Electrophilic glycoluril-based reagents for atom-economic thiocyanation and selenocyanation of (hetero)arenes

Abstract

Two electrophilic glycoluril-based N-XCN reagents (X = S, Se) were developed for introducing SCN/SeCN groups into aromatic substrates, including the late-stage modification of bioactive molecules. Their application produces minimal waste, enables simple purification, and offers potential for reagent regeneration. Additionally, their compatibility with green solvents and flow technology was demonstrated. The sustainability of the process was evaluated using green metrics and Ecoscale values, emphasizing the complementary roles of the reagents and solvent recovery in enhancing atom economy and reducing waste.