Micelle-enabled bromination of α-oxo ketene dithioacetals: mild and scalable approach via enzymatic catalysis

Abstract

The bromination of α-oxo ketene dithioacetals using KBr/H₂O₂, catalyzed by Curvularia inaequalis vanadium chloroperoxidase (CiVCPO), has been successfully demonstrated. A comparative study of enzymatic processes “on water” versus “in water”, using 2 wt% of the surfactant TPGS-750-M revealed that the in-water protocol not only provides higher yields but also accommodates a broader substrate scope. This bromination method in an aqueous micellar medium enabled the preparation of brominated α-oxo ketene dithioacetals in fair to excellent yields (23 examples). In the micellar system, the substrate concentration was increased up to 50 mM, and the amounts of the brominating agents KBr and H₂O₂ were reduced to approximately 2.0 equivalents without compromising efficiency. Notably, this process allows for the gram-scale preparation of brominated α-oxo ketene dithioacetals in high yields. Key advantages of this method include its benign and eco-friendly nature, the use of water as a green solvent, and its potential for large-scale production of brominated α-oxo ketene dithioacetals.