Stereoselective synthesis of pyrrolidinyl glycines from nitrones: complementarity of nucleophilic addition and 1,3-dipolar cycloaddition

Epimeric pyrrolidinyl glycines, a sort of conformationally constrained α,β-diaminoacids, were stereoselectively prepared using complementary approaches based on nitrone chemistry. Nucleophilic additions to pyrrolidinyl nitrones and 1,3-dipolar cycloadditions of l-serine derived nitrones to form the corresponding hydroxylamines and isoxazolidines, respectively, provided key intermediates for the synthesis of the target compounds. Whereas the nucleophilic addition route afforded the syn adduct, the 1,3-dipolar cycloaddition approach furnished the precursor for the preparation of the corresponding anti compound.