Thiourea Dioxide (TDO)-Mediated Switchable Mono- and Dihydro(deutero)dechlorination of Trichloroacetamides

Abstract

CCl2H and CClH2 skeletons (and their deuterated analogues) have attracted substantial interest in modern drug discovery, rendering the hydro(deutero)dechlorination of readily accessible trichloromethyl precursors a powerful strategy for the modular construction of these privileged motifs. However, achieving the precise replacement of chlorine atoms with high chemoselectivity remains a significant synthetic challenge. Herein, we report a transition-metal-free, operationally simple protocol for the controlled mono- and dihydro(deutero)dechlorination of trichloroacetamides using thiourea dioxide (TDO). By facile modulation of temperature and reaction time, the method enables selective removal of one or two chlorine atoms, affording mono- or dihydro(deutero)dechlorinated products, respectively. The process is compatible with a wide range of functional groups and utilizes H2O and D2O as safe and inexpensive souces of hydrogen and deuterium, respectively.