Chemoselective access to substituted butenolides via a radical cyclization pathway: mechanistic study, limits and application

Anne Boussonniere (1) , Romain Beneteau (2) , Jean-Christophe Rouaud (3) , Carole Despiau (3) , Jacques Lebreton (3) , Fabrice Denes (3)

1 IMMM - Institut des Molécules et Matériaux du Mans
2 IICiMed - Cibles et Médicaments des Infections et de l'Immunité
3 CEISAM - Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation

We developed a new approach to gamma-lactols and methylene-gamma-lactols based upon the radical cyclization of aluminium acetals obtained by reduction of alpha-bromoesters with DIBAL-H. The cyclic aluminium acetals resulting from the cyclization process could engage in situ in further functionalization, as illustrated by the Oppenauer-type oxidation to give the corresponding lactones and gamma-butenolides. The preparation of butenolides using this strategy compared favourably with the direct, tin-mediated cyclization of alpha-bromoesters, for which side reactions such as epimerization via [1,5]-HAT processes have been observed.

Mots clés: C–C bond formation; cyclizations; ESOC-19; mechanism; natural product synthesis; radical reactions

Domaines: Chimie

Anne Boussonniere, Romain Beneteau, Jean-Christophe Rouaud, Carole Despiau, Jacques Lebreton, et al.. Chemoselective access to substituted butenolides via a radical cyclization pathway: mechanistic study, limits and application. Pure and Applied Chemistry, 2016, 88 (3), pp.215-225. ⟨10.1515/pac-2015-1203⟩. ⟨hal-02141566⟩