Pd-Catalyzed Regioselective Activation of <i>gem</i> -Difluorinated Spiro[2.2]pentanes: An Approach to 2-Fluorinated 1,3-Dienes

An efficient palladium-catalyzed regioselective activation of gem -difluorinated spiro[2.2]pentanes for constructing 2-fluorinated 1,3-dienes has been developed. A series of multisubstituted 2-fluoro-1,3-dienes were synthesized in moderate to excellent yields. The generated fluorinated conjugated dienes were employed as precursors in Diels–Alder reactions to construct fluoro-substituted cyclohexene scaffolds, which are ubiquitous motifs in drug molecules. This work reports the first palladium-catalyzed, regioselective ring-opening functionalization of gem -difluorospiropentanes, induced by C–C bond cleavage and followed by sequential β-C/β-F eliminations. This breakthrough significantly expands the utility of gem -difluoro-substituted small-ring compounds as synthetic precursors, thereby unlocking the potential of gem -difluorospiro[2.2]pentanes as versatile synthons in synthetic chemistry.