Synthesis of Enantioenriched Sulfoxides by an Oxidation‐Reduction Enzymatic Cascade

Abstract Chiral sulfoxides are versatile synthons and have gained a particular interest in asymmetric synthesis of active pharmaceutical and agrochemical ingredients. Herein, a linear oxidation–reduction bienzymatic cascade to synthesize chiral sulfoxides is reported. The extraordinarily stable and active vanadium‐dependent chloroperoxidase from Curvularia inaequalis ( Ci VCPO) was used to oxidize sulfides into racemic sulfoxides, which were then converted to chiral sulfoxides by highly enantioselective methionine sulfoxide reductase A (MsrA) and B (MsrB) by kinetic resolution, respectively. The combinatorial cascade gave a broad range of structurally diverse sulfoxides with excellent optical purity (>99 % ee) with complementary chirality. The enzymatic cascade requires no NAD(P)H recycling, representing a facile method for chiral sulfoxide synthesis. Particularly, the envisioned enzymatic cascade not only allows Ci VCPO to gain relevance in chiral sulfoxide synthesis, but also provides a powerful approach for ( S )‐sulfoxide synthesis; the latter case is significantly unexplored for heme‐dependent peroxidases and peroxygenases.