Integrating Enzymes with Photoredox Catalysis for Conversion of Nitriles into Fluorinated Products

Abstract Fluorinated molecules are widely used as pharmaceuticals, agrochemicals, and as various functional materials. Traditional synthetic methods for introducing fluorine substituents into organic molecules involve deleterious chemicals and lack selectivity. Enzymes have evolved in nature which can halogenate a diverse range of substrates with high selectivity under aqueous conditions, using benign inorganic halides as the halogen source. Although there are many halogenase enzymes that can chlorinate or brominate diverse substrates, only one fluorinase enzyme has been discovered to date that produces a single fluorinated adenosine derivative in nature. Herein, we complement the lack of biocatalytic fluorination protocols and address the need for cleaner and more selective fluorination methods by merging chemo and biocatalysis to selectively fluorinate compounds in a single integrated reaction. Our approach relies on combining nitrilase enzymes with photoredox catalysis to transform cheap and abundant organonitrile compounds into highly sought‐after fluorinated, trifluoromethylated, and perfluoroalkylated compounds.