Development and application of decarboxylative and desulfinative cross-coupling reactions

新合成方法的发展和复杂天然产物的构建是合成有机化学的核心。更大的全球意识的出现促使化学家们重新审视老问题，并以一种使转化更有效、产量更高、尽可能环保的方式解决新问题。我的研究重点是钯介导的（杂）芳烃脱羧和脱硫交叉偶联反应，以形成碳-碳键，这是合成有机化学和药物化学的重要转变。这种反应避免了偶联物与金属物质的预官能化。该反应的主要副产物二氧化碳或二氧化硫作为反应的驱动力，不会产生需要净化步骤才能去除的金属基杂质。我的研究将集中在合成噻吩衍生的杂芳烃，用于材料和医药应用；在环境友好的条件下，利用这些方法从简单和/或未充分利用的原料合成增值化学品，并明确了解转化的运作机制，以提高工业研究使用的实用性。此外，流动化学在这些交叉耦合中的应用将被检查。流动化学可能在确保这些转化的实用性方面发挥关键作用，以便使它们对化学工业更有用。一个关键目标将是利用机理研究作为指导，以回收所产生的二氧化硫和二氧化碳，以便将这些转化作为一种捕获和释放战略，以提高这些反应的环境友好潜力。在钯催化的交叉偶联反应中使用亲核试剂挤出SO2和/或CO2等气体是一个相对较新的发现。捕获和回收所产生的SO2和CO2的能力将大大增加这些转换的效用。生物基原料的应用将增加这些现成原料的增值潜力。因此，这项研究计划的新颖之处在于采用这些新方法，以最环保的方式，从简单易得的原料合成实际有用的材料。最后，我的研究的主要“产品”是培养有效的研究人员和批判性思考者，他们将在毕业后在各个领域做出贡献，为加拿大社会增加价值

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.**