Difluorocarbene as a Dual C ₁ /CF ₂ Source for HCF ₂ S Heterocycle Synthesis

This study presents a strategy utilizing difluorocarbene as a dual C 1 /CF 2 source for the efficient synthesis of HCF 2 S-substituted six-membered aromatic heterocycles. The in situ generation of thiocarbonyl fluoride (S═CF 2 ) from the reaction of readily available difluorocarbene reagent Ph 3 P + CF 2 CO 2 – (PDFA) with elemental sulfur enables the simultaneous cyclization and difluoromethylthiolation of substrates containing vicinal nucleophilic groups (amide or carboxyl) and amines. This method provides rapid access to quinazolinone and benzoxazinone scaffolds bearing the biologically relevant difluoromethylthio group under mild conditions, demonstrating a broad substrate scope and functional group compatibility. The work highlights the versatility of difluorocarbene in constructing valuable fluorinated heterocycles with potential applications in medicinal and agrochemical chemistry.