Chromium(II)-Catalyzed Stereoselective Cross-Electrophile Coupling of Geminal Difluoroalkenes with Aliphatic Halides

Abstract

We report here an effective, mild and practical approach to stereoselective cross-electrophile coupling of difluoroalkenes with alkyl halides by cost-effective chromium catalysis. This reaction was promoted by inexpensive CrCl2 combining with bipyridine ligand and manganese as the reductant, enabling the achievement of the reductive coupling of geminal difluoroalkenes with primary, secondary and tertiary alkyl halides at ambient temperature. It provides a valuable and scalable approach to form tri-substituted Z-fluoroalkylalkenes with good compatibility to a range of important functional groups. Preliminary mechanistic studies indicate that the coupling reaction is initiated by forming alkyl radical by addition to alkene and combining with Cr(II) or by coordination with Cr(II) and carbometallation of difluoroalkenes in giving (alkyl)Cr species, which converts to Z-alkylated fluoroalkene motifs in a stereoselective manner by elimination of beta-fluoride atoms.