Construction of a Chiral Click Chemistry Platform via Enantioselective F/Cl Exchange at S(VI) Centers

Sulfonimidoyl fluorides have emerged as versatile click linkers, where the construction of sulfur-centered chirality plays a pivotal role in chiral recognition, stereoselective binding, and spatial interactions. However, the enantioselective formation of S(VI)-F bonds faces a significant challenge due to facile racemization from low activation barriers. Herein, we introduce inorganic sodium bifluoride (NaHF₂), which enables a three-dimensional hydrogen-bonding network to promote stereoinversion of the S-Cl bond via dynamic kinetic asymmetric fluorination, thereby delivering excellent yields and enantioselectivities. Mechanistic studies reveal that a robust hydrogen-bonding catalytic complex with the HF₂^- anion is essential for enantiocontrol. This strategy paves the way for chiral click bioconjugation.