Influence of alkylating reagent softness on the regioselectivity in enolate ion alkylation: A theoretical local hard and soft acids and bases study

C-Alkylation and O-alkylation of ethyl acetoacetate by a series of alkylati ng agents is investigated, in the gas phase as well as in the solvent, with in a local viewpoint of the hard and soft acids and bases (HSAB) principle at the Hartree-Fock level using a 3-21+G* basis set. The Gazquez and Mendez formula for calculating the interaction energy is used to reveal the influ ence of the alkylating agent softness on the two possible orientations in t he ethyl acetoacetate alkylation. O-Alkylation was found to be favored by a hard alkylating agent, whereas C-alkylation becomes less and less disfavor ed upon increasing softness.