Co(II)- and Fe(III)-Based Metalloradical Catalysis for Stereoselective Radical Transformations

Abstract

As a conceptually different approach for achieving stereoselective radical reactions, metalloradical catalysis (MRC) utilizes metal-centered radicals as open-shell catalysts for the catalytic generation of metal-stabilized organic radicals as key intermediates to control subsequent one-electron homolytic reactions. Cobalt(II) complexes of porphyrins, as stable 15e-metalloradicals with a well-defined low-spin d7 configuration, have so far dominated the ongoing development of MRC. Through fine-tuning the environments of D2-symmetric chiral amidoporphyrin platform as the supporting ligands, the Co(II)-based metalloradical system can effectively activate various α-aryldiazomethanes to cyclopropanate different dehydroaminocarboxylates under mild conditions, enabling the stereoselective synthesis of chiral cyclopropyl α-amino acid derivatives. Besides, Co(II)-based metalloradical system can homolytically activate both diazomalonates and α-aryldiazomethanes containing different alkene functionalities under mild conditions for effective radical bicyclization, delivering cyclopropane-fused tricyclic chromanones and chromanes, respectively, in high yields with excellent control of bothdiastereoselectivities and enantioselectivities. To broaden MRC beyond the use of Co(II)-based metalloradical catalysts, we illuminate systematic studies that demonstrate the application of a Fe(III)-based system for asymmetric radical transformations. Specifically, we report that five-coordinate Iron(III) complexes of porphyrins with an axial ligand, which represent another family of stable 15e-metalloradicals, are potent metalloradical catalysts for the olefin cyclopropanation with different classes of diazo compounds as well as the intramolecular 1,5-C(sp3)–H amination of various aryl azides, furnishing the valuable cyclopropanes and indolines, respectively, in high yields with high control of stereoselectivities. Mechanistically, a series of experimental investigations, together with DFT computations, offer convincing evidence in support of both Co(II)- and Fe(III)-based MRC and shed light on the details of the stepwise radical mechanism for corresponding catalytic reactions.