Photoinduced C(sp3)–Br bond Functionalization via Halogen Bond Interactions

Halogen bonding has emerged as a powerful tool in catalysis, where it provides a noncovalent platform for substrate preorganization and activation. In particular, its capacity to weaken and polarize the C–X bond of organic halides highlights its transformative potential under catalyst-free conditions. These advances position halogen bonding as a rapidly expanding frontier in noncovalent chemistry, bridging fundamental principles with innovative applications in synthesis, materials science, and beyond. In the present work, we report a joint computational and experimental investigation towards building halogen-bond interactions between DIPEA and the 2-bromo-2,2-difluoroethyl phenylcarboxylate, and its subsequent photoirradiation to generate a 2,2-difluoroethyl arylcarboxylate radical, which can subsequently react with sulfonyl acrylamides and 3-methyleneisoindolin-1-ones to form the corresponding difluorinated amides. Water is used as a key additive, which mediates hydrogen atom transfer by acting as a hydrogen radical shuttle. Key advantages of this protocol include mild reaction conditions, broad substrate compatibility, enhancement of yields in the presence of water, and the potential for further applications in the synthesis of pharmaceutically relevant molecules