Absence of Non-Linear Effects Despite Evidence for Catalyst Aggregation

An in-depth study of the catalytic system, consisting of the enantioselective addition of ZnEt to benzaldehyde with (1R,2S)-(−)-N-Methylephedrine (NME) as chiral ligand, suggests the presence of dimeric and trimeric aggregates, as deduced from product ee vs. catalyst loading and NMR investigations (H, DOSY). Formation of catalyst aggregation was excluded in earlier studies as this system displays a linear product ee vs. ligand ee-correlation, which is usually taken as an indication for the absence of catalyst aggregation. A subsequent theoretical study, using the monomer-dimer competition model, which we have recently developed, highlights the possible parameter configurations leading to linear product ee vs. ligand ee plots – despite the presence of catalyst dimers. It shows that, while the Kagan and Noyori models allow linearity in very specific cases only, a multitude of scenarios may lead to linearity here, especially if heterochiral dimers are catalytically active.