Development of Metal Complexes for Use in Non-Aqueous Redox Flow Batteries and C-H Functionalization of N-Heterocycles

Abstract

Batteries represent a sustainable energy storage technology for the integration of renewable resources into the electrical grid. The first part of my research focused on the development of metal complexes as redox active materials for non-aqueous redox flow batteries. Flow batteries are rechargeable batteries based on solvated electroactive species that are flowed between storage tanks and electrochemical conversion cells to store or release electrical energy. Chapter 2 describes a systematic study on the impact of the bipyridine ligand structure on the solubility and electrochemistry of [Cr(bpy)3] complexes that afford six reversible redox couples over ∼2 V and solubilities approaching 1 M. These studies reveal that solubility is highly dependent on the oxidation state of the metal complex with solubility differences up to 4 orders of magnitude between the Cr(0) and the Cr(III) complexes. In contrast, modifications to the metal complex have minimal impact on the electrochemical properties. Furthermore, this investigation led to the identification of a promising Cr complex that was evaluated in charge/discharge experiments affording a two-electron transfer at each of the electrodes with efficiencies of 70%. The second part of my research is focused on the development of C–H functionalization methodologies. The conversion of carbon–hydrogen (C–H) bonds into new functional groups represents a powerful strategy for the synthesis of organic molecules. The advent of C–H functionalization has enabled medicinal chemists to utilize a late-stage functionalization approach to efficiently convert the C–H bonds in drug candidates to new chemical entities. Despite tremendous progress in the field, selective C–H functionalization of N-heterocycles remains challenging. Chapter 3 describes a room-temperature photoredox-catalyzed method for the C–H amination of hetero(arenes). This chapter describes the design and development of N-trifluoroacyloxyphthalimide as precursor to nitrogen-centered radical intermediates. N-trifluoroacyloxyphthalimide is proposed to undergo a single electron reduction by the photocatalyst leading to an imidyl radical. The C–H amination protocol addresses several limitations from previous methods such as the need for expensive oxidants and elevated temperatures. The mild reaction conditions enabled the preparation of several N-heterocyclic amine products, which are common motifs in bioactive molecules. Furthermore, the synthesis of N-trifluoroacyloxysaccharine afforded highly electrophilic N-radicals, thereby permitting further reaction optimization to lower the photocatalyst and hetero(arene) loading. Chapter 4 describes the development of a Pd-catalyzed transannular C–H arylation of alicyclic amines. A key design principle is the use of the nitrogen atom in these substrates to direct the Pd-catalyst to remote C–H bonds in the ring. This approach leverages the high-energy boat conformer species to achieve transannular C–H activation and subsequent C–C bond formation. The reaction exhibits high compatibility with a wide range of hetero(aryl) iodides in the diversification of 3-azabicyclo[3.1.0]hexane. Several alicyclic amines undergo C–H arylation in modest to good yields. The methodology was employed for the late-stage functionalization of bioactive molecules including amitifadine, varenicline and cytisine. Furthermore, several directing groups were synthesized which showed a wide range of reactivity toward the C4–H arylation of piperidine. Chapter 5 describes the identification of pyridinecarboxylic acid ligands for the Pd-catalyzed C–H functionalization of azabicycloalkanes. The ligand additives were found to dramatically improve the reactivity. Kinetic studies reveal that the role of the ligand is to rescue deactivated Pd species. Reaction optimization enables the challenging distal C–H functionalization of diverse alkaloids such as tropane.