Thioacids as precursors for the synthesis of α,α-dideuterio alcohols using mild SmI2–D2O

Abstract

We report the first highly chemoselective single-electron transfer (SET) reductive deuteration of thioacids using SmI₂ and D₂O. This method uniquely affords α,α-dideuterio alcohols via highly reactive acyl radical intermediates, distinguishing it from the SET reduction of carboxylic acids, esters, and amides. The inherent high reactivity of thioacids enables the reaction to proceed under mild conditions, ensuring compatibility with a broad range of sensitive functional groups. With all 27 tested substrates, excellent regioselectivity and 98% deuterium incorporations were obtained. Furthermore, we demonstrated the potential of this protocol to introduce deuterium in medicinal chemistry.