Our recent work has been focusing on the heterogeneous synthesis of flavanone over magnesia catalysts, as an alternative to the homogeneously catalyzed process. Continuing our systematic investigation this study focuses on the nature of the active sites involved in this reaction. The adopted research strategy includes the controlled modification of a conventional MgO catalyst by both decreasing and increasing its basicity. To decrease the basicity of MgO, different anions (PO43–, SO42–, F–, and Cl–) were used and partial results were reported earlier [1]. An increase in the basicity of magnesia was achieved by doping lithium. A series of catalysts with lithium loadings of 0, 0.05, 0.1, 0.5, 1.0, 5.0, and 10.0 wt. % were prepared using pure magnesia powder (Aldrich, 65 m2/g) and aqueous solutions of lithium nitrate, as the precursor. Samples were calcined in air at 750oC for 24 h before use. Catalysts were characterized by measurements of the specific surface area (SBET), powder X-ray diffraction, HR-TEM, CO2 TPD and in situ infrared spectroscopy (FTIR) of pre-adsorbed CO2, benzaldehyde and 2'-hydroxyacetophenone in an attempt to characterize the catalytic behavior. Catalytic tests were performed in a batch reactor system in a mixture containing 1.5 M benzaldehyde and 1.5 M 2'-hydroxyacetophenone in DMSO. Increasing basicity has generally a beneficial effect on the selectivity of flavanone as desired product. The results indicate a strong increase of the initial reaction rate for Li-loadings up to 0.1 wt. %. Higher lithium loadings result to a dramatic decrease of the specific surface area of the catalysts and consequently lower initial reaction rates reported per catalyst weight. Lithium doping of magnesia results to increase basicity as indicated by the results of TPD and FTIR studies. We propose that a conjugate Lewis acid-base pair (Mg2+–O2‾) is involved in the activation of 2'-hydroxyacetophenone, in which the surface O2‾ anion abstracts an H+ from the hydroxyl group of 2'-hydroxyacetophenone to produce an anionic intermediate. Exchange of the Mg2+ cation of the MgO lattice by Li+ results in a decoration of the surface by Li+O‾ groups which increase the local electronegativity. Consequently, the ability to abstract H+ from the hydroxyl group of 2'-hydroxyacetophenone is enhanced in the presence of Li. The decrease of activity at high Li loadings is due to particle agglomeration, as well as the formation of unreactive carbonates observed by XRD, which can block the active sites.