A Symmetric dihydroxylation in an approach to the enantioselective synthesis of 2-anylpropanoic and non-steroidal anti-inflammatory drugs

Abstract

Naproxen ((S)-2-(6-methoxy-2-naphthyl)propanoic acid) and flurbiprofen ((S)-2-(3-fluoro-4-phenylphenyl)propanoic acid) have been synthesised in high enantiomeric excess. The synthetic strategy employed was to introduce asymmetry into the molecules by Sharpless asymmetric dihydroxylation of the appropriate methyl styrenes. The resultant diols were then converted into optically active epoxides and the required stereogenic centre was assembled by catalytic hydrogenolysis of the introduced benzylic epoxide oxygen bond, followed by oxidation of the derived optically active primary alcohol.