Enantiospecific alkylations of alanine

Abstract

Reaction of ferrocenecarbaldehyde 3 with sodium (S)-alaninate followed by pivaloyl chloride generates (2S,4S)-2-ferrocenyl-3-pivaloyl-4-methyl-1,3-oxazolidin-5-one 5 (>98% de). Compound 5 undergoes stereospecific 4-alkylation with complete retention of configuration on treatment sequentially with lithium diisopropylamide and an appropriate alkyl bromide {benzyl bromide, allyl bromide, crotyl [(E)-but-2-enyl] bromide, α-bromo-o-xylene, cinnamyl bromide, 2-(bromomethyl)naphthalene, 1-(tert-butoxycarbonyl)-3-(bromomethyl)indole and bromoacetonitrile} to generate the corresponding (2S,4R)-2-ferrocenyl-3-pivaloyl-4-alkyl-4-methyl-1,3-oxazolidin-5-ones 7a–h. Hydrolysis of (2S,4R)-7a–h on Amberlyst-15 generates the free (R)-α-methyl-α-amino acids (R)-8a–h.