Authors: Wesley Pein
Source: Deep Blue (University of Michigan) (article, 2021-01-01)
Field: Chemistry — Organic Chemistry

Design and Synthesis of Nickel N-Heterocyclic Carbene Catalyst Systems and Their Application in the Cross-Coupling of Silyloxyarenes The invention of transition-metal catalyzed cross-coupling reactions has fundamentally changed how chemists approach the synthesis of small molecules. Moreover, the ability to perform reactions catalytically while employing Earth abundant first row transition-metals has had positive impacts regarding sustainability. In addition to environmental considerations, first row transition-metals, like nickel, have been found to possess reactivity that is complementary to metals like palladium, which has implications for how the metal performs in the various elementary steps of catalytic processes. These insights have arisen from the study, design, and development of nickel catalyst systems, which have propelled the invention of catalytic strategies for the formation of a wide array of C‒C and C‒heteroatom bond forming reactions. The nature of reaction development and catalyst design are intimately related as achieving the development of novel bond forming reactions relies upon innovative advances that reduce the limitations associated with existing catalyst systems to provide enhanced performance, or to make the catalysts, themselves, more accessible. An account of these efforts in the context of C‒O bond functionalization and air-stable, discrete nickel(0) (Ni(0)) n-heterocyclic carbene (NHC) catalysts are described, herein. Chapter 1 is largely oriented towards the utility of phenol derivatives as electrophilic coupling partners with low-reactivity C‒O bonds being of main interest. The challenges regarding the activation of these low-reactivity C‒O bonds is discussed, as well as current strategies to overcome their inherently low-reactivity. Although low-reactivity C‒O bonds are challenging to activate, their functionalization is of import as possessing electrophilic coupling partners that range in reactivity enables highly selective sequential couplings, resulting from leveraging the orthogonal reactivity of each electrophile. Chapter 2 chronicles the utility of aryl boronic acids in organic synthesis, with particular attention paid to their role in cross-coupling reactions. The synthesis of these compounds spanning from traditional approaches to modern techniques, which includes the state of the art in the borylation of low-reactivity C‒O bonds. The limitations of these strategies are covered and the development of a borylation of silyloxyarenes is described along with synthetic demonstrations that highlight the ability of silyloxyarenes to be used orthogonally to other electrophiles. Chapter 3 entails the advantages of catalysis, and the transition metal catalysts we rely upon to mediate these processes, with special attention to nickel, have evolved. For the purposes of this dissertation, nickel catalysts have been categorized as 1) Ni(II) salts, 2) discrete Ni(II) pre-catalysts, 3) Ni(0) pre-catalysts, 4) air-stable Ni(0) pre-catalysts, and 5) discrete air-stable Ni(0) pre-catalysts. The advantages and disadvantages, activation strategies, and synthesis of each category are described in detail. Preliminary work regarding progress towards the synthesis of an air-stable, discrete Ni(0) NHC complex from nickel (II) (Ni(II)) precursors and NHC salts is described. Nickel ; Carbene ; Catalysis ; Coupling (piping) ; Combinatorial chemistry ; Chemistry ; Materials science ; Organic chemistry ; Metallurgy Catalytic Cross-Coupling Reactions ; N-Heterocyclic Carbenes in Organic and Inorganic Chemistry ; Asymmetric Hydrogenation and Catalysis