Late Transition Metal Pre-Catalysts for the Hydrogenation of Carbonyl-Containing Substrates

Thesis (Ph.D.)--University of Washington, 2018This thesis describes efforts to develop new pre-catalysts for the hydrogenation of challenging carbonyl substrates, including esters and amides. We seek to understand the mechanisms by which these catalysts operate, and to use this understanding to rationally design new pre-catalysts, as well as to identify complexes that can operate in a multi-catalyst cascade for the stepwise hydrogenation of CO2 to methanol. Chapter One outlines the motivations for this work. The history and development of ester and amide hydrogenation pre-catalysts is discussed, as well as the rationale and precedent for using catalytic cascades to synthesize methanol from CO2. Chapter Two explores the hydrogenation of lactone substrates by a bipyridine-supported half-sandwich iridium complex. This is a rare example of an ester hydrogenation pre-catalyst that is tolerant to the addition of acid. Chapter Three describes computational studies into the mechanism of ester and amide hydrogenation by aliphatic pincer-supported complexes of iron and ruthenium. Subtle disparities in the hydrogenation mechanism between ester and acid model substrates highlight the influence of substrate identity on reactivity. We find that, surprisingly, the highest calculated barrier in amide hydrogenation involves the rupture of the hemiaminal intermediate, rather than initial hydrogenation of the carbonyl group. Chapter Four describes the hydrogenation of simple formate substrates by PCP- and POCOP-supported complexes of iridium. The crucial roles of acid additives in pre-catalyst activation and catalyst deactivation pathways are explored. These efforts showcase the limitations of ionic ester hydrogenations and illustrate how understanding the reactivity of metal complexes enables rational pre-catalyst selection and design. Finally, in Chapter Five, these iridium pre-catalysts are successfully incorporated into cascade systems for the conversion of CO2 to methanol