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 (PF ) in deuterated 1,1,1,3,3,3-hexafluoroisopropanol (HFIP-d) and DO. 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-d activates the typically inert P-F bond in PF for DO addition. The thus in situ formed DPOF then triggers HIE, offering a new way to deuterated building blocks, drugs, and natural-product derivatives with high deuterium incorporation via the activation of strong bonds.