Substituents in Aromatic Aldehydes Determine Conditions and Chemoselectivity of Their Condensation with Trialkyl Phosphonoacetates

Although the Knoevenagel condensation of aldehydes with various CH-acids has been known for more than 130 years, the efficiency of this reaction for phosphonoacetates remains poorly understood. We found that the preferred conditions for the formation of target 3-(hetero)aryl-2-(dialkoxyphosphoryl)acrylates depend on the electronic properties of the aldehyde used. Specifically, for the Knoevenagel condensation of trialkyl phosphonoacetates with electron-deficient (hetero)aromatic aldehydes, the best results are achieved using a combination of piperidine and acetic acid as a catalyst, whereas for aldehydes containing an electron-rich aromatic group, higher yields were obtained using the pyrrolidine/acetic acid catalytic system. Preferred amines for catalyzing the reactions of aldehydes with diverse electroneutral aromatic groups were also identified. Secondary amines themselves can also be used to carry out this reaction without loss of efficiency. In contrast, tertiary amines were ineffective both alone and in combination with carboxylic acids. Based on the obtained data, the mechanistic picture of the Knoevenagel condensation of trialkyl phosphonoacetates and its competition with the Horner-Wadsworth-Emmons condensation was refined.