Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

Eloi Coutant (1) , Vincent Hervin (1) , Glwadys Gagnot (1) , Candice Ford (2) , Racha Baatallah (1) , Yves Louis Janin (1)

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

We have explored here the scope of the age-old diethyl malonate-based accesses to α-amino esters involving Knoevenagel condensations of diethyl malonate on aldehydes, reductions of the resulting alkylidenemalonates, the preparation of the corresponding α-hydroxyimino esters and their final reduction. This synthetic pathway turned out to be general although some unexpected limitations were encountered. The synthetic modifications of some of the intermediates - using Suzuki-Miyaura coupling or cycloadditions - before undertaking the oximation step - provided accesses to further α-amino esters. Moreover, other pathways to α-hydroxyimino esters were explored including an attempt to improve the cycloadditions between ethyl β-bromo-α-hydroxyiminocarboxylate and various alkylfuranes.

Keywords: Suzuki–Miyaura; [2 + 3] cycloadditions; [2 + 4] cycloadditions; nitrosoacrylate; Knoevenagel; α-amino ester; α-hydroxyimino ester

Domains: Chemical Sciences; Organic chemistry

Eloi Coutant, Vincent Hervin, Glwadys Gagnot, Candice Ford, Racha Baatallah, et al.. Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate. Beilstein Journal of Organic Chemistry, 2018, 14, pp.2853-2860. ⟨10.3762/bjoc.14.264⟩. ⟨pasteur-01972143⟩