Copper-Catalyzed Highly Enantioselective Difluoroalkylation of Secondary Propargyl Sulfonates with Difluoroenoxysilanes

Summary Despite the impressive progress recently made in transition-metal-catalyzed fluoroalkylation, the related asymmetric fluoroalkylation remains a challenging topic. Here, we report a copper-catalyzed highly enantioselective difluoroalkylation of secondary propargyl sulfonates using difluoroenoxysilanes. The reaction proceeds under mild reaction conditions with Cu(I)/PyBox as the catalyst. The advantages of this method include high efficiency, high enantioselectivity (enantiomeric ratio up to 99:1), and excellent functional-group tolerance. The resulting chiral propargylic α,α-difluoroketones can be transformed into enantiomerically enriched propargyl difluoromethylated compounds, providing a good platform for accessing a wide range of chiral difluoromethylated compounds that are of great interest in medicinal chemistry and materials science.