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

Glwadys Gagnot; Vincent Hervin; Eloi P Coutant; Sarah Desmons; Racha Baatallah; Victor Monnot; Yves L Janin

doi:10.3762/bjoc.14.263

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. eCollection 2018.

Authors

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.

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.