Iron(II)-Catalyzed Radical [3 + 2] Cyclization of N-Aryl Cyclopropylamines for the Synthesis of Polyfunctionalized Cyclopentylamines.

Abstract

A facile iron(II)-catalyzed radical [3 + 2] cyclization of N-aryl cyclopropylamines with various alkenes to access the structurally polyfunctionalized cyclopentylamine scaffolds has been developed. Using low-cost FeCl2·4H2O as catalyst, N-aryl cyclopropylamines could be utilized to react with a wide range of alkenes including exocyclic/acyclic terminal alkenes, cycloalkenes, alkenes from the natural-occurring compounds (Alantolactone, Costunolide), and known drugs (Ibuprofen, l-phenylalanine, Flurbiprofen) to obtain a variety of cyclopentylamines fused with different useful motifs in generally good yields and diastereoselectivities. The highlight of this protocol is also featured by no extra oxidant, no base, EtOH as the solvent, gram-scale synthesis, and further diverse transformations of the synthetic products. More importantly, an iron(II)-mediated hydrogen radical dissociation pathway was proposed based on the mechanism research experiments.