Desulfonative Suzuki–Miyaura Coupling of Sulfonyl Fluorides

Abstract Sulfonyl fluorides have emerged as powerful “click” electrophiles to access sulfonylated derivatives. Yet, they are relatively inert towards C−C bond forming transformations, notably under transition‐metal catalysis. Here, we describe conditions under which aryl sulfonyl fluorides act as electrophiles for the Pd‐catalyzed Suzuki–Miyaura cross‐coupling. This desulfonative cross‐coupling occurs selectively in the absence of base and, unusually, even in the presence of strong acids. Divergent one‐step syntheses of two analogues of bioactive compounds showcase the expanded reactivity of sulfonyl fluorides to encompass both S−Nu and C−C bond formation. Mechanistic experiments and DFT calculations suggest oxidative addition occurs at the C−S bond followed by desulfonation to form a Pd‐F intermediate that facilitates transmetalation.