Enantioselective intramolecular michael addition of nitronates onto conjugated esters: access to cyclic gamma-amino acids with up to three stereocenters.
A highly stereoselective synthesis of conformationally constrained cyclic gamma-amino acids has been devised. The key step involves an intramolecular cyclization of a nitronate onto a conjugated ester, promoted by a bifunctional thiourea catalyst. This methodology has been successfully applied to generate a variety of gamma-amino acids, including some containing three contiguous stereocenters, with very high diastereoselectivity and excellent enantioselectivity. It is postulated that an interaction that is key to the success of the process is the simultaneous coordination of the thiourea functionality to both the conjugated ester and the nitronate. Finally, the synthetic utility of these compounds is demonstrated in the synthesis of two dipeptides derived from the C- and N-termini.
Nodes
William J
WJ
School of Pharmacy and Department of Chemistry, University of Reading, Whiteknights, Reading, Berks RG6 6AD, UK.
Nutt
David R
DR
Chippindale
Ann M
AM
Cobb
Alexander J A
AJ
D000598:Amino Acids, Cyclic / Q000138:chemical synthesis*; D004952:Esters / Q000737:chemistry; D009589:Nitrogen Oxides / Q000737:chemistry*; D013237:Stereoisomerism
D000598:Amino Acids, Cyclic; D004952:Esters; D009589:Nitrogen Oxides; C015388:nitrones