A Diastereo- and Enantioselective Synthesis of α-Substituted syn-α,β-Diamino Acids

• Published in: Journal of the American Chemical Society Vol. 130; no. 18; pp. 5866 - 5867
• Main Authors: Singh, Anand, Johnston, Jeffrey N
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.05.2008; Amer Chemical Soc
• Subjects: Acetates - chemistry; Amino Acids, Diamino - chemical synthesis; Amino Acids, Diamino - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; Imines - chemistry; Phenylalanine - analogs & derivatives; Phenylalanine - chemical synthesis; Physical Sciences; Science & Technology; Stereoisomerism; ASYMMETRIC-SYNTHESIS; AMINO-ACIDS; DIAMINATION; CHIRAL PROTON CATALYSIS; ALPHA,BETA-DIAMINO ACIDS; DERIVATIVES; QUATERNARY
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja8011808

Highly diastereo- and enantioselective additions of substituted α-nitroesters to imines have been developed. High diastereoselection relies on the finding that the combination of chiral proton catalyst 2b and α-nitro aryl esters bearing 2,6-disubstitution combine to raise substrate-controlled diastereoselection to >20:1 in favor of the syn diastereomer. Furthermore, the chiral catalyst provides enantioselection to the 99% level through control of the addition step in which the azomethine π-faces are differentiated. The bifunctional chiral protic acid catalyst enables these reactions to proceed without separate preactivation of either substrate, leading to a straightforward synthetic protocol for the formation of α,β-diamino phenyl alanine derivatives.