Pd-Catalyzed Regioselective Activation of gem-Difluorinated Spiro[2.2]pentanes: An Approach to 2-Fluorinated
Ying Tang1, Yong-Yu Jiang1, Wen-Mei Luo1
1School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, Guangdong 529020, P. R. China.
Abstract:
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.
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