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Syntheses ofγ-fluoro-α-amino acids

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Summary

Methods for the synthesis of racemic and optically active title compounds are presented. Key step of these four-step procedures is the alkylation with 1-bromo-2-fluoroalkanes of glycine-ester-derived imines in anhydrous medium using lithium diisopropylamide as a base at low temperature or phase transfer catalyzed alkylation with 50% NaOH and triethylbenzylammoniumchloride as the phase transfer catalyst, respectively. Subsequent three-step deprotection gave the free acids in 13–33% overall yield. Deracemization ofγ-fluoro-α-aminobutyric acid methyl and ethyl esters withα-chymotrypsin was shown to give the (−)-enantiomers of the esters and (+)-γ-fluoro-α-aminobutyric acid in >98% ee, while from thetert-butylester the opposite stereochemical result was observed giving the (−)-acid with 88% ee. Optically activeγ-fluoro-α-amino acids were synthesized alternatively by phase transfer catalysis with N-benzyl-cinchonium chloride or using an auxiliary-directed asymmetric alkylation of the imine derived from (R)-(+)-camphor or (R)-(+)-2-hydroxypinan-3-one. These processes gave different enantiomers ofγ-fluoro-α-aminobutyric acid via a monomeric lithium enolate in the first or a dimeric lithium enolate in the second case, respectively. The enantiomeric excess can be improved by lithium/magnesium exchange.

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Authors and Affiliations

  1. Organisch-Chemisches Institut, Universität Münster, Corrensstraße 40, D-48149, Münster, Germany

    G. Haufe & S. Kröger

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  1. G. Haufe
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  2. S. Kröger
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Haufe, G., Kröger, S. Syntheses ofγ-fluoro-α-amino acids. Amino Acids 11, 409–424 (1996). https://doi.org/10.1007/BF00807945

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