One‐Pot Synthesis of Metastable 2,5‐Dihydrooxepines Through Retro‐Claisen Rearrangements: Methods and Applications

Wei Zhang (1, 2) , Emmanuel Baudouin (3) , Marie Cordier (4) , Gilles Frison (4) , Bastien Nay (1)

1 DCSO - Laboratoire de synthèse organique
2 MCAM - Molécules de Communication et Adaptation des Micro-organismes
3 LBD - Laboratoire de Biologie du Développement [IBPS]
4 LCM - Laboratoire de chimie moléculaire

A one-pot methodology to synthesize metastable bicyclic 2,5-dihydrooxepines from cyclic 1,3-diketones and 1,4-dibromo-2-butenes is reported, through the retro-Claisen rearrangement of syn-2-vinylcyclopropyl diketone intermediates. High-level quantum chemical calculations were performed to understand the reaction selectivity and mechanisms towards [1,3] or [3,3]-sigmatropic rearrangements, highlighting the crucial influence of temperature in close relation to experimental results. The reaction was successfully applied to a short protecting group-free total synthesis of radulanin A, a natural 2,5-dihydrobenzoxepine, featuring an unprecedented aromatization strategy of the transient bicyclic 2,5-dihydrooxepine. We demonstrate for the first time the strong herbicidal potential of this natural product.

Domaines: Chimie organique; Chimie; Chimie théorique et/ou physique

Wei Zhang, Emmanuel Baudouin, Marie Cordier, Gilles Frison, Bastien Nay. One‐Pot Synthesis of Metastable 2,5‐Dihydrooxepines Through Retro‐Claisen Rearrangements: Methods and Applications. Chemistry - A European Journal, 2019, ⟨10.1002/chem.201901675⟩. ⟨hal-02135526⟩