Tandem reductive amination and deuteration over a phosphorus-modified iron center
Haifeng Qi, Yueyue Jiao, Jianglin Duan, Nicholas F. Dummer, Bin Zhang, Yujing Ren, Stuart H. Taylor, Yong Qin, Kathrin Junge, Haijun Jiao, Graham J. Hutchings, Matthias Beller
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. Deuterated amines play a crucial role as building blocks in drug synthesis and in identifying metabolites of novel pharmaceuticals. This study introduces a dual-functional phosphorus-doped iron single-atom catalyst that efficiently enables both reductive amination and deuteration in a one-pot process, utilizing H2 as the reducing agent and cost-effective D2O as the deuterium source.