Controlling selectivity in the reductive amination of carbonyls, a pivotal green route to amines, remains a long-standing challenge within complex reaction networks. Here, we report a strategy to precisely steer product selectivity by engineering the orbital symmetry of coordinatively unsaturated metal sites (CUSs) on metal-organic layers (MOLs) that support ruthenium nanoparticles (Ru NPs). Across diverse substrates, Zn-based MOLs with Zn2(CO2)4 paddle-wheel secondary building units (SBUs) favor primary amines, whereas their Cu-based analogues with Cu2(CO2)4 SBUs solely produce Schiff bases. This divergence originates from a picoscale symmetry-broken Cu-O4 geometry in the Cu2(CO2)4 unit, which weakens the adsorption and activation of Schiff base intermediates, thereby kinetically retarding their further ammonolysis. Our work establishes a paradigm for controlling catalytic selectivity through picoscale orbital symmetry manipulation at support metal sites.

Angew. Chem. Int. Ed. 2026, e8403490     doi.org/10.1002/anie.8403490