Stereoselective synthesis of gamma-fluorinated alpha-amino acids using 2-hydroxy-3-pinanone as an auxiliary

(+)-(S)-2-Amino-4-fluorobutanoic acid (5a) (> 96% cc), its alpha -methylate d derivative (+)-(S)-5b (85% ee), and (-)-(S)-2-amino-4-fluoro-4-pentenoic acid (10) (81% ee) were synthesized by diastereoselective alkylation in the presence of LDA at low temperatures. Alkylation of (+)-(R,R,R)-2-hydroxy-3 -pinanone leased imines of glycine tert-butyl eater 1a or alanine isopropyl ester 1b with 1-bromo-2-fluoroethane (2) or 3-bromo-2-fluoropropene (7), r espectively, followed by step-wise deprotection was used. The selectivity o f the alkylation increased by lithium/magnesium exchange or for 1b also by addition of DMPU. Differences in the reactivity of enolate alkylations of e nantiomerically pure or racemic Schiif base 1a with 2 or 7, respectively, c an be explained by the formation of structurally different aggregates of th e enolates in solution, caused by diastereomeric interactions between enant iomers in the transition state of alkylation.