A multistage, one-pot procedure mediated by a single catalyst: a new approach to the catalytic asymmetric synthesis of beta-amino acids.
A catalytic asymmetric procedure for the preparation of beta-amino acids (specifically beta-substituted aspartic acid derivatives) is reported. The cinchona alkaloid catalyst benzoylquinine (BQ) mediates up to five distinct steps of a reaction pathway, all in one reaction vessel. The products of this reaction, highly optically enriched beta-substituted aspartic acid derivatives, were prepared from N-acyl-alpha-chloroglycine esters and acid chlorides in the presence of the catalyst. This approach was also amenable to the synthesis of small polypeptides containing beta-substituted aspartic acid units, including a non-natural fragment of the antibiotic lysobactin. The addition of Lewis acids to this system was found to accelerate the rate of specific steps in the reaction pathway. Mechanistic aspects of this reaction, such as imine formation and Lewis acid chelation to the beta-lactam intermediate, were investigated through comparison of IR, NMR, and other physical data.
Hafez
Ahmed M
AM
Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Dudding
Travis
T
Wagerle
Ty R
TR
Shah
Meha H
MH
Taggi
Andrew E
AE
Lectka
Thomas
T
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
D000596:Amino Acids; D007202:Indicators and Reagents