The Synthesis of the High-Potency Sweetener, NC-00637. Part 1: The Synthesis of (S)-2-Methylhexanoic Acid

The synthesis of the high potency sweetener candidate NC-00637 (1) required large quantities of (S)-2-methylhexanoic acid (2). This acid was first prepared in small quantities by the use of chiral auxiliaries. For large quantities, resolution by classical means and an enzymatic method were investigated. Asymmetric hydrogenation provided a workable solution.