Asymmetric Alkylations of a Sultam‐Derived Glycine Equivalent: Practical preparation of enantiomerically pure α‐amino acids

Alkylation of the chiral glycine derivative 2 with “activated” organohalides under ultrasound‐assisted phasetransfer catalysis or with activated and nonactivated organohalides in anhydrous medium provides (mostly crystalline) alkylation products 3. Acidic hydrolysis of the pure products 3 gives (aminoacyl)sultams 4 which by mild saponification furnish pure α‐amino acids 5 in good overall yields from 2, along with recovered auxiliary 1 (Scheme 1). Pure ω‐protected α,ω‐diamino acids and α‐amino‐ω‐(hydroxyamino)acids 12–16 are readily accessible from (ω‐haloacyl)sultams 3 via reaction with N‐nucleophiles followed by acidic and basic hydrolyses (Scheme 2). A reliable determination of the enantiomeric purity of α‐amino acids using HPLC analysis of their N‐(3,5‐dinitrobenzoyl)prolyl derivatives 17 is presented.