Vlasov Simulation with FARSIGHT and Unlimited Photon Acceleration

Abstract

Metal-catalyzed C–H functionalization has revolutionized the field of synthetic chemistry with widespread implementation in the synthesis of pharmaceuticals and agrochemicals. In the past few decades, seminal work from numerous groups across the fields of organic and inorganic chemistry have demonstrated that noble metals generally serve as the most efficient catalysts. While these reactions are mechanistically well understood, the noble metal catalysts are often prohibitively expensive for large scale applications. Recently, base-metal catalysts like nickel and copper have been shown to functionalize inert C–H bonds in aminoquinoline directed systems. However, these remain mechanistically less understood than the noble metal analogs. Reactive high-valent nickel intermediates have been proposed but not isolated nor spectroscopically observed. Hence, the major focus of this thesis was to synthesize, isolate, and characterize structurally relevant nickel complexes on the aminoquinoline scaffold and to test their catalytic relevance. Chapter 1 describes a general overview of aminoquinoline directed C–H functionalization reactions with nickel (II) catalysts. This chapter highlights the general mechanistic scenarios for these reactions in which high-valent (NiIII and NiIV) species have been proposed as reactive intermediates. Chapter 2 contains experimental details describing attempts to isolate the aminoquinoline -alkyl and -aryl nickelacycle complexes via C–H functionalization. Under certain conditions formation of the target nickelacycles is observed by NMR spectroscopy, but all attempts at isolation were unsuccessful owing to poor conversion. Other routes were pursued to isolate these nickelacycle complexes, and ultimately a decarbonylation strategy proved successful to isolate a phosphine bound NiII species on both the alkyl and aryl scaffolds. Oxidation studies on the isolated phosphine complexes predominantly lead to ligand-based reactivity i.e., C–P bond formation. Chapter 3 describes exchange of the phosphine ligands for more oxidatively stable pyridine ligands, which eliminated ligand-based reactivity upon oxidation. Stoichiometric oxidation of these pyridine ligated NiII complexes with I2 resulted in C(sp3)–N and C(sp2)–I bond-forming reactions. Furthermore, these complexes were shown to be catalytically relevant as noted by turnover under catalytic conditions of the aforementioned bond-forming reactions. Chapter 4 describes the oxidation of pyridine ligated NiII complexes to form and isolate high-valent NiIII complexes, which have been previously proposed in the literature as reactive intermediates in C–H functionalization catalysis. Electrochemical studies informed the appropriate choice of one-electron oxidants for isolation of these NiIII complexes. The isolated complexes were shown to be catalytically inert species under catalytic reaction conditions unlike the previously isolated NiII species in Chapter 3. An aryl-aryl coupling reaction was also discovered from the isolated NiIII complex on the aryl scaffold. Chapter 5 describes general strategies employed in attempts to isolate NiIV complexes with these aminoquinoline bound nickelacycles. These involve the use of strong two-electron oxidants and polydentate ligands to access and stabilize NiIV intermediates. The synthesis, isolation, characterization of the polydentate NiIII complexes is described, and general results from the oxidation reactions are summarized. Although the isolation of a NiIV complex was unsuccessful on this scaffold, based on the findings, some general guiding principles have been proposed as future directions.