Hexafluorophosphate‐Triggered Hydrogen Isotope Exchange (HIE) in Fluorinated Environments: A Platform for the Deuteration of Aromatic Compounds via Strong Bond Activation
Year: 2024
Type: article
Abstract: 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 6 − ) in deuterated 1,1,1,3,3,3‐hexafluoroisopropanol (HFIP‐ d 1 ) and D 2 O. 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 1 activates the typically inert P−F bond in PF 6 − for D 2 O addition. The thus in situ formed DPO 2 F 2 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.
Authors: Yang Ni, Jonathan Lebelt, Milena Barp, Florian Kreuter, Hannah Buttkus, Jiaye Jin, Martin Kretzschmar, Ralf Tonner‐Zech, Knut R. Asmis, Tanja Gulder
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,510
OpenAlex ID: W4404558611