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

Glwadys Gagnot (1, 2) , Vincent Hervin (1) , Eloi Coutant (1) , Sarah Desmons (1) , Racha Baatallah (1) , Victor Monnot (1) , Yves Louis Janin (1)

1 Chimie et Biocatalyse
2 UPD5 - Université Paris Descartes - Paris 5

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

Domains: Chemical Sciences; Organic chemistry

Glwadys Gagnot, Vincent Hervin, Eloi Coutant, Sarah Desmons, Racha Baatallah, et al.. Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions. Beilstein Journal of Organic Chemistry, 2018, 14, pp.2846-2852. ⟨10.3762/bjoc.14.263⟩. ⟨pasteur-01972149⟩