Absence of Non-Linear Effects Despite Evidence for Catalyst Aggregation

An in-depth study of the catalytic system, consisting of the enantioselective addition of ZnEt₂ 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 (¹H, DOSY). Formation of catalyst aggregate 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 we recently have 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.