Process-scale preparation of enantiomerically pure γ-lactones by asymmetric hydrogenation of γ-ketoesters and comparative tests of the sensory properties of some antipodes

A reliable methodology, applicable on a process-scale level, for producing enantiomerically pure chiral gamma-lactones by enantioselective hydrogenation of gamma-ketoesters, followed by cyclisation of the resulting gamma-hydroxyesters, has been developed. The multi-step procedure was transformed into a one-pot reaction. A very efficient chiral Ru-complex, based on the bilieteroaromatic diphosphine ligand tetraMe-BITIOP, was developed as a catalyst, capable of coupling fast kinetics with high stereoselection levels. Its structure was fully elucidated through P-31 NMR, EPR and X-ray single-crystal analyses. The optimal experimental conditions are as follows: hydrogen pressure = 30 psi, S/C ratio = 2000, 30% in weight substrate concentration. Yields are quantitative and enantiomeric excesses in the range 98-99.9%. Sensorial tests on the antipodes of two gamma-lactones demonstrated the very different properties of the enantiomers. (C) 2004 Published by Elsevier Ltd.