Synergistic nitroreductase/vanadium catalysis enables chemoselective nitro reductions to anilines in the absence of hydrogen gas

Anilines are valuable synthons in pharmaceuticals and agrochemicals. These compounds are generally produced by chemocatalytic reduction of the corresponding nitrobenzene precursors. However, known synthetic methods often lack sufficient activity or selectivity, which results in low yields or the formation of a variety of undesired side products. We envisaged a biocatalytic approach as a promising general platform for selective and mild nitroarene reduction. Herein, we report using nitroreductases in combination with vanadium salts for the quantitative reduction of nitroaromatics to their corresponding anilines. Substrate scope studies were performed with fourteen nitrobenzene and four nitropyridine compounds. In one example, the reaction was intensified to 27 ​g/L substrate loading at 25 ​mL scale, where chemoselective reduction of the nitro group was obtained with full conversion and more than 93% selectivity toward aniline product (isolated in 82% yield). These conditions demonstrate the first general enzymatic method for the reduction of nitroaromatics to anilines.