3,3‐Difluoroallyl Sulfonium Salts: Practical and Bench‐Stable Reagents for Highly Regioselective gem‐Difluoroallylations

The site‐selective introduction of the difluoromethylene group into organic molecules has important applications in producing pharmaceuticals and agrochemicals. However, the general and efficient methods that can construct both C(sp2)−CF2R and C(sp3)−CF2R bonds remain challenging. Here, we disclose a new type of practical and bench‐stable difluoroalkylating reagent 3,3‐difluoroallyl sulfonium salt (DFAS) that can be practically prepared from inexpensive and bulk chemical feedstock 3,3,3‐trifluoropropene. This reagent allows highly regioselective gem‐difluoroallylation of various organozinc reagents, including aryl, primary, secondary, and tertiary alkyl zinc reagents, via copper catalysis under mild reaction conditions with high efficiency. The reaction can also be extended to a series of substituted DFASs. Application of the approach leads to the short synthesis of complex analogs, showing the prospect of DFASs in medicinal chemistry. A new type of bench‐stable yet highly reactive fluoroalkylating reagents, 3,3‐difluoroallyl sulfonium salts (DFASs), has been developed. The reaction of DFASs with aromatic and aliphatic zinc reagents via copper catalysis provides general and practical access to a wide range of versatile gem‐difluoroallylated compounds with high regioselectivity.