Abstract
2-Hydroxy-5-methyl-3-hexanone was synthesised enantioselectively by Sharpless asymmetric dihydroxylation (Sharpless AD) or Shi's asymmetric epoxidation (Shi's AE) of 5-methyl-3-trimethylsiloxy-2-hexene. This was obtained in an E/Z ratio of 7.5/1 by deprotonation of 5-methyl-3-hexanone with NaHMDS in n-hexane followed by reaction with chlorotrimethylsilane. Optically active 2-hydroxy-5-methyl-3-hexanone was obtained in a 76.9% yield with a 75.6% ee when AD-mix-β was used as oxidant. Its absolute configuration was tentatively assigned to be R according to the AD face selection rule. AD-mix-α gave the product in a 69.2% yield only with a 15.7% ee. The major product had the same configuration as that obtained by AD-mix-β. Optically active 2-hydroxy-5-methyl-3-hexanone was obtained in a 54% yield with a 74.6% ee by Shi's AE when a catalyst derived from D-fructose was used, while in a 50% yield with a 72.8% ee when a catalyst derived from L-fructose was used. The absolute configuration of the product obtained by a catalyst from D-fructose was deduced to be R whilst a catalyst from L-fructose gave the (S)-enantiomer by comparison of the retention time on a chiral column G-TA with the product obtained by AD-mix-β.