Tandem reductive amination and deuteration over a phosphorus-modified iron center

Abstract

Deuterated amines are key building blocks for drug synthesis and the identification of metabolites of new pharmaceuticals, which drives the search for general, efficient, and widely applicable methods for the selective synthesis of such compounds. Here, we describe a multifunctional phosphorus-doped carbon-supported Fe catalyst with highly dispersed isolated metal sites that allow for tandem reductive amination-deuteration sequences. The optimal phosphorus-modified Fe-based catalyst shows excellent performance in terms of both reactivity and regioselectivity for a wide range of deuterated anilines, amines, bioactive complexes, and drugs (>50 examples). Experiments on the gram scale and on catalyst recycling show the application potential of this method. Beyond the direct applicability of the developed method, the described approach opens a perspective for the development of multifunctional single-atom catalysts in other value-adding organic syntheses.