ASYMMETRIC ALKYLATIONS OF A SULTAM-DERIVED GLYCINE EQUIVALENT - PRACTICAL PREPARATION OF ENANTIOMERICALLY PURE ALPHA-AMINO-ACIDS

Alkylation of the chiral glycine derivative 2 with 'activated' organohalides under ultrasound-assisted phase-transfer 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 alpha-amino acids 5 in good overall yields from 2, along with recovered auxiliary 1 (Scheme 1). Pure omega-protected alpha,omega-diamino acids and alpha-amino-omega-(hydroxyamino) acids 12-16 are readily accessible from (omega-haloacyl)sultams 3 via reaction with N-nucleophiles followed by acidic and basic hydrolyses (Scheme 2). A reliable determination of the enantiomeric purity of alpha-amino acids using HPLC analysis of their N-(3,5-dinitrobenzoyl)prolyl derivatives 17 is presented.