A UO22+ complex bearing N,N,N’,N’-tetraisopropyldiglycolamide (TiPDGA) and two DMF molecules was designed and prepared to explore a catalytic activities of the Lewis-acidic U centre. The cationic complex, [UO2(TiPDGA)(DMF)2]2+, was successfully obtained as a ClO4− salt under optimized reaction condition with appropriate mixing ratio between UO22+ and TiPDGA to maintain 1:1 stoichiometry, non-coordinating ClO4− counteranion to reserve coordination sites for substrate activation, and presence of extra HClO4 to suppress undesired hydrolysis of UO22+ competing with the expected complex formation. This UO22+ complex was thoroughly characterized by IR, elemental analysis, X-ray crystallography, and 1H NMR to confirm the desired [3+1+1] equatorial coordination is actually formed in the solid state, and still maintained even after dissolution in CD2Cl2. [UO2(TiPDGA)(DMF)2]2+ was further subjected to nucleophilic acyl substitution reactions of acid anhydrides to assess its activity and capability as a Lewis-acid catalyst there. Although the observed reaction rates are not very rapid, some characteristic aspects to gain reaction- and substrate-selectivity have appeared thanks to the equatorial coordination sphere sterically regulated by the tridentate auxiliary TiPDGA ligand and labile monodentate DMF molecules to activate an acid anhydride after ligand substitution.