The alkylation of 4-methoxymethyl-γ-butyrolactone enolate with methyl chloride was studied at the B3LYP/6-31+G* level. Conformer search of the free enolate gave 15 unique conformers within 5.39 kcal/mol. The transition structures for both anti- and syn-attacks of methyl chloride on these 15 conformers were located. In all cases, the anti-transition structures are more stable than the corresponding syn-ones. The alkylation of γ-valerolactone was studied at the MP2, B3LYP, and HF levels of theory with the 6-31 +G* basis set in the presence of Li+ and dimethyl ether molecules. Basis set effects were also examined by the comparison of the MP2 results with the 6-31 +G*, 6-31 +G**, and 6-311 +G** basis sets in one case. This study shows that the main source of the anti-selectivity of 4-substituted γ-butyrolactones is eclipsing strain in the syn-transition structures.