Theoretical approach towards the understanding of asymmetric additions of dialkylzinc to enals and iminals catalysed by [2.2]paracyclophane-based N,O-ligands

The 1,2- and 1,4-asymmetric additions of dialkylzinc reagents (ZnMe(2) and ZnEt(2)) to cinnamaldehyde and N-formylbenzylimine catalysed by 2.2]paracyclophane-based N,O-ligands were studied with quantum chemical methods. High level LPNO-CEPA/1 (local pair natural orbital coupled electron pair approximation 1) calculations were performed to obtain reliable reaction barriers and binding energies. The calculations supported the experimentally observed selectivities. In the reaction, the alkyl transfer takes place on a binuclear zinc complex. Regioselectivity can be traced back to changes in π-conjugation. Because the less conjugated N-formylbenzylimine is more flexible, it is better suited for 1,4-additions. Moreover, bulky ligands were shown to be important for stereoselectivity. The reason is that the tricyclic motif present in the transition states is sterically less hindered in the anti conformation. Based on the LPNO-CEPA/1 data, a set of popular theoretical methods are validated. Although it was possible to set up a procedure to obtain the stereoselectivities with computationally less demanding methods, this was not possible for the regioselectivity of the reactions.