A Meldrum's Acid Based Multicomponent Synthesis of N‐Fmoc‐isoxazolidin‐5‐ones: Entry to N‐Fmoc‐β‐amino Acids

Alexandra Le Foll (1) , Emmanuel Deau (1) , Emilie Corrot (1) , Laurent Bischoff (1) , Vincent Levacher (1) , Jean-François Brière (1)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

Newly developed conditions allowed a multicomponent KaMC reaction to take place to give previously undescribed N‐Fmoc‐isoxazolidinones. This led to a two‐step synthesis of N‐Fmoc‐β3‐amino acid analogues of the proteinogenic amino acids. A multicomponent Knoevenagel–aza‐Michael cyclocondensation (KaMC) reaction starting from Meldrum's acid has been developed with base‐sensitive N‐Fmoc‐hydroxylamine. The reaction takes place under very mild basic conditions, providing a straightforward synthetic route to various unprecedented N‐Fmoc‐isoxazolidin‐5‐ones. Subsequent chemoselective reductive cleavage of the N–O bond in the presence of Zn/AcOH allowed a short synthesis of the corresponding N‐Fmoc‐β‐amino acids.

Domaines: Chimie

Alexandra Le Foll, Emmanuel Deau, Emilie Corrot, Laurent Bischoff, Vincent Levacher, et al.. A Meldrum's Acid Based Multicomponent Synthesis of N‐Fmoc‐isoxazolidin‐5‐ones: Entry to N‐Fmoc‐β‐amino Acids. European Journal of Organic Chemistry, 2017, 2017 (22), pp.3265-3273. ⟨10.1002/ejoc.201700472⟩. ⟨hal-02046289⟩