Chiral Metal–Malate Coordination Scaffolds as Smart Supramolecular Platforms for Asymmetric Induction in Aqueous Radical Chemistry

This work presents a conceptual reframing of chiral iron(II) and copper(II) (L)-malate complexes as smart supramolecular scaffolds: dynamic coordination platforms that translate molecular recognition into functional asymmetric induction. In the Fenton-type oxidation of glycerol, these scaffolds create a chiral coordination microenvironment that directs hydroxyl radical attack toward enantioselective C–H abstraction. The chirality of sugars, defined by the specific three-dimensional arrangement of substituents around their asymmetric carbon centres, dictates their recognition and utilisation by enzymes, transporters, and other biomolecular machinery, and biological systems have evolved a marked preference for D-enantiomers as a consequence of the homochiral nature of the enzymes that metabolise them. Here, we exploit prochiral glycerol, an achiral molecule whose central C-2 carbon bears two enantiotopic terminal hydroxymethyl (–CH2OH) arms, as a substrate for asymmetric induction. Experimental data show that the Fe(II)-(L)-malate scaffold affords a reproducibly larger optical rotation than the Cu(II)-(L)-malate scaffold, both consistent in sign with preferential formation of (R)-glyceraldehyde. Using glyceraldehyde concentrations independently determined by quantitative Benedict’s titration on the same reaction mixtures (n = 3 per catalyst), concentration-corrected ee values of 59.1% (Fe) and 29.9% (Cu) were obtained, corresponding to 13.6% and 13.5% glycerol conversion over the reaction. The qualitative iron-over-copper ordering, and the approximate magnitude of the differential, are therefore supported by concentration-normalised measurements. Product identity was further confirmed by ESI-MS on the actual reaction samples, and, most importantly, the reported ee values were independently supported by preparative chiral column (Chiralpak IA, Daicel Corporation, Osaka, Japan) performed directly on the same 30 min reaction aliquots against authentic glyceraldehyde standards, giving ee values of 60.0% ± 2.5% (Fe) and 29.2% ± 2.3% (Cu) (mean ± SD, n = 3 per catalyst), in agreement with polarimetry within experimental uncertainty, from the physically isolated enantiomers. Because these cromatography-derived values are calculated from the masses of the isolated fractions rather than from validated analytical peak-area integration, this analysis is presented as an independent chirality-resolving confirmation, not as a fully validated quantitative method. This differential may be rationalised, as a mechanistic interpretation rather than an experimentally established causal relationship, by a proposed more rigid inner-sphere coordination cage of iron relative to a more labile copper environment. Acid activation (pH ≈ 2.0) acts as a “smart” trigger: in the absence of sulfuric acid, no optical activity is observed. The observed optical rotation changes by less than 10% when the catalyst loading is halved or doubled; after correction for the accompanying change in conversion, the ee is maintained at half loading but decreases at double loading (by about 20% for Fe and 10% for Cu), suggesting partial racemisation of the product and/or a less selective oxidation pathway at higher metal concentration. These results establish a proof of concept for stimuli-responsive supramolecular scaffolds that combine molecular recognition, catalytic function, and sustainability, opening a route to optically active building blocks from renewable glycerol.