Atomically precise ultrasmall copper cluster for room-temperature highly regioselective dehydrogenative coupling

Abstract Three-component dehydrogenative coupling reactions represent important and practical methodologies for forging new C–N bonds and C–C bonds. Achieving highly all-in-one dehydrogenative coupling functionalization by a single catalytic system remains a great challenge. Herein, we develop a rigid-flexible-coupled copper cluster [Cu 3 (NHC) 3 (PF 6 ) 3 ] (Cu 3 NC (NHC) ) using a tridentate N-heterocyclic carbene ligand. The shell ligand endows Cu 3 NC (NHC) with dual attributes, including rigidity and flexibility, to improve activity and stability. The Cu 3 NC (NHC) is applied to catalyze both highly all-in-one dehydrogenative coupling transformations. Mechanistic studies and density functional theory illustrate that the improved regioselectivity is derived from the low energy of ion pair with copper acetylide and endo -iminium ions and the low transition state, which originates from the unique physicochemical properties of the Cu 3 NC (NHC) catalyst. This work highlights the importance of N-heterocyclic carbene in the modification of copper clusters, providing a new design rule to protect cluster catalytic centers and enhance catalysis.