Enantiodivergent Synthesis of (+)- and (-)-Pyrrolidine 197B. Synthesis of trans-2,5-Disubstituted Pyrrolidines via Intramolecular Hydroamination

Abstract

A highly efficient diastereoselective iron(III)-catalyzed intramolecular hydroamination/cyclization reaction involving - substituted amino alkenes is described. Thus, enantiopure trans-2,5- disubstituted pyrrolidines and trans-5-substituted proline derivatives are synthesized by means of the combination of enantiopure starting materials, easily available from L--amino acids, with sustainable metal catalysts such as iron(III) salts. The scope of this methodology is highlighted in an enantiodivergent approach to the synthesis of both (+)- and (-)-pyrrolidine 197B alkaloids from L-glutamic acid. In addition, a computational study was also carried out to gain insight into the complete diastereoselectivity of the transformation.