α-Amino Acids as Chiral Educts for Asymmetric Products. Amino Acylation with N-Acylamino Acids

Article abstract of DOI:10.1021/ja00410a030

α-N-Acylamino acids have been developed as useful reagents for the preparation of optically pure α-aminoalkylaryl ketones.Protection of the amino group as either the ethoxycarbonyl or benzenesulfonyl derivative allows alanine to serve as an effective educt for the chirally specific synthesis of a variety of structures containing the phenylethylamine backbone.Benzene undergoes Friedel-Crafts acylation with the N-acylalanine acid chloride.Catalyst complexation with oxagenated aromatics, however, prohibits acylation of aryl ethers.An arylmetallo reaction scheme overcomes this problem and also affords regiospecificity not attainable in conventional acylations.As examples, optically pure ephedrines and amphetamines were directly synthesized without recourse to resolution since the chirality of the amino acid educt was entirely conserved throughout the process.