Enantioselective synthesis of alpha-amino acids from N-tosyloxy beta-lactams derived from beta-keto esters.
A novel synthetic sequence has been developed to convert simple beta-keto esters into enantiomerically enriched alpha-amino acids. The key features of this sequence include the addition of azide to the C3 position of beta-keto ester derived N-tosyloxy-beta-lactams through a concomitant nucleophilic addition/N-O bond reduction reaction, a mild CsF-induced N1 benzylation of alpha-azido monocyclic beta-lactams, the preparation of alpha-keto-beta-lactams through a novel four-step sequence from the corresponding 3-azido-1-benzyl-beta-lactams, and TEMPO-mediated ring expansion of these compounds to the corresponding N-carboxy anhydrides (NCAs). In addition, the synthesis, isolation, and characterization of unusual 3-imino and 3-chloramino-beta-lactams is reported.
Durham
Timothy B
TB
Department of Chemistry and Biochemistry, 251 Nieuwland Science Hall, University of Notre Dame, Notre Dame, Indiana 46556-5670, USA.
Miller
Marvin J
MJ
D000596:Amino Acids / Q000138:chemical synthesis*; D001385:Azetines / Q000737:chemistry*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D004952:Esters / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D014105:Tosyl Compounds / Q000737:chemistry*; D047090:beta-Lactams / Q000737:chemistry*
D000596:Amino Acids; D001385:Azetines; D004952:Esters; D014105:Tosyl Compounds; D047090:beta-Lactams