Qi Haifeng, Jiao Yueyue, Duan Jianglin, Dummer Nicholas F, Zhang Bin, Ren Yujing, Taylor Stuart H, Qin Yong, Junge Kathrin, Jiao Haijun, Hutchings Graham J, Beller Matthias
Leibniz-Institut für Katalyse e. V., Rostock, Germany.
Max Planck-Cardiff Centre on the Fundamentals of Heterogeneous Catalysis FUNCAT, Translational Research Hub, Cardiff University, Cardiff, UK.
Nat Commun. 2025 Feb 21;16(1):1840. doi: 10.1038/s41467-024-55722-9.
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.
氘代胺是药物合成和新药物代谢物鉴定的关键构建单元,这推动了人们寻找通用、高效且广泛适用的此类化合物选择性合成方法。在此,我们描述了一种具有高度分散的孤立金属位点的多功能磷掺杂碳负载铁催化剂,该催化剂可实现串联还原胺化 - 氘代反应序列。优化后的磷改性铁基催化剂在多种氘代苯胺、胺、生物活性配合物和药物(>50个实例)的反应性和区域选择性方面均表现出优异性能。克级规模实验和催化剂循环实验展示了该方法的应用潜力。除了所开发方法的直接适用性外,所描述的方法为其他增值有机合成中多功能单原子催化剂的开发开辟了前景。