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