A unique method has been developed for performing ?-C-alkylation of �-ketoesters using equilibrating bases.  Similar reaction conditions have been used for Knoevenagel condensation reactions (a-C-alkylation), while two equivalents of a much stronger base were thought to be necessary to perform ?-C-alkylation. Because similar reactants yield different products (?-C-alkylation vs. a-C-alkylation) for our reaction as compared with previously published methods, computational studies were undertaken to explore potential mechanisms for each reaction. The geometries and relative energies of reactants, intermediates, products, and transition states were calculated using density functional theory, both in vacuo and with a continuum solvent model. The results suggest the 3-oxo-5-phenyl-d-lactone forms via more stable intermediates than the Knoevenagel condensation product which, along with the greater stability of 3-oxo-5-phenyl-d-lactone anion product, may explain why 3-oxo-5-phenyl-d-lactone is favored over the Knoevenagel condensation product.

Mechanistic investigation of γ-C-alkylation of β-ketoesters under equilibrating conditions using computational methods

245th National Meeting (2013)

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