Search

This thesis is concerned with the synthesis and reactions of functionalised 3- liydroxypyridines, in particular 2-aryl- and 2-heteroary 1-3-liydroxypyridines by non- coupling methodology, from furan precursors. Chapter 1 reviews the synthesis and reactions of 3-hydroxypyridines. Chapter 2 describes the synthesis of 2-acylfurans via differing methods, which include acylation of the furan nucleus, Grignard reactions of furaldehydes and, most notably, reaction of lithiofurans with reagents containing a nitrile component. Chapter 3 concerns reaction of acylfurans with ammonia at high pressure and temperature to produce 3-hydroxypyridines. We have found that this ring expansion is able to withstand many differing substituents including bromine. Further development of the pyridine ring system involves reaction of the ring atoms or substituents, including protection of the hydroxy group. This ring expansion was used in the development of a novel azabenzotriazole starting from a simple furan compound, and this is reported in Chapter 4.The methodology described in this thesis is versatile and has allowed access to a range of novel pyridine derivatives in synthetically useful quantities which should be of interest in many areas of organic chemistry.

Towards the end goal of high rate tensile characterization of any material, existing ideas and newly developed technology have been combined in the form of a test platform dubbed the FIRE system. The acronym stands for Fully Instrumented Ring Expansion, a concept that is capable of evaluating the dynamic behavior of a wide range of materials in tension at strain rates well in excess of 1000/s. At the center of the design is a collection of techniques used to impulsively drive ring shaped samples radially outward in a highly symmetric fashion. This geometry avoids many of the traditional pitfalls associated with high rate testing such as end effects and critical extension speeds. Precision velocimetry has been adapted to the system utilizing state of the art optical and electronic equipment via a subassembly known as PDV (Photon Doppler Velocimetry). The PDV capabilities at present include determination of sample velocities up to 3.2 km/s with simultaneous displacement resolution on the order of 1-10 microns. As validation of the techniques developed, numerous representative material studies were carried out and compared to established data from other sources. Results were found to be in favorable agreement, verifying the efficacy of the methods. Additionally, the expanding ring test has been applied in conjunction with sample types and actuator technologies not reported previously. This provides an expanded usefulness to the test, which has been developed to the point now of being user friendly.

The development of new synthetic methods advances the study of chemistry on many fronts, including new drugs for the treatment of human disease and new materials. The copper-catalyzed rearrangement of vinyl heterocycles is one such method, providing access to a wide array of five-membered oxygen, nitrogen, and sulfur-containing heterocycles. To harness the true potential of a new methodology, an understanding of the mechanistic underpinnings is required. Utilizing an array of mechanistic tools, the rearrangement of vinyl aziridines is studied in detail. Using mechanistically inspired metal additives, a dramatic acceleration of the rearrangement of vinyl aziridines was realized. Demonstrating the use of in situ reducing agents significantly accelerate the rearrangement, suggesting a copper(I) species is the active catalytic species. This was corroborated through the use of (COD)Cu(hfacac) as a copper(I) starting point. Detailed NMR kinetic studies revealed the relative importance of olefin and sulfonamide electronics, and that the rearrangement is first order in substrate and first order in catalyst. As a result, a new catalytic system was discovered, which provides enhanced chemoselectivity and milder reaction conditions towards five-membered heterocycles. In addition, studying the mechanism provided a new direction for future rational catalyst       designs towards more active catalysts, and catalysts for chiral applications, such as asymmetric desymmetrization. To further demonstrate the utility of the new copper(I) catalytic system, an expedient and scalable approach was designed utilizing (COD)Cu(hfacac) in the first total synthesis of members of a family of heterocyclic labdane natural products. Through synthesis, conformation and clarification of the structural assignment of isolated smallmolecules was realized. The route provided access to quantities of material for biological screening purposes, and the versatility of the route could be used to provide synthetic analogues of the natural structures.