Regiospecific deoxygenative deuteration of ketones via HOME chemistry

Abstract

Historically, deuteration reactions have been primarily utilized for mechanistic studies, but recently, their pharmacological importance has been recognized. Many efforts have been made to fulfill the urgent need for deuteration tools since the FDA's approval of the first deuterated drug used to treat chorea-associated Huntington's disease. Current deuteration strategies prevailingly involve reversible H/D exchange at the target C–H bond and suffer from low functional group tolerance and deuterium content. Herein, a ruthenium-catalyzed deoxygenative deuteration of ketones is developed with 20 examples under mild conditions. The reaction proceeds via HOME chemistry (hydrazone as organometallic equivalent) followed by in situ deuteration, thereby enabling regiospecific deuteration at the methylene site with 91% to 96% deuterium content.