Constructing Pd and Cu Crowding Single Atoms by Protein Confinement to Promote Sonogashira Reaction

For multicenter‐catalyzed reactions, it is important to accurately construct heterogeneous catalysts containing multiple active centers with high activity and low cost, which is more challenging compared to homogeneous catalysts because of the low activity and spatial confinement of active centers in the loaded state. Herein, a convenient protein confinement strategy is reported to locate Pd and Cu single atoms in crowding state on carbon coated alumina for promoting Sonogashira reaction, the most powerful method for constructing the acetylenic moiety in molecules. The single‐atomic Pd and Cu centers take advantage in not only the maximized atomic utilization for low cost, but also the much‐enhanced performance by facilitating the activation of aryl halides and alkynes. Their locally crowded dispersion brings them closer to each other, which facilitates the transmetallation process of acetylide intermediates between them. Thus, the Sonogashira reaction is drove smoothly by the obtained catalyst with a turnover frequency value of 313 h−1, much more efficiently than that by commercial Pd/C and CuI catalyst, conventional Pd and Cu nanocatalysts, and mixed Pd and Cu single‐atom catalyst. The obtained catalyst also exhibits the outstanding durability in the recycling test. This work reports a convenient protein confinement strategy that tightly locates crowded Pd and Cu single atoms to promote the substrate activation and transmetallation in the Sonogashira reaction. These results provide important clues for the efficient construction of high‐performance heterogeneous catalysts with multiple neighboring active centers and achieving valuable organic transformations cocatalyzed by multiple active centers.