Chemoenzymatic Synthesis of Sterically Hindered Biaryls by Suzuki Coupling and Vanadium Chloroperoxidase Catalyzed Halogenations

Abstract Halogenated biaryls are vital structural skeletons in bioactive products. In this study, an effective chemoenzymatic halogenation by vanadium‐dependent chloroperoxidase from Curvularia inaeqaelis ( Ci VCPO) enabled the transformation of freely rotating biaryl bonds to sterically hindered axis. The yields were up to 84 % for the tribrominated biaryl products and up to 65 % when isolated. Furthermore, a one‐pot, two‐step chemoenzymatic strategy by incorporating transition metal catalyzed Suzuki coupling and the chemoenzymatic halogenation in aqueous phase were described. This strategy demonstrates a simplified one‐pot reaction sequence with organometallic and biocatalytic procedures under economical and environmentally beneficial conditions that may inspire further research on synthesis of sterically hindered biaryls.