Enantioselective Cu-Catalyzed Nucleophilic Addition of Fluorinated Reagents: C–C Bond Formation for the Synthesis of Chiral Vicinal Difluorides
Huaxin Lin, Wei Jiao, Zhiwei Chen, Jian Han, Dongmei Fang, Min Wang, Jian Liao
Abstract
Herein we described the first enantioselective Cu/sulfoxide phosphine (SOP) complex catalyzed nucleophilic addition of fluorinated enolates to gem-difluoroalkenes. The enantioenriched vicinal difluorides, containing a chiral tertiary fluoride and a fluoroalkene, were successfully afforded via C–C bond formation in good yields (up to 94% yield), high Z/E-selectivity (5:1 → 50:1 for Z-isomer), and excellent enantioselectivities (up to 98.5:1.5 er). Utility of this approach was demonstrated by modification of complex biologically active compounds.
Topics & Concepts
ChemistryEnantioselective synthesisVicinalNucleophileDifluorideCatalysisSulfoxideSelectivityReagentYield (engineering)PhosphineMedicinal chemistryCombinatorial chemistryOrganic chemistryMetallurgyMaterials scienceFluorine in Organic ChemistryCatalytic C–H Functionalization MethodsAsymmetric Synthesis and Catalysis