Biocatalytic Thioketal Cleavage Enabled by Enzymatic Bromide Recycling by Vanadium-Dependent Haloperoxidases

Thioketals are an important class of compounds that enable the selective preparation and protection of carbonyl compounds in chemical synthesis. Despite their synthetic utility, selective cleavage of thioketals often requires the use of harsh conditions and stoichiometric reagents that are largely bioincompatible. Herein, we describe a biocatalytic strategy for the selective cleavage of thioketals using enzymatic bromide recycling by vanadium-dependent haloperoxidase (VHPO) enzymes. This process involves thioketal cleavage through repetitive VHPO-mediated formation of hypohalous acid with a catalytic quantity of halide salt and hydrogen peroxide as the terminal oxidant. This method is demonstrated on a broad range of 1,3-thioketals in high yield and excellent chemoselectivity. The protocol has been demonstrated on gram-scale, run with lysate and whole cells, and has been extended to cleavage of 1,3-acetals, 1,4-thioketals, and 1,3-oxathiolanes.