Sheng-Yu Chen, Xueqing Wang, Luning Tang, Yibin Wang, Yiyi Chen, Ming Chen
A palladium-catalyzed C3- ipso -didefluoroannulation of allylic gem -difluorides with salicylic acids has been developed, proceeding under mild conditions with broad functional group tolerance and enabling late-stage functionalization of bioactive scaffolds. Mechanistic studies reveal a key monofluoroalkene intermediate that undergoes two successive Pd(0)/Pd(II) cycles involving C–F activation and allylic C–O oxidative addition with a formal 1,3-ether migration, thereby reversing both catalyst- and nucleophile-controlled regioselectivities. This strategy not only expands the synthetic utility of allylic gem -difluorides but also establishes a new paradigm for regioselective C–F bond functionalization in transition metal catalysis.