The catalytic potential of atomically precise quantum-sized gold nanoclusters (Au38(SC2H4Ph)24) is explored for the three-component coupling of an aldehyde, an alkyne and an amine to synthesize propargylamines. A high catalytic efficiency with a very low loading (0.01 mol%) is achieved. Furthermore, the synergistic effect of the electron-deficient surface (i.e. Auδ+, 0 < δ+ < 1) and the electron-rich Au23 core of the ligand-protected nanoclusters is critical for this catalytic reaction.