A Meldrum's Acid Based Multicomponent Synthesis of N-Fmoc-isoxazolidin-5-ones: Entry to N-Fmoc-β-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 un-precedented N-Fmoc-isoxazolidin-5-ones. Subsequent chemo-selective reductive cleavage of the N-O bond in the presence of Zn/AcOH allowed a short synthesis of the corresponding N-Fmoc-beta-amino acids.