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

Thioketals are an important class of molecules used for the preparation and protection of carbonyl compounds in chemical synthesis. Selective cleavage of thioketals requires the use of harsh conditions and reagents that limit the use of thioketals in chemoenzymatic synthesis. Herein, we describe a biocatalytic strategy for the cleavage of thioketals using enzymatic bromide recycling by vanadium-dependent haloperoxidase (VHPO) enzymes. This reaction design involves halogenation-mediated thioketal cleavage through repetitive enzyme-mediated formation of hypobromous acid with a catalytic quantity of bromide salt and hydrogen peroxide as the terminal oxidant. This protocol is demonstrated on a broad range of 1,3-dithiolanes in high yield and excellent chemoselectivity, performed on a gram scale, run with lysate and whole cells, and applied to the cleavage of 1,3-dithianes and 1,3-oxathiolanes.