NMR Measurements and Semi-Empirical Calculations in a First Approach to Elucidate the Mechanism of Enantioselective Cyanohydrin Formation Catalysed by Cyclo-(S)-Phe-(S)-His

A model was proposed for the stereochemical course of the highly enantioselective hydrocyanation of aromatic aldehydes catalysed by cycle-(S)-Phe-(S)-His (1). The conformation populations of 1 were determined by substituting the NMR coupling constants of the relevant protons in the Karplus equations. In addition the relative stabilities of these conformations were calculated using the semi-empirical AM1 and PM3 methods. The nature of the interaction between HCN and the imidazole moiety of 1 was calculated using a model system. No experimental evidence could be obtained for the interaction of benzaldehyde with 1 using NMR or IR.