Nickel‐Catalyzed Alkyl–Alkyl Cross‐Couplings of Fluorinated Secondary Electrophiles: A General Approach to the Synthesis of Compounds having a Perfluoroalkyl Substituent

Abstract

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 NiCl 2 ⋅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.