New advances in stereoselective Meyers’ lactamization. Application to the diastereoselective synthesis of β-substituted oxazoloazepinones

Alexis Bouet (1) , Sylvain Oudeyer (1) , Georges Dupas (1) , Francis Marsais (1) , Vincent Levacher (1)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

A stereoselective approach to the preparation of 7,5-fused bicyclic lactams based on Meyers’ lactamization is presented. The lactamization step is conducted at 0 °C with 6-oxohexanoic acid 1 and with various chiral aminoalcohols in the presence of 2-fluoro-1-ethylpyridinium tetrafluoroborate (FEP) as an activating agent. Under these mild conditions, bicyclic lactams 2–4 were obtained in satisfactory yields and diastereoselectivities up to 95%. To account for the high level of diastereoselection, the mechanistic aspects of Meyers’ lactamization were investigated by means of in situ infrared spectroscopy. Finally, the lactam enolate derived from 2 was subjected to reaction with various electrophiles, furnishing the corresponding β-substituted oxazoloazepinones 5–9 in good yields (up to 86%) and in moderate to excellent diastereoselectivities ranging from 27% to 95% de.

Domains: Chemical Sciences; Organic chemistry

Alexis Bouet, Sylvain Oudeyer, Georges Dupas, Francis Marsais, Vincent Levacher. New advances in stereoselective Meyers’ lactamization. Application to the diastereoselective synthesis of β-substituted oxazoloazepinones. Tetrahedron: Asymmetry, 2008, 19 (20), pp.2396-2401. ⟨10.1016/j.tetasy.2008.10.014⟩. ⟨hal-02278757⟩