Modular Cyano-fluoroalkylation of Unactivated Alkenes Enabled by Photoinduced Fe-LMCT Catalysis

Abstract

Abstract We describe the implementation of an iron catalyzed cyano-fluoroalkylation of unactivated alkenes that leverages inexpensive trifluoroacetic acid (CF3CO2H) and related carboxylic acids (CFnRCO2H) as radical fluoroalkyl sources, together with tosyl cyanide (TsCN) as a low-toxicity cyanation reagent. Notably, the mild and redox-neutral conditions of the method are compatible with a broad range of substrates, including alkenes containing biologically relevant motifs (40 examples, up to 83% yield). The resulting β-fluoroalkylated nitriles can be diversely derivatized to afford other valuable fluorinated sp3-rich architectures. Mechanistic studies have revealed the key role of a protonated bipyridine-based ligand in enhancing reaction efficiency.