Synthesis of L-4,4-difluoroglutamic acid via nucleophilic addition to a chiral aldehyde

Fluorine-containing derivatives of amino acids are assuming increasing importance as probes of biological function and enzyme mechanism. We now report a new, flexible route to enantiomerically pure L-4,4-difluoroglutamic acid that exploits the addition of difluorinated nucleophiles to configurationally stable alpha-aminoaldehydes. Conversion of the difluorinated adducts to L-4,4-difluoroglutamic acid can be accomplished in three steps by Barton-McCombie dehydroxylation and acid hydrolysis.