Mechanisms and Methods in Redox and Redox-Mediated Reactions Involving Open-Shell Intermediates

Abstract

The application and implication of redox reactions in transition metal chemistry and biological processes have long been established. There has been a resurgence of interest in the application of redox reactions in organic chemistry due to the development of photoredox catalysis, where the combination of a photocatalyst and light is used to generate highly energetic open-shell species that are inaccessible under thermal conditions. Despite the breadth of transformations that have been realized, the transience of the reaction intermediates has resulted in mechanistic ambiguity, precluding rational reaction optimization and development. Chapters 2 to 4 of this dissertation explore the mechanisms of photoredox-mediated nickel-catalyzed carbon-heteroatom cross-coupling reactions. Chapter 2 establishes a thermallysustained Ni(I/III) cycle as a potential productive mechanism for cross-coupling between aryl bromides and alcohols. A deleterious bi-metallic comproportionation, which results in the formation of inactive Ni(II) species, was identified. Chapter 3 shows that a similar Ni(I/III) mechanism is operative in the cross-coupling between aryl iodides and thiols. Guided by these mechanistic insights, we developed light-free analogues of photoredox cross-coupling reactions. Chapter 4 demonstrates that cross-coupling of aryl bromides with amines, alcohols, and carboxylic acids can be realized under strictly thermal conditions when photocatalyst and light are replaced with a substoichiometric amount of Zn metal. Chapter 5 reports the finding that triplet states of ketones selectively abstract amidyl N–H bonds over weaker C–H bonds. This chemoselectivity is due to an asynchronous concerted proton-coupled electron transfer (CPET) reaction, whereby substrates with lower ionization energies preferentially undergo hydrogen atom transfer (HAT). To highlight the utility of this discovery, we show that camphorquinone, a 1,2-diketone, can catalyze the intramolecular hydroamidation of alkenes. Chapters 6 and 7 shift to redox reactions of tetrapyrroles to deliver unusual intermediates of biological significance, arising from redox non-innocence of the macrocycle. In Chapter 6, we demonstrate that cobalt and nickel complexes of a B,C-tetradehydrocorrin, whose state of hydrogenation occupies a seldom-explored chemical space halfway between corrole and corrin, undergoes primarily ligandcentered redox chemistry. Chapter 7 presents the synthesis and characterization of a chlorinphlorin — an elusive dearomatized tetrapyrrole formed through the proton-coupled electron transfer reduction of a chlorin.