Pd-Catalyzed Difluoroalkylation\nof Alkenes Using Chlorodifluoroalkanes

The gem-difluoromethylene unit (−CF<sub>2</sub>−)\nplays a pivotal role in expanding chemical space due to its ability\nto induce unique molecular geometries and physicochemical properties,\nmaking it highly desirable in the development of pharmaceuticals,\nagrochemicals, and advanced materials. Despite their significance,\nefficient and versatile methods for incorporating −CF<sub>2</sub>– groups into organic molecules remain challenging. We describe\na palladium-catalyzed difluoroalkylation of alkenes via a formal Mizoroki–Heck\nreaction, providing a straightforward, cost-effective, and atom-economic\nroute to synthesize a diverse array of RCF<sub>2</sub>-alkenes from\nreadily available alkenes and chlorodifluoroalkanes. This method facilitates\nthe incorporation of gem-difluoromethylene groups into complex molecules\nunder mild conditions and demonstrates remarkable functional group\ntolerance, enabling late-stage functionalization. Preliminary mechanistic\nstudies support a hybrid palladium-catalyzed radical-polar crossover\nmechanism. This approach offers an efficient and selective means to\nincorporate difluoromethylene units, broadening opportunities for\nthe design of bioactive molecules and advanced materials and advancing\nsynthetic strategies for a variety of applications.