Stereoselective synthesis of some gamma- and delta-fluoro-alpha-amino acids

(R)-(-)-2-Amino-4-fluorobutyric acid (4c) (32% ee) and six of its homologues 9 have been synthesized by diastereoselective alkylation (54 -72% yield) of (R)-(+)-camphor-based glycine ester imines 1 with 1-bromo-2-fluoro-alkanes 6, at low temperature, followed by deprotection. Similarly 1-bromo-3-fluoropropane was used for the preparation of (R)-(-)-5-fluoronorvaline (4d) (42% ee). With 1-bromo-2-fluoropropane (6a) and its homologues (prepared by bromofluorination of 1-alkenes) partial resolution occurs in the alkylation step, yielding mixtures of four diastereomers. Using (R)-1-bromo-2-fluoro-4-methylpentane two diastereomeric alkylation products are formed (58% de). The overall yield of the three-step procedure varied from 10% to 32%.