Palladium-catalysed enantioselective synthesis of ibuprofen

A general strategy has been developed for the enantioselective synthesis of alpha-aryl propanoic acids. Palladium-catalysed asymmetric allylic substitution is used as the key step of the synthesis. Compound 2a was obtained in 95% ee from the allylic substitution reaction of 1,3-diphenylprop-2-enyl acetate la with bis(phenylsulfonyl)methane, catalysed by palladium and oxazoline ligand 9. Ozonolysis, desulfonylation followed by oxidation furnished (S)-2-phenylpropanoic acid 4a without detectable loss of enantiomeric purity. The same synthetic strategy was employed to obtain Ibuprofen 4b in 87% ee, starting from acetate 1b. (C) 2002 Elsevier Science B.V. All rights reserved.