Synthesis of pyrazolidinone analogs of β-lactam antibiotics

5-Substituted pyrazolidin-3-ones, easily available by the conjugate addition–rearrangement of hydrazine to the 2,3-unsaturated sugar 1,5-lactones, react with 2 Ms equiv. of dimethyl acetylenedicarboxylate (DMAD) to give corresponding 2,3-dihydro-5,6,7-trimethoxycarbonyl-5-methoxycarbonylmethyl-1-oxo-1H,5H-pyrazolo[1,2-a]pyrazoles. Reaction proceeds via addition of the amine group of pyrazolidin-3-one to DMAD, rearrangement of the adduct leading to the azomethine-imine ylide followed by the 1,3-dipolar cycloaddition of second DMAD molecule. The cycloaddition product may undergo intramolecular addition of hydroxy group from the polyol side chain to the double bond to give tricyclic compounds. Reaction of pyrazolidin-3-one with DMAD is accompanied by the formation of several by-products, identification of which made possible to propose reaction pathway.