Bradley University, Mund-Lagowski Department of Chemistry and Biochemistry, Peoria, IL 61606
Alkylation of the monoanion of an acetoacetate ester with benzaldehyde typically yields a Knoevenagel product (alpha-C-alkylation), but in an alcohol solvent, it has been found that a delta-lactone (gamma-C-alkylation) is formed. This simple procedure utilizes environmentally friendly reactantsto produce5-aryl-3-oxo-delta-lactones, a class of compounds that exhibit antimicrobial, antioxidant, and pain relieving properties.Based upon carbon-13 labeling and reactivity studies, it appears that thedelta-lactone is formed viadeprotonation at the alpha carbon of the acetoacetate ester followed by an intramolecular deprotonation at the gamma of the acetoacetate ester. The resulting highly reactive gamma anion then adds to the carbonyl carbon of the aldehyde generating a hydroxyketo ester, which then undergoes intramolecular transesterification. In addition to the mechanistic work, reactivity studies were performed to determine how substituents on the alpha or gamma carbons of an acetoacetate ester influence the outcome of the reaction.
[Abstract (DOC)]