Copper-Catalyzed Regio- and Enantioselective Hydroboration of Difluoroalkyl-Substituted Internal Alkenes

Catalytic asymmetric hydroboration of fluoroalkyl-substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl-substituted alkenes without fluorine elimination has been a long-standing challenge in this field. Herein, a copper-catalyzed hydroboration of difluoroalkyl-substituted internal alkenes with high levels of regio- and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom-economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated. A copper-catalyzed regio- and enantioselective hydroboration of difluoroalkyl-substituted internal alkenes without fluorine elimination is realized, thus enabling practical and atom-economic access to a broad scope of chiral secondary boronates containing the valuable difluoromethylene motifs.image

Automated summary

In this study, a copper-catalyzed hydroboration of difluoroalkyl-substituted internal alkenes with high regio- and enantioselectivities is reported. The use of a native carbonyl directing group, copper hydride system, and bisphosphine ligand plays a crucial role in suppressing fluoride elimination and achieving the desired selective hydroboration. This atom-economic protocol provides a practical and efficient synthetic platform for the preparation of chiral secondary boronates containing difluoromethylene motifs.