Development and application of decarboxylative and desulfinative cross-coupling reactions

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Objectives of the Proposed Research Program: The development of new synthetic methods and the construction of complex natural products lie at the heart of synthetic organic chemistry. The emergence of a greater global consciousness has pushed chemists to revisit old problems and tackle new ones in a manner that makes transformations more efficient, higher yielding and as environmentally benign as possible. My research program focuses on palladium-mediated decarboxylative and desulfinative cross-coupling reactions of (hetero-)aromatics for the formation of carbon-carbon bonds, which is a vital transformation in both synthetic organic and medicinal chemistry. This reaction circumvents the need for the pre-functionalization of the coupling partner with a metal species. The main by-product of the reaction, carbon dioxide or sulfur dioxide, acts as a driving force for the reaction and does not generate metal-based impurities that require a purification step for their removal. My research will focus on the synthesis of thiophene-derived heteroaromatics for use in materials and medicinal applications; synthesis of value-added chemicals employing these methods from simple and/or underutilized starting materials in environmentally friendly conditions, and gaining a clear understanding of the operative mechanism of the transformation in order to improve the practicality for industrial research use. Additionally, the application of flow-chemistry to these cross-coupling will be examined. Flow-chemistry may play a key role in ensuring the practicality of these transformations in order to render them more useful to the chemical industry. A key aim will be to use the mechanistic studies as a guide to recycle the SO2 and CO2 generated in order to employ these transformations as a capture and release strategy to improve the environmental-friendliness potential of these reactions. The use of nucleophiles that extrude gases such as SO2 and/or CO2 in palladium-catalyzed cross-coupling reactions is a relatively recent finding. The ability to capture and recycle the SO2 and CO2 generated will significantly add to the utility of these transformations. Applications to bio-based raw materials will increase the value-added potential of these readily available starting materials. As such, the novelty of this research program lies in employing these new methods to synthesize materials that are practically useful from simple and readily available starting material in the most environmentally friendly possible way. Finally, the principal "product" of my research is the training of effective researchers and critical thinkers that will add value to Canadian society in their subsequent contributions in a diverse range of fields following graduation.**