Enantioselective Intramolecular Michael Addition of Nitronates onto Conjugated Esters: Access to Cyclic γ-Amino Acids with up to Three Stereocenters

Nodes, W., Nutt, D. R., Chippindale, A. M. ORCID: https://orcid.org/0000-0002-5918-8701 and Cobb, A. J. A. (2009) Enantioselective Intramolecular Michael Addition of Nitronates onto Conjugated Esters: Access to Cyclic γ-Amino Acids with up to Three Stereocenters. Journal of the American Chemical Society, 131 (44). pp. 16016-16017. ISSN 0002-7863 doi: 10.1021/ja9070915

Abstract/Summary

A highly stereoselective synthesis of conformationally constrained cyclic γ-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 γ-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.