A Stereoselective and Practical Synthesis of (E)-α,β-Unsaturated Ketones from Aldehydes

alpha,beta-Unsaturated ketones can be prepared by reaction of differently substituted beta-keto acids and aldehydes. The reaction is carried out under organocatalysis (beta-alanine, 0.5 equiv.) and generates the enones with high E selectivity (>95 %). This version of the Verley-Doebner modification of the Knoevenagel reaction is a practical alternative to the classic Horner-Wadsworth-Emmons (HWE) reaction without the formation of high molecular weight byproducts. The process makes use of simple reagents and can be applied to large-scale synthesis under conditions compatible with atom-economy principles. Differently substituted aliphatic, aromatic, or heteroaromatic alpha,beta-unsaturated ketones can be prepared. An example of a hydroformylation/Verley-Doebner Knoevenagel telescoped process is also described.