Pyridine-mediated tandem Knoevenagel condensation-decarboxylation: Chemoselectivity, mechanistic rationale, and discovery of a novel Lead(II) fumarate coordination polymer.

The pyridine-mediated tandem Knoevenagel condensation-decarboxylation of glyoxylic acid and malonic acid was investigated at 95 °C in neat anhydrous pyridine to establish the mechanistic basis of its strict substrate specificity and to characterise the coordination compound formed during lead(II) acetate-mediated product isolation. Fumaric acid was isolated in 92% yield with confirmed trans-stereoselectivity. Control reactions with glycolic acid, succinic acid, and DL-malic acid as structural analogues of the methylene component uniformly failed to afford fumaric acid, establishing the mechanistic indispensability of three concurrent properties unique to malonic acid: high methylene C-H acidity (pKa = 2.83), resonance-stabilised enolate nucleophilicity, and the β-keto acid intermediate geometry enabling facile six-membered cyclic decarboxylation. Density functional theory calculations at the r2SCAN-3c/SMD (pyridine) level show that direct decarboxylation via transition state TS4b is preferred over the competing dehydration-decarboxylation sequence via TS4a by ΔΔGsolv‡= 9.5 kcal mol-1. Treatment of the product with lead(II) acetate yielded an unexpected white precipitate characterised by HR-ESI-MS, titrimetric lead determination, elemental analysis, and PXRD as the coordination polymer [PbO(C4H2O4)]·3H2O, rather than the dihydrate salt [Pb(C4H2O4)]·2H2O reported previously. HR-ESI-MS isotopic pattern analysis confirms a polymeric rather than discrete molecular architecture. This result resolves a century-old structural discrepancy between the Rieckher (1844) and Weiss-Downs (1923) reports, attributing the divergent product architectures to counter-anion-controlled local pH during precipitation. Optimised Cartesian coordinates, total energies, zero-point vibrational energy corrections, and imaginary frequencies for all DFT-located stationary points are provided in the Supplementary Information.