Enantioselective addition of diethylzinc to benzaldehyde catalysed by chiral, bridged resorcinarenes: a stereoselectivity model based on chirality transfer

The enantioselective addition of diethylzinc to benzaldehyde catalysed by a range of chiral bridged resorcinarenes has been studied, and the results used as a means of probing cooperative effects in the resorcinarene bowl. A structure-activity relationship has emerged in which bridged resorcinarenes with little available room in the bowl (e.g., 3b, 3c) favour R-enantioselectivity in the product, while those promoting cooperative effects in the bowl via coordination sites in the bridge (3e) or strong donor protecting groups (3j) favour S-enantioselectivity. A mechanistic hypothesis based on Noyori's model to account for these trends has been put forward in which stereoselectivity is dependent on two factors as the ratio of axially diastereomeric anti-zincoxazines as well as the exo or endo bias of active zinc. The model explains why ee's are never greater than around 50% and indicates asymmetric induction to be due to the axial chirality in the bowl as a result of chirality transfer from the bridge, rather than due to induction via the central chirality in the line of the bridge. As a result, the model stimulates some new fascinating possibilities in enzyme mimicry.