CuOTf(Tol)1/2-Catalyzed O-Trifluoroethylation of Alcohols with 2,2,2-Trifluorodiazoethane

Trifluoroethyl groups are important in medicinal chemistry since they can impart desirable properties, such as enhanced lipophilicity, metabolic stability, or binding affinity. A practical and scalable protocol has been developed for O-trifluoroethylation of alcohols with 2,2,2-trifluorodiazoethane using Cu(OTf)(Tol)1/2 catalyst under mild conditions. This novel approach demonstrated high reactivity and broad substrate scope toward a diverse range of alcohols, ranging from fused and bridged ring systems, linear alcohols, to even sugar motifs, which makes the protocol valuable for medicinal chemistry, material science, and other areas where the introduction of trifluoroethyl groups would be beneficial.