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 α-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.