A Multistage, One-Pot Procedure Mediated by a Single Catalyst:  A New Approach to the Catalytic Asymmetric Synthesis of β-Amino Acids

A catalytic asymmetric procedure for the preparation of β-amino acids (specifically β-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 reac...

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Bibliographic Details
Published in:Journal of organic chemistry 2003-07, Vol.68 (15), p.5819-5825
Main Authors: Hafez, Ahmed M, Dudding, Travis, Wagerle, Ty R, Shah, Meha H, Taggi, Andrew E, Lectka, Thomas
Format: Article
Language:English
Subjects:
Amino Acids - chemical synthesis
Amino Acids - chemistry
Catalysis
Catalysts: preparations and properties
Chemistry
Exact sciences and technology
General and physical chemistry
Indicators and Reagents
Models, Molecular
Molecular Conformation
Stereoisomerism
Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
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Summary:A catalytic asymmetric procedure for the preparation of β-amino acids (specifically β-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 β-substituted aspartic acid derivatives, were prepared from N-acyl-α-chloroglycine esters and acid chlorides in the presence of the catalyst. This approach was also amenable to the synthesis of small polypeptides containing β-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 β-lactam intermediate, were investigated through comparison of IR, NMR, and other physical data.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo034150e