Hexafluorophosphate‐Triggered Hydrogen Isotope Exchange (HIE) in Fluorinated Environments: A Platform for the Deuteration of Aromatic Compounds via Strong Bond Activation

There is a perpetual need for efficient and mild methods to integrate deuterium atoms into carbon frameworks through late‐stage modifications. We have developed a simple and highly effective synthetic route for hydrogen isotope exchange (HIE) in aromatic compounds under ambient conditions. This method utilizes catalytic amounts of hexafluorophosphate (PF6−) in deuterated 1,1,1,3,3,3‐hexafluoroisopropanol (HFIP‐d1) and D2O. Phenols, anilines, anisoles, and heterocyclic compounds were converted with high yields and excellent deuterium incorporations, which allows for the synthesis of a wide range of deuterated aromatic compounds. Spectroscopic and theoretical studies show that an interactive H‐bonding network triggered by HFIP‐d1 activates the typically inert P‐F bond in PF6‐ for D2O addition. The thus in‐situ formed DPO2F2 triggers then HIE, offering a new way to deuterated building blocks, drugs, and natural‐product derivatives with high deuterium incorporation via the activation of strong bonds.