Nickel-Catalyzed Alkyl–Alkyl Cross-Couplings of Fluorinated Secondary Electrophiles: A General Approach to the Synthesis of Compounds that Bear a Perfluoroalkyl Substituent**

Fluorinated organic molecules are of interest in fields ranging from medicinal chemistry to polymer science. Herein, we describe a mild, convenient, and versatile method for the synthesis of compounds that bear a perfluoroalkyl group attached to a tertiary carbon, via an alkyl–alkyl crosscoupling. Thus, a nickel catalyst derived from commercially available components (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 (e.g., alkyne, aryl iodide, carbamate, furan, ketone, nitrile, phosphonate, primary alkyl bromide, and primary alkyl tosylate) are 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 TEMPO inhibits cross-coupling under these conditions and that a TEMPO–electrophile adduct can be isolated.