A CATALYTIC ASYMMETRIC-SYNTHESIS OF N-BOC-BETA-METHYLPHENYLALANINES

An efficient, stereodivergent, and enantioselective synthesis of the s yn and anti diastereomers of N-Boc-beta-methylphenylalanine has been d eveloped. Starting from enantiomerically pure (2S,3S)-2,3-epoxy-3-phen yl-1-propanol, a three-step sequence, consisting of the oxidation of t he primary alcohol up to the carboxyl stage, ring opening of the epoxy acid with Me2CuCNLi2, and esterification of the resulting hydroxy aci d with methyl iodide, leads to the hydroxy ester anti-10, which has be en converted in a stereodivergent manner into both the (2S,3R) and the (2R,3R) diastereomers of N-Boc-beta-methylphenylalanine, syn-1 and an ti-1, respectively. Activation of the secondary hydroxy group in anti- 10 as a mesylate, followed by nucleophilic displacement with sodium az ide, hydrogenolysis with simultaneous protection of the amino group, a nd saponification with LiOH, affords syn-1. The same reaction sequence applied to syn-10, obtained in turn by Mitsunobu reaction of anti-10 with p-nitrobenzoic acid followed by the hydrolysis of the resulting p -nitrobenzoate, leads tb anti-1. Both products have been obtained with greater than or equal to 99% enantiomeric excess.