Acylation of alcohols and amines is one of the most fundamental reactions. Due to the greater nucleophilicity of the amino group compared to the hydroxyl group, complete N-acylation occurs. Only an enzymatic reaction can promote a highly selective O-acylation reaction, and there are no examples using an artificial catalyst. Here we report that the tetranuclear zinc cluster Zn(4)(OCOCF(3))(6)O efficiently catalyzes highly chemoselective O-acylation in the presence of primary and secondary alkyl amines. Our results suggest the high potential of the zinc cluster as the core structure of an artificial enzyme to realize further enzyme-like chemoselective reactions.