Tetrafluoroethylene (-CF2CF2-) is a privileged motif in materials and medicinal chemistry. However, a highly modular and synthetically convenient method for constructing the CF2CF2 linkage remains elusive. Here, we report an unprecedented copper-catalyzed, bench-friendly difluorocarbene elongation platform that converts BrCF2CO2K, silyl enol ethers, and secondary propargyl sulfonates into tetrafluoroalkylated allenes in a single operation. Simply tuning the difluorocarbene stoichiometry switches selectivity to the corresponding monodifluoromethylene (CF2) incorporation products. The method is modular (no preformed fluorinated building blocks are required), operationally simple (all reagents are commercially available or easily prepared), highly selective (controllable formation of bis- or mono-CF2-containing products), and tolerant of diverse functional groups, including those found in drug-like scaffolds. The products serve as versatile linchpins for downstream transformations, opening expedient routes to advanced materials and modern drug discovery.
Huang et al. (Wed,) studied this question.