Diastereo- and Enantioselective Synthesis of 2-Substituted 1-Aminocyclo­propane-1-Carboxylic Acids. Application to the Synthesis of Protected 2,3-Methano Analogs of Ornithine and Glutamic Acid

Abstract

An enantiodivergent synthesis of protected 2,3-methano amino acid analogs is described. (R)-2-benzyloxyethyloxirane, prepared from (S)-aspartic acid, was reacted with tert-butyl hydrogen malonate and further transformed into an enantiomeric pair of intermediate cyclopropane-fused-lactones, 1-carboxy-2-oxo-3-oxabicyclo[4.1.0]heptane. Each of these enantiomers allowed differentiation of the carboxy functions and generation of a 2-hydroxyethyl group on the cyclopropanes, thus affording access to any or all four stereoisomers. The two-carbon pendant allowed for the direct synthesis of protected 2,3-methano analogs of glutamic acid and ornithine and can be used for other useful transformations.