Fenton-like chemistry enables catalytic oxidative desulfurization of thioacetals and thioketals with hydrogen peroxide

Abstract

(di-)Thioacetals and (di-)thioketals serve commonly as protecting groups of carbonyls and alcohols in organic synthesis, and therefore require highly efficient and chemoselective methods for desulfurization into carbonyls or alcohols. Although many approaches have been developed for such deprotection reactions, they usually employ toxic and/or expensive reagents under harsh conditions with a relatively long reaction time. Reported is a green catalytic approach that exploits Fenton-like chemistry (FLC: CeBr₃–H₂O₂) for the oxidative desulfurization of thioacetals and thioketals, which has many competitive advantages including (1) high efficiency (15 min, up to 97% yield), (2) high chemoselectivity with broad substrate scope, (3) greenness (H₂O as the sole waste) with outstanding green chemistry metrics, and (4) low cost. Detailed mechanistic studies revealed that the reactive brominating species (RBS, HOBr) generated in situ using Fenton-like chemistry (i.e., HO˙) and bromide reacted with sulfide (thioacetals or thioketals) to form the bromosulfonium intermediate (RR'S-Br), which was attacked by a heteroatom such as sulfur, oxygen or nitrogen to initiate the hydrolysis to carbonyls or alcohols. The released bromide ion (Br⁻) could be oxidized again by Fenton-like chemistry to generate RBS for the next catalytic cycle. This highly efficient, chemoselective, and green approach for oxidative desulfurization is expected to find wide applications in organic synthesis.