Methods for the synthesis of racemic and optically active title compou
nds are presented. Key step of these four-step procedures is the alkyl
ation with 1-bromo-2-fluoroalkanes of glycine-ester-derived imines in
anhydrous medium using lithium diisopropylamide as a base at low tempe
rature or phase transfer catalyzed alkylation with 50% NaOH and trieth
ylbenzylammoniumchloride as the phase transfer catalyst, respectively.
Subsequent three-step deprotection gave the free acids in 13-33% over
all yield. Deracemization of gamma-fluoro-alpha-aminobutyric acid meth
yl and ethyl esters with alpha-chymotrypsin was shown to give the (-)-
enantiomers of the esters and (+)-gamma-fluoro-alpha-aminobutyric acid
in >98% ee, while from the tert-butylester the opposite stereochemica
l result was observed giving the (-)-acid with 88% ee. Optically activ
e gamma-fluoro-alpha-amino acids were synthesized alternatively by pha
se transfer catalysis with N-benzyl-cinchonium chloride or using an au
xiliary-directed asymmetric alkylation of the imine derived from (R)-(
+)-camphor or (R)-(+)-2-hydroxypinan-3-one. These processes gave diffe
rent enantiomers of gamma-fluoro-alpha-aminobutyric acid via a monomer
ic lithium enolate in the first or a dimeric lithium enolate in the se
cond case, respectively. The enantiomeric excess can be improved by li
thium/magnesium exchange.