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

α,β-Unsaturated ketones can be prepared by reaction of differently substituted β-keto acids and aldehydes. The reaction is carried out under organocatalysis (β-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 α,β-unsaturated ketones can be prepared. An example of a hydroformylation/Verley-Doebner Knoevenagel telescoped process is also described. The conditions used in the Knoevenagel reaction to prepare conjugated esters under amino acid organocatalysis can be applied also for the synthesis of α,β unsaturatedketones. β-Keto acids are prepared byhydrogenolysis of the corresponding benzyl ester and react easily with aldehydes to give the α,β-unsaturated ketones without formation of high molecular weight byproducts. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.