Mechanochemical Dehalogenative Deuteration of Alkyl Halides Through Piezoelectric Catalysis Initiated by a Single‐Electron Oxidation Strategy

Deuterium labeling is extensively utilized across various scientific disciplines. The dehalogenative deuteration of organic halides offers a promising approach for achieving deuterium labeling. However, existing methods for dehalogenative deuteration primarily focus on sp2-hybridized aryl halides, while sp3-hybridized alkyl halides, especially bromides and chlorides, exhibit low reactivity and pose significant challenges for reduction. This limitation hampers the development of deuteration methodologies. In this study, a robust and versatile mechanochemical strategy is introduced for deuterating both activated and unactivated alkyl halides (X = Cl, Br, I), employing D2O as an economical deuterium source and electron donor, catalyzed by a piezoelectric material. Importantly, unlike previously mechanochemical piezoelectric catalysis reactions that are typically initiated by a single-electron reduction process, this transformation is triggered by a single-electron oxidation pathway. Employing this innovative technique, a variety of organic halides are successfully converted, including primary, secondary, and tertiary alkyl halides, into deuterated products with good yields and high deuterium incorporation, using only a chemically equivalent amount of D2O. The practical application of this green and efficient methodology is further demonstrated by late-stage deuteration on drug molecule analogs, underscoring its potential utility in pharmaceutical development.