous multivalent glycosylated systems from 1‐thio and 1‐azido or 1‐azidoethyl sugar derivatives and bis‐vinyl sulfonates (homo systems) or alkynyl‐VSO bifunctional clickable‐cleavable linkers (hetero systems). As proof of concept, the cleavable character of these multivalent systems was demonstrated by using one of them as a reversible linker for the non‐covalent assembling and chemical decoupling of two model lectins.