Total Synthesis of (+)-Cinereain and (-)-Janoxepin through a Fragment Coupling/Retro-Claisen Rearrangement Cascade - Laboratoire de Chimie Théorique Accéder directement au contenu
Article Dans Une Revue Angewandte Chemie International Edition Année : 2022

Total Synthesis of (+)-Cinereain and (-)-Janoxepin through a Fragment Coupling/Retro-Claisen Rearrangement Cascade

Résumé

The total syntheses of (+)-cinereain and (–)-janoxepin, two fungal cyclotripeptides featuring a complex heterocyclic core and interesting phytotoxic and antimalarial activities, have been achieved in a convergent manner. A key step in this synthesis is a one pot cascade initiated by the cyclocondensation of two fragments—a hindered 2-vinylcyclopropane-1-acyl fluoride and an electron deficient cyclic amidine—to release a reactive spiro[2-vinylcyclopropane-1,5'-pyrimidine-4',6'-dione]. This intermediate underwent a spontaneous retro-Claisen rearrangement that was rationalized by DFT calculations. The cascade directly afforded a 2,5-dihydrooxepin-fused heterotricyclic product. In addition, the challenging oxepin ring was finally forged by the palladium-catalyzed β-hydride elimination of an allylic fluoride intermediate. Beyond the development of these original transformations, this work contributes to the first achievement of the asymmetric total syntheses of (+)-cinereain and (–)-janoxepin.

Domaines

Chimie organique
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Dates et versions

hal-03790731 , version 1 (28-09-2022)
hal-03790731 , version 2 (02-02-2023)

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Quentin Ronzon, Wei Zhang, Thomas Charote, Nicolas Casaretto, Gilles Frison, et al.. Total Synthesis of (+)-Cinereain and (-)-Janoxepin through a Fragment Coupling/Retro-Claisen Rearrangement Cascade. Angewandte Chemie International Edition, 2022, 61, pp.e202212855. ⟨10.1002/anie.202212855⟩. ⟨hal-03790731v1⟩
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