Knoevenagel reactions with β-oxo acids. Regiospecific enol equivalents for syntheses of α,β-unsaturated ketones and of some β-ketols

Abstract

3-Oxobutanoic acid reacts with aliphatic aldehydes in the presence of pyridine to give α,β-unsaturated methyl ketones in good yields. Analogous results were obtained with a series of other β-oxo acids. Synthesis of (E)-7-methyloct-4-en-3-one, a major constituent of the marine sponge Plakortis zygompha, has been carried out using this methodology. Aromatic aldehydes are generally less reactive under these conditions but give β-ketols when the phenyl ring bears an electron-withdrawing substituent. Some observations on the mechanism of the reaction between 3-oxobutanoic acid and benzaldehyde are presented.