Heterometallic oxo clusters have been attracting intensive interest due to their unique properties originating from the synergistic interactions between different components. Herein, we report the construction and catalytic applications of a family of copper-doped polyoxo-titanium clusters (Cu-PTCs) coordinated with different acetate derivative ligands. The solvothermal reactions of metal salts and trimethylacetic acid or 1,2-phenylenediacetic acid in ethanol produced Ti6Cu3(μ3-O)4(μ2-O)(OEt)16(L1)4 (L1 = trimethyl acetate, PTC-367) and H2Ti8Cu2Br2(μ4-O)2(μ2-O)4(OEt)20(L2)2 (L2 = 1,2-phenylenediacetate, PTC-368), respectively. When smaller acetic acid was introduced as a stabilizing ligand, higher nuclei H2Ti16Cu3(μ4-O)5(μ3-O)15(μ2-O)3(OiPr)18(Ac)8 (Ac = acetate, PTC-369) and H3Ti29Cu3(μ4-O)6(μ3-O)30(μ2-O)8(OiPr)17(Ac)20 (PTC-370) were prepared. The number of metal ions exposed on the surface of the four clusters changes due to variations in the steric hindrance of functionalizing ligands, and theoretically, so does their catalytic activity as Lewis acids. In light of this, we conducted a carbon dioxide cycloaddition reaction in an atmospheric environment and the four obtained compounds displayed increasing catalytic activities from PTC-367 to PTC-370. These results provide a feasible synthetic method for modulating the structures of Cu-doped titanium oxide materials and improving their catalytic activities.