Process-scale preparation of enantiomerically pure b-lactones by asymmetric hydrogenation of beta-keto esters and comparative tests of the sensory properties of some antipodes

A reliable methodology, applicable on a process-scale level, for producing enantiomerically pure chiral c-lactones by enantioselective hydrogenation of c-ketoesters, followed by cyclisation of the resulting c-hydroxyesters, has been developed. The multi-step procedure was transformed into a one-pot reaction. A very efficient chiral Ru-complex, based on the biheteroaromatic diphosphine ligand tetraMe-BITIOP, was developed as a catalyst, capable ofcoupling fast kinetics with high stereoselection levels. Its structure was fully elucidated through 31P 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 oftwo c-lactones demonstrated the very different properties ofthe enantiomers.