Versatile Synthesis of 4-Methylidenepyrazolidin-3-ones Using a Horner–Wadsworth–Emmons Approach

Abstract

A new, versatile method for the synthesis of, so far unknown, variously substituted 4-methylidenepyrazolidin-3-ones as potential cytotoxic agents is described. Target compounds were synthesized from the corresponding 4-diethoxyphosphorylpyrazolidin-3-ones which were used as Horner–Wadsworth–Emmons ­reagents for the olefination of formaldehyde. 4-Phosphorylpyrazolidin-3-ones were, in turn, obtained starting from the sodium salt of ethyl 2-diethoxyphosphoryl-3-hydroxy-2-propenoate, ethyl 2-acyl-2-diethoxyphosphorylacetates, or 3-methoxy-2-diethoxyphosphorylacrylate and monosubstituted or 1,2-disubstituted hydrazines.