Recent Advances and Prospect in Stereospecific Sulfur(VI) Fluoride Exchange Chemistry

Sulfur(VI) fluoride exchange (SuFEx) has emerged as a powerful click chemistry platform for covalent bond formation, with broad applications in drug discovery, polymer science, and bioconjugation. Among the diverse SuFEx linkers developed in recent years, sulfonimidoyl fluorides (RN=S(O)F) have gained prominence due to their tunable electrophilicity, multifunctional modifiable sites, and the presence of chiral sulfur(VI) centers. This reagent exhibits exceptional reactivity in stereospecific SuFEx transformations, offering not only an efficient strategy for the synthesis of enantioenriched sulfur compounds but also a versatile foundation for covalent drug discovery and chemical probe development. This review systematically summarizes recent advances in sulfonimidoyl fluoride chemistry, with an emphasis on the construction of chiral S(VI) centers and stereocontrolled SuFEx reactions. Despite the limited literature in this nascent field, key breakthroughs and discuss future research directions, is consolidated providing forward‐looking perspectives to stimulate further progress in stereospecific SuFEx chemistry.