Efficient Synthesis of (S)-Aromatic Epoxides by Coupling Mechanochemical Synthesis and Biocatalysis Technology

(S)-aromatic epoxides are of great importance in the production of pharmaceuticals and biologically active natural products. Consequently, developing efficient, ecofriendly, and economical methods for production of (S)-aromatic epoxides continues to be of tremendous interest in organic synthesis. Herein, we report a novel protocol for the efficient synthesis of (S)-aromatic epoxides by coupling mechanochemical synthesis and biocatalysis from commercially available and cheap materials. The first step of the process is the halogenation of aromatic ketones with N-halosuccinimides (NXS) under ball-milling conditions to form alpha-haloaromatic ketones. This is followed by a one-pot asymmetric bioreduction-cyclization sequence affording the various (S)-aromatic epoxides in good yields, which are pure enough without further purification. Compared to the traditional chemical approaches, this mechano-biocatalytic protocol has prominent advantages, including inexpensive starting materials, short reaction time, simplicity of operation, environmental benignity, broad substrate spectrum, good to excellent enantioselectivities, and easy isolation of products.