An “On-Cycle” Precatalyst Enables Room-Temperature Polyfluoroarylation Using Sensitive Boronic Acids

The use of fluorinated arylboronic acid building blocks in cross-coupling has remained challenging due to their acute base sensitivity. We report a general solution to this problem using a true catalytic intermediate, Pd(PAd₃)(p-FC₆H₄)Br, as a uniquely effective "on-cycle" precatalyst that allows Suzuki-Miyaura coupling to occur much faster than even the most severe protodeboronation side reactions. Control of boron speciation between the active acid and dormant ester forms was also found to play a critical role in balancing the rates of catalysis versus reagent decomposition. This method is compatible with any fluorination pattern, base-labile functional groups, and a range of bromo(hetero)arenes.