A Green and Highly Selective Approach to Copper-Catalyzed Transfer Hydrodeuteration of Alkenes and Alkynes Using D2O.

Precisely labeled small molecules are critical for advancing research in many areas of science, especially in the discovery of deuterated drugs. While reductive deuteration is highly effective for the selective labeling of organic compounds, reactions generally require the use of harsh, toxic, and environmentally harmful chemicals. Herein, we report a general Cu-catalyzed transfer hydrodeuteration of alkenes and alkynes to access deuterated products in a highly selective manner. The reaction utilizes green and environmentally benign reagents including the use of D2O as the deuterium source, poly(methylhydrosiloxane) (PMHS) as the hydride transfer reagent, and 2-methyltetrahydrofuran (2-MeTHF) as the solvent. The development of a slow addition protocol to circumvent catalyst sequestration by D2O was identified as the key to success for this green strategy. The applicability of the reaction for the late-stage synthesis of deuterated drug molecules and natural product analogs is highlighted in this work. Furthermore, a highly enantioselective synthesis of enantioisotopomers was also achieved using this sustainable protocol.