Stereoselective Synthesis of Some γ‐ and δ‐Fluoro‐α‐amino Acids

Abstract (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‐fluornorvaline (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%.