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Superacid-Mediated Late-Stage Aromatic Polydeuteration of Pharmaceuticals
Emeline Appert1,2, Agnès Martin-Mingot1, Omar Karam2
1Superacid Group - Organic Synthesis Team, IC2MP, Université de Poitiers, UMR-CNRS 7285, 4 rue Michel Brunet, TSA 51106, 86073, Poitiers Cedex 9, France.
Abstract:
The field of medicinal chemistry is currently witnessing a deuterium rush owing to the remarkable properties of this element as bioisoster of hydrogen atom. Aromatic hydrogen isotope exchange (HIE) is one of the most studied strategies nowadays as it promises to access deuterium-modified drugs directly from their non-labeled parents. While most of the recent studies focus on metal-catalyzed C-H activation strategy, the use of superacidic conditions has been largely overlooked. This study shows that the use of TfOD as reaction medium allows the late-stage polydeuteration of a broad library of pharmaceuticals bearing a wide array of functional groups, complementing existing procedures.
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