Verdazyl radicals started receiving attention as substrates for organic synthesis only a few years ago. Since then, the chemistry of verdazyl radicals has advanced at a very fast rate. There are now a number of generations of novel molecular scaffolds derived from verdazyl radicals. Traditionally, verdazyl radicals have been synthesized from mono-substituted alkyl hydrazine and phosgene, which are extremely dangerous to handle. Alkyl hydrazines are restricted from being imported into certain countries, including Canada. A completely new alkyl hydrazine- and phosgene-free synthesis is reported in this thesis. The new synthesis, relative to previously reported syntheses of verdazyl radicals, is safer, more economical and provides the ability to derivatize verdazyl radicals to a larger extent. In addition, enantioselective 1,3-dipolar cycloaddition reactions with various metal- or organo-catalysts are reported. The project is still in progress with the highest e.e. of > 90%.

Verdazyl radicals are a family of multicoloured stable free radicals. Aside from the defining backbone of four nitrogen atoms, these radicals contain multiple highly modifiable sites that grant them a high degree of derivatization. Despite having been discovered more than half a century ago, limited applications have been found for the verdazyl radicals and little is known about their chemistry. This thesis begins with an investigation to determine whether verdazyl radicals have a future as mediating agents in living radical polymerizations and progresses to their application as substrates for organic synthesis, an application that to date has not been pursued either with verdazyl or nitroxide stable radicals. The first part of this thesis describes the successful use of the 1,5-dimethyl-3-phenyl-6-oxoverdazyl radical as a mediating agent for styrene and n-butyl acrylate stable free radical polymerizations. The study of other verdazyl derivatives demonstrated the impact of steric and electronic properties of the verdazyl radicals on their ability to mediate polymerizations. The second part of this thesis outlines the initial discovery and the mechanistic elucidation of the transformation of the 1,5-dimethyl-3-phenyl-6-oxoverdazyl radical into an azomethine imine, which in the presence of dipolarophiles, undergoes a [3+2] 1,3-dipolar cycloaddition reaction to yield unique pyrazolotetrazinone structures. The reactivity of the azomethine imine and the scope of the reaction were also examined. The third part of this thesis describes the discovery and mechanistic determination of a base-induced rearrangement reaction that transforms the verdazyl-derived pyrazolotetrazinone cycloadducts into corresponding pyrazolotriazinones or triazole structures. The nucleophilicity, or the lack thereof, of the base employed leading to various rearrangement products was examined in detail. The final part of this thesis demonstrates the compatibility of the verdazyl-initiated cycloaddition and rearrangement reactions with the philosophy of diversity-oriented synthesis in generating libraries of heterocycles. A library of verdazyl-derived heterocycles was generated in a short amount of time and was tested non-specifically for biological activity against acute myeloid leukemia and multiple myeloma cell lines. One particular compound showed cell-killing activity at the 250 mM range, indicating future potential for this chemistry in the field of drug discovery.

The emergence of verdazyl radicals as starting materials for organic synthesis is providing a unique opportunity to create a variety of distinctive heterocyclic scaffolds. These stable radicals have previously been used as spin probes, polymerization inhibitors, mediators of living radical polymerizations, and as substrates for molecular-based magnets. However, verdazyl radicals have never been employed to fulfill an organic synthetic role until recently. In an effort to pioneer the chemistry behind verdazyl radicals as novel organic substrates, our lab has been inspired to expand and explore the scope of reactions involving their synthetic utility. This thesis assesses the synthetic versatility of verdazyl radicals by constructing a library of structurally complex and diverse verdazyl-derived heterocycles in an approach called diversity-oriented synthesis. The synthetic versatility was further expanded to the preparation of a biphenyl-stacked biphenylophane, which exhibited interesting structural and conformational features as highlighted herein.

Verdazyl radicals are a family of multicoloured stable free radicals. Aside from the defining backbone of four nitrogen atoms, these radicals contain multiple highly modifiable sites that grant them a high degree of derivatization. Despite having been discovered more than half a century ago, limited applications have been found for the verdazyl radicals and little is known about their chemistry. This thesis begins with an investigation to determine whether verdazyl radicals have a future as mediating agents in living radical polymerizations and progresses to their application as substrates for organic synthesis, an application that to date has not been pursued either with verdazyl or nitroxide stable radicals. The first part of this thesis describes the successful use of the 1,5-dimethyl-3-phenyl-6-oxoverdazyl radical as a mediating agent for styrene and n-butyl acrylate stable free radical polymerizations. The study of other verdazyl derivatives demonstrated the impact of steric and electronic properties of the verdazyl radicals on their ability to mediate polymerizations. The second part of this thesis outlines the initial discovery and the mechanistic elucidation of the transformation of the 1,5-dimethyl-3-phenyl-6-oxoverdazyl radical into an azomethine imine, which in the presence of dipolarophiles, undergoes a [3+2] 1,3-dipolar cycloaddition reaction to yield unique pyrazolotetrazinone structures. The reactivity of the azomethine imine and the scope of the reaction were also examined. The third part of this thesis describes the discovery and mechanistic determination of a base-induced rearrangement reaction that transforms the verdazyl-derived pyrazolotetrazinone cycloadducts into corresponding pyrazolotriazinones or triazole structures. The nucleophilicity, or the lack thereof, of the base employed leading to various rearrangement products was examined in detail. The final part of this thesis demonstrates the compatibility of the verdazyl-initiated cycloaddition and rearrangement reactions with the philosophy of diversity-oriented synthesis in generating libraries of heterocycles. A library of verdazyl-derived heterocycles was generated in a short amount of time and was tested non-specifically for biological activity against acute myeloid leukemia and multiple myeloma cell lines. One particular compound showed cell-killing activity at the 250 mM range, indicating future potential for this chemistry in the field of drug discovery.

The emergence of verdazyl radicals as starting materials for organic synthesis is providing a unique opportunity to create a variety of distinctive heterocyclic scaffolds. These stable radicals have previously been used as spin probes, polymerization inhibitors, mediators of living radical polymerizations, and as substrates for molecular-based magnets. However, verdazyl radicals have never been employed to fulfill an organic synthetic role until recently. In an effort to pioneer the chemistry behind verdazyl radicals as novel organic substrates, our lab has been inspired to expand and explore the scope of reactions involving their synthetic utility. This thesis assesses the synthetic versatility of verdazyl radicals by constructing a library of structurally complex and diverse verdazyl-derived heterocycles in an approach called diversity-oriented synthesis. The synthetic versatility was further expanded to the preparation of a biphenyl-stacked biphenylophane, which exhibited interesting structural and conformational features as highlighted herein.

Significant advances in the design, synthesis, and chemistry of verdazyl radicals have been made, including (i) the systematic study of the electrochemistry of verdazyl radicals, (ii) the development of formazans as ancillary ligands en route to inorganic verdazyl radicals, and (iii) magnetostructural studies of verdazyl diradicals and copper (II) verdazyl complexes. The electrochemical properties of a family of verdazyl radicals were explored. Type I and type II verdazyl radicals were reversibly oxidized and reduced, and the potentials of such processes observed to be sensitive to substituent effects. The incorporation of electron-withdrawing substituents made verdazyl radicals harder to oxidize and easier to reduce, while the presence of electron-donating groups had the opposite effect. Type II verdazyls were harder to oxidize and less delocalized (based on relative cell potentials) than type I analogues. The difficulty in oxidation of type II verdazyls relates to the electron-withdrawing nature of the carbonyl functionality, while the decreased delocalization relates to twisting of the N-substituents. Twisting of the N-substituents was confirmed through the use of X-ray crystal structures, and DFT calculations were used to illustrate the decrease in delocalization of the unpaired electron associated with the twisting. The similarities of formazans to -diketiminate ligands prompted the study of their coordination chemistry. Boratatetrazines, the first main group complexes of formazans illustrated their ability to mimick beta-diketiminate ligands. Reduction of boratatetrazines with cobaltocene afforded highly reactive borataverdazyl radical anions isolobal to parent organic systems. The radicals were readily oxidized back to the boratatetrazine precursors limiting their characterization to the solid-state. Synthetic pathways to 3-substituted formazans allowed for the incorporation of bulky N-substituents, a feature of -diketiminates that has influenced their utility as catalysts. 3-Cyanoformazans were shown to exist as either the open or closed structure in solution and the solid-state, while 3-nitroformazans exist exclusively as the closed strcutre due to the presence of the relatively large nitro-substituent. A number of transition metal complexes of 3-substituted formazans were synthesized, and their X-ray crystal structures used to establish a correlation between steric bulk at the ligand and complex structure. When ortho-substituents are incorporated the N-aryl substituents twist relative to the formazan backbone, while relatively smaller N-aryl substituents remain relatively planar. Palladium hexafluoroacetylacetonate complexes of formazans were anticipated to have utility as precursors to palladaverdazyls due to their electron poor nature. However, although the complexes did allow for the structure property relationship of metal-formazan complexes to be further developed, palladaverdazyls were not realized. Comparison with boratatetrazines suggests the nature of the Pd-N bond may play a role in the instability of palladaverdazyls. The synthesis and characterization of verdazyl-based spin dimers was reported. The incorporation of iso-propyl N-substituents allowed for the first truly stable verdazyl diradicals to be isolated. Electrochemical, electronic, and magnetic properties of diradicals bridged by para- and meta-benzene were explored. Diradicals bridged by para-benzene were antiferromagnetically coupled while meta-benzene bridged diradicals were ferromagnetically coupled. Magnetostructural studies of copper (II) complexes of verdazyls were complicated by the coordinative flexibility of copper (II) ions and the presence of Jahn-Tellar distorted ligand fields. However, a correlation between structure and properties was established: axially bound verdazyl radicals were weakly ferromagnetically coupled to copper (II) ions, and equatorially bound verdazyl radicals were strongly antiferromagnetically coupled to copper (II).