A large part of chemistry is driven by localized electric fields between charged species, for example when an electron is exchanged in between a redox reaction pair, or a nucleophile attacks a positively charged part of a molecule. Ideally, scientists try to not only observe and understand these processes, but also gain control over them in order to steer reactions in a certain direction. In this thesis, the use of electric fields to influence reactions was studied in several reactive systems, including various chemical environments and two different ways to apply electric fields. The first part of this thesis work investigates the impact of an electric field generated by a focused laser pulse of nonresonant radiation, which is referred to as photon catalysis. The second part explores other ways to apply electric fields to chemical reactions: on the surface of microdroplets, and by voltage applied to a semiconductor on the nanoscale. Chapter 1 introduces the concept of photon catalysis. It outlines how a focused laser pulse of nonresonant radiation can act as a catalyst through its strong electric field: no photons are used up or changed in the interaction, but upon the application of the electric field laser, particular reaction pathways can be favored over others, resulting in a net change in the reaction dynamics. Furthermore, Chapter 1 lays the groundwork for the following chapters by characterizing the electric field generated by a nanosecond laser pulse, and by describing the experimental setup for photon catalysis on gas-phase reactions. It also presents the first studies on photon catalysis carried out in this lab, and defines which properties of a reactive system render it a good candidate to showcase the photon catalytic effect. Chapter 2 shows how the application of a nonresonant, focused laser pulse of infrared radiation changes the outcome of the dissociation of deuterium iodide. Depending on the excitation wavelength, deuterium iodide can dissociate via different reaction pathways after the excitation, yielding a product mix of two distinct deuterium (D) species. The relative product ratio at which these two species are formed is changed in the presence of the electric field supplied by the infrared laser pulse, indicating a change in the reaction dynamics. The magnitude and the direction of change are dependent on the excitation wavelength. The underlying mechanism for the change is explored both experimentally and theoretically, and there is an agreement that the observed effect is rather caused by an AC-Stark shift of the potential energy surfaces, than by molecular alignment of the reactants. Chapter 3 continues to explore photon catalysis by extending the studies to a more complex molecule, phenol. The photodissociation of phenol along the OH bond involves two well-characterized dissociation pathways, which are populated to different degrees depending on the excitation wavelength. The reaction products are phenoxy radicals and hydrogen atoms of characteristic speeds. In this study, two features in the potential energy landscape are probed: a conical intersection, and the minimum energy threshold that it requires to dissociate the molecule. Similarly to lowering an activation barrier, the conical intersection is lowered by the electric-field induced Stark-shift, generated by the focused, nonresonant laser pulse. Therefore, the pathway that lies higher in energy is opened up wider than under field-free conditions. The dissociation origin experiences a smaller Stark-shift, yet allows for phenol dissociation at a wavelength that is not sufficient to yield any dissociation under field-free conditions. The postulated mechanism is supported by theoretical calculations. Chapter 4 transfers the concept of photon catalysis from gas-phase reactions to solution-phase systems. It outlines the changes and challenges of the chemical environment that reactants and the laser beam face, and proposes potential experimental setups. Following successful setup development, the impact of the electric field on the photoisomerization of stilbene is investigated: When a solution of cis-stilbene (CS) in cyclohexane is irradiated with ultraviolet photons, photoisomerization to trans-stilbene (TS) is promoted, and an irreversible ring-closure reaction to form phenanthrene (PH) is observed. At wavelengths around the red absorption onset, the TS formation is increased by the application of the electric field laser, and at excitation wavelengths in the center of the absorption range, the CS is increasingly converted to both TS and PH. This change is partially due to local heating in the reaction solution, which can be subtracted as background at the edge wavelengths, but is overwhelming at the absorption center. Multiphoton processes are not observed in measurable amounts. The end of this chapter highlights the promising perspectives for further use and development of photon catalysis in condensed-phase systems. Chapter 5 approaches a different application of electric fields in chemistry: the conversion of low-value polycyclic aromatic hydrocarbons to compounds with higher petrochemical utility. A new method to obtain higher conversion rates is proposed, which involves two ways of how electric fields can be applied in chemical reactions. First, the reactant solution is sprayed with a sheath gas from a small nozzle, generating micron-sized liquid droplets that exhibit strong electric fields on the surface, enhanced by an electric double layer if the solution contains water. Second, these droplets subsequently hit immobilized anatase nanoparticles, which are charged with 2 kV, and continuously wetted. The applied voltage results in an electron-hole separation, where the oxidative hole converts the water to highly reactive hydroxy radicals. The combination of the electric field on the microdroplet surface with the hydroxy radicals is required to obtain high degradation yields of the sample molecule rubrene. The method is validated on selected other molecules as well.

Catalytic methods for C(sp3)--H amination are enabling technologies for both the synthesis and late-stage diversification of myriad organic molecules. Contemporary challenges that propel future development of such processes are presented by complex substrates approximating the architectures found in natural products along with polar, functional group-rich active pharmaceutical and agrochemical ingredients. In our efforts to address these limitations, we have established a catalytic system for C--H amination that markedly advances the ability of chemists to efficiently introduce nitrogen into molecules of different structural types. The discovery of pivalonitrile (t-BuCN) as a differential solvent for Rh-catalyzed intermolecular amination of C(sp3)--H bonds and phenyl sulfamate (PhsNH2) as a nitrene precursor has enabled efficient functionalization of a wide variety of complex molecule substrates including natural products and active pharmaceutical ingredients (APIs). Although limitations remain with oxidatively labile functional groups, including basic amines, our disclosure represents a definitive leap forward in the state-of-the-art for C--H bond oxidation. Mechanistic data strongly implicate a pathway for catalyst decomposition that initiates with solvent oxidation, thus providing rationale for the marked influence of pivalonitrile on this reaction process. The phenyl sulfamate nitrogen source can be unmasked under mild conditions using pyridine and water to unveil the corresponding primary amine products. Additionally, through amination of bromoalkane and mesyloxalkane substrates, SN2 cyclization can afford azetidines and other saturated azacycles in good to excellent yield. In pursuit of alternative, modular methods for the installation of sulfamate and sulfamide groups, we have developed pentafluorophenyl sulfamate (PfpsNH2) and trichlorphenyl sulfmatate (TcpsNH2) as bench-stable, versatile reagents for sulfamoylation of alcohol and amine nucleophiles to generate N-unsubstituted sulfamates and sulfamides. This type of 'click' reaction should find widespread use in academic and industrial labs.

Copper active sites catalyze a wide range of oxygen reactions in biology. While the majority of enzymes utilize Cu(I) to directly reduce O2, two families of enzymes instead use mononuclear Cu(II) sites to enhance the reactivity of organic molecules toward O2, which is a process known as Cu(II)-substrate activation. These are quercetin 2,4-dioxygenase (QD), which catalyzes the dioxygenation of flavones, and amine oxidase (AO), which utilizes Cu(II) to activate an active site tyrosine residue for a 6e- oxidation reaction to form its redox active cofactor, TPQ. Given the negligible reactivities of the free substrates and of Cu(II) toward O2, mechanistic proposals for these reactions invoke Cu(I)-substrate radical character as the basis for these sites reactivities. In order to evaluate these as well as alternate mechanisms, the electronic structures of these enzymes were first determined along with a number of closely related model complexes with combination of spectroscopic, computational, and kinetic techniques. These experimentally determined electronic structures were then used to calibrate DFT calculations to generate accurate electronic structure descriptions of the QD and AO enzyme-substrate complexes. Finally, these calculated active site models were used to evaluate possible mechanisms for their reactions with O2. Chapter 2 details the electronic structures of the QD enzyme-substrate complexes and a number of related model complexes. Unlike QD, these model complexes decrease the reactivity of bound flavones, and differ from QD primarily by their flavone binding mode. In the model complexes, the flavones bind to the metal in a bidentate fashion with the metal coordinated within the flavone molecular plane, while in QD the flavones bind monodentate with the metal out of the flavone molecular plane. This leads to considerably different electronic structures between the QD enzyme-substrate complexes and the model complexes. In the model complexes, flavone binding to Cu(II) primarily stabilizing the σ-bonding flavone orbitals, while in QD, flavone binding to Cu(II) stabilizes the flavone π-bonding molecular orbitals. Both types of binding geometries lead to moderate flavone-Cu(II) covalencies, but minimal ground state Cu(I)-flavone radical character and no thermally accessible charge transfer states. Calculations of the free flavone, model complex, and enzyme reaction mechanisms show that the models and enzyme increase the barrier for the reaction of O2 directly on the flavone by increasing the flavone ionization potentials. Given the low energy barrier for the O2 reaction performed by the enzyme, the active site Cu(II) must play a direct role in activating O2. In chapter 3, geometric and electronic structures are provided for the Cu(II)-loaded, pre-biogenesis AO active site (preAO). It was first shown that Cu(II) loading into the active site is slow, and that a second, non-catalytic, kinetically favored Cu(II) binding site affects the rate of Cu(II)-active site binding. Cu(II) stably binds to the active site, and prior to the biogenesis reaction is in a thermal equilibrium between two forms. The major form is entropically favored, and is a 4-coordinate site with 3-histidines and a hydroxide as the Cu(II) ligands. The minor form (which is present at 7% at room temperature) is a 5-coordinate site with three histidines, water, and the tyrosinate which processes to TPQ as its ligands. We showed that the minor form is active in biogenesis, and furthermore that this form has a low covalency interaction between the tyrosinate and Cu(II), no discernible Cu(I)-tyrosyl radical character, and no thermally accessible Cu(I)-tyrosyl radical states. Thus, the O2 activation step in biogenesis is performed by a fairly ionic Cu(II)-tyrosinate site. Chapter 4 provides spectroscopic and kinetic analyses of the AO biogenesis reaction. Four intermediates are observed during the biogenesis reaction. First, an intermediate with a 350nm absorbance band grows at the same rate that the minor, preprocessed form disappears. This band has an ε of 2800M-1cm-1, O2-dependent growth, and an O2-independent decay that allow its possible assignment as a dopaquinone intermediate. The 350nm species decays at a rate that is commensurate with the growth of a second intermediate, which has a set of 390nm/410nm bands in absorbance and an organic radical signal in EPR. The small amount of this intermediate that builds up during the biogenesis reaction places it as the minor species of an equilibrium with a Cu(II) form of the active site, and allows its likely assignment as the Cu(I)-organic radical form of trihydroxyphenylalanine, a species which undergoes a 2e- oxidation by reducing a molecule of O2 to H2O2 to become TPQ. Finally, a 330nm band forms at a rate that is commensurate with TPQ formation and then decays at a similar rate. Possible assignments for this species are discussed. A comprehensive kinetic model for the biogenesis reaction provides a lower limit of 1.5s-1 for the initial O2 activating step, giving its energy barrier an upper limit of ∆G^‡=11kcal/mol. This provides a key bench mark for evaluating possible mechanisms of tyrosinate activation for O2 reaction by a Cu(II) center.

Hydrogen peroxide (H2O2) is a highly valuable chemical with wide range of applications in industry such as paper bleaching, textile manufacturing and environmental protection. Currently, the industrial synthesis of H2O2 is through an energy intensive anthraquinone process, which requires large-scale and complex infrastructure. Electrochemical synthesis of H2O2 from oxygen reduction offers an attractive alternative route for onsite applications, while the efficiency of this process greatly depends on identifying cost-effective catalysts with high activity and selectivity. As several classes of catalysts have been reported or proposed by theory to be good candidates of the targeted reaction, here we focus our attention upon a metal-organic framework (MOF) and high-performance carbon catalysts for the perspective of both fundamental understanding and the high cost-efficiency. Catalytic systems whose properties can be systematically tuned via changes in synthesis conditions are highly desirable for applications in catalyst design and optimization, namely, the 2D conductive metal--organic framework (MOF) with M-N4 units (M = Ni, Cu) and a hexaaminobenzene (HAB) linker as a catalyst for the oxygen reduction reaction (ORR). By varying synthetic conditions, we synthesized two Ni-HAB catalysts with different crystallinities, resulting in a catalytic system with variable electrical conductivity, electrochemical activity and stability. We show that crystallinity has a positive impact on conductivity and demonstrate that this improved crystallinity/conductivity improves the ORR performance of our model system.

Carbon-carbon and carbon-nitrogen bonds are some of the most common motifs in organic molecules and as a result, the invention of new methods for selectively forming these bonds is highly important. The first half of this thesis describes the discovery of two novel and unexpected carbon-carbon bond forming reactions, and also includes a review on the unique chemistry of geminal and vicinal bis(sulfones). The second half of this work deals with enantioselective carbon-nitrogen bond formation, and describes the development of two transition metal-catalyzed asymmetric allylic alkylation reactions. It also contains a review on annulative allylic alkylation reactions between dual electrophiles and dual nucleophiles and their applications in complex molecule synthesis.

Polycyclic conjugated hydrocarbons (PCHs) containing four-membered cyclobutadienoids (CBDs) are of great fundamental and technical interest due to the antiaromaticity brought by CBD circuits. Synthetic accessibility of such molecules, however, has been challenging and limited in scope, thus hampering the exploration and understanding of such systems. In this thesis, a versatile and efficient synthetic strategy was developed to access a large variety of CBD-containing PCHs with variable carbon structures, electronics, and topologies via catalytic arene-(oxa)norbornene annulation (CANAL) from readily accessible aryl bromides and oxanorbornenes (oNBEs). This new synthetic capability opens a myriad of opportunities for systematic investigation into CBD antiaromaticity as well as the potential applications of CBD-PCHs. With this facile method, we proposed and synthesized a series of unprecedented [3]naphthylene regioisomers, and found the regioconnectivity of [3]naphthylenes strongly affects the degree of local antiaromaticity and aromaticity for the fused CBD and naphthalenoid, respectively. Further, the C-C bond activation of CBD units was demonstrated with unsubstituted V-shaped [3]naphthylene to yield helical structures. In addition, we designed and efficiently synthesized a novel CBD-containing acene analogues, dinaphthobenzo-[1,2:4,5]dicyclobutadiene (DNBDCs), with strong antiaromaticity of the CBD units. This design also features orthogonally tunable electronic properties and molecular packing, which resulted in good device performance in organic field effect transistors.

Anthropogenic climate change will cause irreparable damage to the environment if measures are not taken to abate the emissions of CO2. One way to drive emissions down is to valorize CO2 by using it as a carbon source for the synthesis of chemical feedstocks. The development of new technologies that produce chemicals from CO2 in a cost competitive and efficient way could put market pressure on existing fossil-derived petrochemicals and incentivize the capture of CO2 from concentrated point sources such as power plants. One attractive strategy for CO2 valorization is to use renewable energy to power the aqueous electrochemical reduction of CO2 and H2O to generate valuable C2+ chemical feedstocks such as ethylene, ethanol, propanol, and acetate. Unfortunately, the spontaneous reaction of CO2 and HO-- to form HCO3-- and CO32-- impedes the optimization of these systems. While the operation of CO2 reduction cells with alkaline electrolytes results in low total cell voltages, the super stoichiometric consumption of MOH in these systems represents a significant energy penalty. Furthermore, only low single-pass conversions have been achieved for CO2 electrolysis resulting in dilute product streams that are energy intensive to purify. Deconstructing CO2 reduction into two separate electrochemical steps may offer a path to overcome the challenges posed by direct electrochemical CO2 reduction. In this two-step process, CO2 is first converted to CO with a high temperature solid oxide electrolysis cell (SOEC), in which the reaction of CO2 and HO-- is avoided. The CO is subsequently reduced in a separate electrochemical cell to generate C2+ chemical feedstocks. While SOECs have recently been brought to market, relatively little is known about how to design an efficient CO electrolysis device that can achieve high single-pass conversions. For the first time, various cell configurations for CO electrolysis are evaluated and high single-pass conversions exceeding 80% are demonstrated corresponding to gas product streams which are greater than 24 vol% ethylene. Through device engineering liquid product streams that are greater than 1 M in sodium acetate are produced. Finally, an innovative deposition technique is developed to generate thick, highly active catalyst layers for CO reduction cathodes, resulting in improved device performance. The results obtained herein indicate the advantages of CO reduction over direct CO2 reduction. The exploration of various cell configurations informs future efforts to design and build larger scale CO electrolysis devices.

Chapter 1 shows that while nucleophilic substitution reactions are universally taught, they are often much more complicated than we think. A huge amount of work has been done to understand neighboring-group participation in SN1-type reactions both in a qualitative and quantitative sense. Studying the reactivity of dibromides and their surrogates led to important insights in physical organic chem-istry. However, the enantiospecificity and potential synthetic use of such processes are underexplored. Chapter 2 is a reprint of a review I coauthored entitled "Chiral Alkyl Halides: Un-derexplored Motifs in Medicine". While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and me-dicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biologi-cal systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the role that chiral alkyl halides can play in drug discovery. Through a series of case studies, we demonstrate in this chapter that these motifs can indeed be stable under physiological conditions, and that halogenation can enhance bioactivity through both steric and electronic effects. Chapter 3 demonstrates that dihalides could be used to generate a configurational-ly stable bromonium ion either through Lewis acid activation or by using a strongly ionizing solvent. This bromonium ion can then be trapped by a host of nucleophiles inter- and intramolecularly. Using this strategy, a variety of natural products and natural product relevant motifs were synthesized in our laboratory. Chapter 4 describes the importance of studying archaeal lipids and the ongoing efforts toward their total syntheses. Archaeal lipids are structurally unique, their biosynthesis has several unanswered questions, and their biophysical properties have not been studied on pure compounds. Our work describes a highly convergent strat-egy toward GDGT-0, which exploits the molecule's C2 symmetry. We have shown the feasibility of a key enantioselective hydrogenation step, and alternative strategies have been described that may circumvent certain challenges.

Halide perovskites are an important, emerging family of electronic materials which have generated significant scientific interest due to their long carrier lifetimes, facile deposition procedures, and tolerance of large numbers of crystallographic defects. These properties have enabled the lead halide perovskites to be successfully used in a variety of optoelectronic devices including solar cells, light-emitting diodes, and photodetectors. Due to the toxicity of lead and the instability of the lead halide materials, it would be highly desirable to replace the lead halide perovskites with other materials which also demonstrate defect tolerance and long carrier lifetimes. One time-tested approach for identifying promising alternative materials is to synthesize structural analogs; materials with the same structure but different atomic compositions. This dissertation describes my efforts making one family of structural analogs, the halide double perovskites, and evaluating their optoelectronic properties. These materials also adopt the perovskite structure but divide the 2+ charge on the lead site unevenly over multiple sites allowing for a much wider variety of elements to be incorporated into the perovskite lattice. I report the synthesis of the first bismuth bromide double perovskite, Cs2AgBiBr6, and demonstrate that, due to its similar electronic configuration and structure, it possesses many of the same properties that the lead halide perovskites have including a similarly sized bandgap and long carrier lifetime as well as having higher stability. However, unlike the lead perovskites this bismuth double perovskite possesses an indirect bandgap. I next develop a model that describes the atomistic origins of double perovskite band structures. Using a qualitative Linear Combination of Atomic Orbitals method, I describe how band dispersion and band extrema in double perovskites arise naturally from the translational symmetry of the double perovskite structure and detailed bonding interactions. This treatment accurately predicts the band edge positions of almost every known double perovskite and allows for immediate prediction of the electronic structure of new double perovskites from the orbitals of the constituent elements. While the initial work on double perovskites proved promising, the bandgaps of most double perovskites known to date are too large to be useful for optoelectronic devices, particularly solar cells. I demonstrate that the doping or complete substitution of Tl3+ into Cs2AgBiBr6 reduces the bandgap of the material drastically. The completely substituted material, Cs2AgTlBr6, has the smallest bandgap of any known halide perovskite and is much smaller than is typical for bromide perovskites. I show that this small bandgap arises from the metal-to-metal charge transfer nature of double perovskite band edge transitions which allows significant control over the bandgap size through proper choice of metal pairs. Additionally, I demonstrate that Cs2AgTlBr6 undergoes a slow defect reaction, spontaneously evolving Br2 to the atmosphere and n-type doping itself. This defect reaction is analogous to the oxygen-exchange reaction in oxides and is likely general to all halide perovskites. Finally, I show that the halogen exchange reaction we found in Cs2AgTlBr6 occurs in other double perovskites as well. By carefully monitoring the electronic conductivity of the double perovskite Cs2SnI6 I demonstrate that it also undergoes reversible loss and incorporation of I2 with the atmosphere. The kinetics of this reaction follow a one-dimensional diffusion model which can be used to extract diffusion coefficients for halide vacancies and the standard enthalpy of the halogen exchange reaction. Combining these results with ionic conductivity and Hall measurements I am able to construct a detailed defect chemical model. This model predicts the concentrations of major defect species in Cs2SnI6 from experimentally measured thermodynamic parameters. I also demonstrate that deliberate Ba2+ doping of Cs2SnI6 is able to greatly reduce the extent of the halogen exchange reaction and fix the electronic doping to a specific level.

Chapter 1 introduces anaerobic ammonium oxidizing (anammox) bacteria and the ladderane lipids, unusual membrane lipids consisting of linearly concatenated cyclobutane motifs. The distinctive biological features and global applications of anammox bacteria are covered, with a focus on anammox catabolism and the possible function of ladderane lipids. The isolation and structural determination of ladderane lipids are outlined, as well as previous and concurrent synthetic efforts. Chapter 2 details our extensive synthetic efforts toward the synthesis of ladderane lipids. Key features of our synthesis of a [5]-ladderane include a scalable synthesis of key building block bicyclo[2.2.0]hex-2-ene, copper(I)-mediated dimerization of this building block, and C--H functionalization of the ladderane core. We also present a synthesis of [3]-ladderane utilizing a [2+2] photocycloaddition with a chiral dihalide, stereospecific alkylzinc addition, and unusual bis-hydrazone oxidative decomposition. Our efforts to determine for the first time the absolute stereochemical configuration of ladderane lipids are also detailed. Finally, the synthesis of two natural and one unnatural ladderane phospholipid as well as biophysical interrogation of synthetic ladderane phospholipids is presented. Chapter 3 describes an ongoing synthetic campaign toward the phytotoxic sesquiterpene fomannosin. Our synthesis requires a challenging quaternary carbon-forming epoxide opening reaction, as well as a cascade cyclization-Ramberg--Bäcklund ring contraction sequence. Efforts toward the completion of the natural product are presented.