Modulating the Aggregation States of a Pd₆L₄ Cage for Selectivity Flipping during the Stereo‐Divergent Semi‐Hydrogenation of Alkynes

Abstract An enzyme‐mimicking catalytic system has been established using a singular palladium‐based octahedral cage as the supramolecular reactor, deftly unlocking the off‐on‐off selectivity in the semi‐hydrogenation of alkynes. Water serves as a critical regulator, modulating the catalyst states, reaction rates, and endpoints. The choice of solvent system influences the activity of host–guest binding and the reaction types of homogeneous and heterogeneous catalysis, effectively modifying the reaction steps involved in the Z → E isomerization during the semi‐hydrogenation of alkynes. Kinetic and inhibition experiments indicate that the catalyst mimics the binding and activation characteristics of enzymes towards substrates, enabling selective transformations within the confined enzyme‐mimicking environment. The utility of this switchable cage‐confined catalysis has been demonstrated in the synthesis and modification of complex biologically active molecules with controllable E / Z selectivity. This work sheds light on the design and control of artificial supramolecular counterparts of enzymes, offering fundamental insights into the factors influencing the activity and catalytic selectivity of biological macromolecules.