Computation Aided Investigation of Radical Amination and Hydroxylation via Co(II)- Based Metalloradical Catalysis

Abstract

Recent advancements have witnessed the deployment of radical chemistry for the construction of diverse vital molecular structures. Among these advances, metalloradical catalysis (MRC) has been continuously demonstrated as a practical and unique approach whereby open-shell metal-centered catalysts are exploited to initiate and regulate homolytic radical processes. As stable 15e-metalloradicals, Co(II) porphyrin complexes have been proven effective in activating multifarious precursors to forge unprecedented metal-stabilized organic radicals and are capable of conducting various homolytic processes with well-confined reactivity and selectivity thanks to the support of D2-symmetric chiral porphyrin ligands. Nevertheless, the detailed mechanistic studies of the metalloradical activation of precursors, H atom abstraction (HAA), radical addition, and asymmetric induction have been largely underdeveloped. Therefore, this dissertation mainly focuses on the mechanistic investigations of radical amination and hydroxylation reactions via Co(II)-based MRC with routine experimental methods and powerful computational tools. Chapter 1: Developments on Asymmetric N-Heterobicyclization Reactions of Alkenes via Enantioselective Transition Metal Catalysis. We have viewed recent developments of asymmetric N-heterobicyclization of alkenes rendered by enantioselective transition metal catalysis incorporating first-row, second-row, and third-row transition metals. Chapter 2: Enantioselective Radical N-Heterobicyclization with A New Mode of Asymmetric Induction. We have developed asymmetric radical N-heterobicyclization of allyl sulfamoyl azides with the support of a D2-symmetric chiral bridged amidoporphyrin HuPhyrin ligand. We also revealed a new mode of asymmetric induction that the chirality of a kinetically stable chiral radical center directs the enantioselectivity of the resulting aziridines. The stable chiral radical center was formed from highly challenging enantiofacial selective radical addition and underwent subsequent stereospecific ring closure. Chapter 3: Catalytic Radical N-Heterocyclization by Metalloradical C–H Amination involving 1,7-Hydrogen Atom Abstraction. We have examined intramolecular HAA reaction and pushed its boundary from well-explored 1,5-HAA and 1,6-HAA to unusual 1,7-HAA executed by α-Co(III)-aminyl radicals, which led to the discovery of 1,7-C–H amination and 1,7-HAA triggered indirect 1,5-C–H amination with sulfamoyl azides. Chapter 4: Metalloradical Activation of Alkyl Hydroperoxides for Catalytic Radical C−H Hydroxylation. We have presented comprehensive studies on the metalloradical activation of oxidants, especially cumene hydroperoxide. We have identified ∞-Co(III)-hydroxide cumyloxyl radical species and utilized it for the development of radical C–H hydroxylation with cumyl alcohol as the byproduct.