Deuterated amine derivatives have emerged as valuable compounds in medicinal chemistry and materials science due to their enhanced metabolic stability and unique physicochemical properties, emphasizing the need for cost-effective and efficient deuteration catalysts; yet this topic has rarely been explored. In this work, we present an atomically dispersed Fe-P pair-site catalyst with high catalytic efficiency and regioselectivity in the deuteration of arenes and heteroarenes using D2O as the deuterated source. Remarkably, these metal-nonmetal Fe-P catalytic pairs with low Fe loading (0.15 wt %) achieve superior catalytic efficiency with a turnover frequency of 131.3 h-1, demonstrating activity up to 30 times higher than the state-of-the-art Fe nanoparticle catalyst (4.9 wt %, TOF: 4.5 h-1). Mechanistic investigations and density functional theory reveal that Fe-P pair sites play a key role in activating D2O and the substrate, enabling the regioselective deuteration of (hetero)-arenes. The investigation further demonstrates the remarkable performance of the phosphorus-doped Fe single-atom catalyst (SAC) across a diverse array of substrates, including various functional group-substituted anilines, nitrogen-containing heterocycles, phenol derivatives, and even complex drug molecules, yielding a total of 39 deuterated compounds. The scale-up synthesis of the Fe-P-C catalyst and subsequent stability tests further underscore the catalyst's potential for practical applications. This methodology introduces a promising direction for developing low-cost, non-noble metal SACs, offering significant potential for advancing the sustainable synthesis of fine chemicals.
Keywords: D2O activation; catalytic pair; deuteration; iron; single-atom catalyst.
© 2025 The Authors. Published by American Chemical Society.