Advances in sulfonyl guanidine synthesis: mechanistic insights and future perspectives

Organic compounds containing guanidine moieties are ubiquitous in nature and exhibit significant potential in the biological and pharmaceutical industries. Recently, the synthesis of sulfonyl guanidines has attracted the attention of chemists due to their wide-ranging applications as antibacterials, anticonvulsants, and potent therapeutic agents for the treatment of thrombosis and cardiovascular disorders. Beyond their pharmaceutical applications, guanidine derivatives can also serve as organoligands, catalysts, superbases, and superpotent sweeteners. Driven by their significance and utility, chemists have devoted themselves to the development of efficient methods for the synthesis of sulfonyl guanidines. Several sulfonyl precursors, such as sulfonamides, sulfonyl azides, N,N-dibromoaryl sulfonamides, arylsulfonyl isocyanates, sulfuryl fluoride, bromamine-T, etc., efficiently deliver sulfonamide-protected guanidines. This review integrates recent synthetic advances with a critical evaluation of the methodologies and synthetic challenges, emphasizing mechanistic insights, major strengths and limitations, industrial viability, sustainability, and future scope. This article is expected to serve as a valuable tool for strengthening next-generation sulfonyl guanidine chemistry. Additionally, the perspectives presented herein are anticipated to stimulate future research and innovation in the synthesis and application of sulfonyl guanidines across diverse areas, such as organic synthesis, materials science, medicinal chemistry, and pharmaceutical sciences. Despite significant progress, sulfonyl guanidines remain underexplored as chiral organocatalysts, supramolecular ligands, catalyst-coordinating ligands, and molecular recognition agents. Future advances are expected to propel sulfonyl guanidines beyond their current role as valuable synthetic intermediates into multifunctional molecular platforms with far-reaching scientific and technological applications.