title: Nickel-Catalyzed Alkyl-Alkyl Cross-Couplings of Fluorinated Secondary Electrophiles: A General Approach to the Synthesis of Compounds having a Perfluoroalkyl Substituent.
abstract: Fluorinated organic molecules are of interest in fields ranging from medicinal chemistry to polymer science. Described herein is a mild, convenient, and versatile method for the synthesis of compounds bearing a perfluoroalkyl group attached to a tertiary carbon atom by using an alkyl-alkyl cross-coupling. A nickel catalyst derived from NiCl2 ⋅glyme and a pybox ligand achieves the coupling of a wide range of fluorinated alkyl halides with alkylzinc reagents at room temperature. A broad array of functional groups is compatible with the reaction conditions, and highly selective couplings can be achieved on the basis of differing levels of fluorination. A mechanistic investigation has established that the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) inhibits cross-coupling under these conditions and that a TEMPO-electrophile adduct can be isolated.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 (USA).
authors.forename: Yufan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 (USA). gcfu@caltech.edu.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Fu
mesh_terms: D002384:Catalysis; D054879:Halogenation; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry*
chemical_list: D009532:Nickel; D015032:Zinc
keywords: cross-coupling; fluorine; homogeneous catalysis; nickel; zinc