Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

  • Beilstein J Org Chem. 2018 Nov 15:14:2846-2852. doi: 10.3762/bjoc.14.263.
Glwadys Gagnot  1  2  3 ,  Vincent Hervin  1  2 ,  Eloi P Coutant  1  2 ,  Sarah Desmons  1  2 ,  Racha Baatallah  1  2 ,  Victor Monnot  1  2 ,  Yves L Janin  1  2
Affiliations
  • 1. Unité de Chimie et Biocatalyse, Département de Biologie Structurale et Chimie, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
  • 2. Unité Mixte de Recherche 3523, Centre National de la Recherche Scientifique, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
  • 3. Université Paris Descartes, Sorbonne Paris Cité, 12 rue de l'École de Médecine, 75006 Paris, France.
PMID: 30498535 DOI: 10.3762/bjoc.14.263
Abstract

We report here on the use of ethyl nitroacetate as a glycine template to produce α-amino esters. This started with a study of its condensation with various arylacetals to give ethyl 3-aryl-2-nitroacrylates followed by a reduction (NaBH4 and then zinc/HCl) into α-amino esters. The scope of this method was explored as well as an alternative with arylacylals instead. We also focused on various [2 + 3] cycloadditions, one leading to a spiroacetal, which led to the undesired ethyl 5-(benzamidomethyl)isoxazole-3-carboxylate. The addition of ethyl nitroacetate on a 5-methylene-4,5-dihydrooxazole using cerium(IV) ammonium nitrate was also explored and the synthesis of Other oxazole-bearing α-amino esters was achieved using gold(I) chemistry.

Keywords
cerium ammonium nitrate; cycloaddition; gold(I) cyclization; α-amino ester; α-nitro esters.
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