Direct oxidative coupling of alcohols and amines is an environmental-benign and atomic-economy approach for imine synthesis. We disclosed that UiO-66 framework successfully confined Ru to single-atom scale with assistance of oxophilic Zn2+ promoter. This [email protected] catalyst showed a highest TOF of 78 h-1 among all Ru catalysts in literature and attained > 99% yield to benzylideneaniline in the model reaction in an O2 atmosphere at a low temperature without alkaline additives. In addition, this catalyst demonstrated satisfying gram-scale imine synthesis, wide substrate scope and stable reusability. Kinetic investigations and in situ characterizations allowed getting insights to active sites, amphoteric carrier and reaction mechanism. Dynamic interactions between Ru and Zn based on their ratios induced electron-deficient Ru0 active sites promoted by oxophilic Zn2+ species. Hence, primary alcohols can be efficiently converted to the corresponding aldehydes using molecular O2, i.e., the rate-determining step. Besides, Zr4+-O2- pairs on UiO-66 provided adequate acidic-basic sites for the tandem catalysis.