Pdδ+ Formation Induced by Electronic Metal-Support Interaction Enables Efficient Continuous-Flow Hydrogenation of Pyridine to Piperidine.

The growing demand for pharmaceutical intermediates has intensified the need for efficient and sustainable routes to piperidines, key heterocyclic scaffolds widely used in drug synthesis and fine chemical production. Herein, we reported a highly active Pd/θ-Al₂O₃ catalyst via a liquid-phase reduction method, affording uniformly dispersed Pd nanoparticles on θ-Al₂O₃ nanosheets for the continuous-flow hydrogenation of pyridines to piperidines under mild conditions. Experiment results reveal strong electronic metal-support interactions (EMSI) between Pd and θ-Al₂O₃, which induces interfacial electron transfer and generates Pdδ+ species. These electronically modulated active sites optimize pyridine adsorption and facilitate piperidine desorption, thereby enhancing catalytic efficiency and resistance to nitrogen-induced poisoning. Under optimized flow conditions (150 °C, 3 MPa, H₂/oil = 300), the Pd/θ-Al₂O₃ catalyst achieves nearly complete pyridine conversion with >99% selectivity for piperidine and maintain good stability over 25 cycles. Density functional theory (DFT) calculations reveal that EMSI can enhances adsorption of the substrate, improving hydrogenation kinetics. The catalyst also exhibits broad substrate scope and high tolerance toward diverse functional groups, which provides mechanistic insight into the role of EMSI in regulating catalytic performance and offers a practical strategy for scalable, safe, and selective continuous-flow hydrogenation of nitrogen-containing aromatic compounds.