Synthesis of racemic and enantiopure 3,4-methanonipecotic acid

Abstract

The synthesis of both racemic and enantiomerically pure (1R,6S)-3,4-methanonipecotic acid, a cyclopropane-containing β-amino acid, which is a valuable building block for drug discovery, is described. The synthetic scheme commences from natural (S)-malic acid and allows for the preparation of the title compound in 12 steps in 28% overall yield. A novel approach to the racemic 3,4-methanonipecotic acid, which relies on a Simmons–Smith cyclopropanation as the key step, was also developed. In this case, the product was obtained in 8 steps and 38% total yield.