Development and application of decarboxylative and desulfinative cross-coupling reactions

拟议研究计划的目标：新合成方法的开发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重新审视旧问题，并以一种使转化更有效，更高产和尽可能环境友好的方式解决新问题。我的研究项目主要集中在钯介导的脱羧和反式交叉偶联反应（杂）芳烃形成碳-碳键，这是一个重要的转变，在合成有机化学和药物化学。该反应避免了用金属物质预官能化偶联配偶体的需要。反应的主要副产物二氧化碳或二氧化硫充当反应的驱动力，并且不产生需要纯化步骤来去除的金属基杂质。我的研究将集中在合成噻吩衍生的杂芳族化合物用于材料和医药应用;使用这些方法从简单和/或未充分利用的起始原料在环境友好的条件下合成增值化学品，并清楚地了解转化的操作机制，以提高工业研究用途的实用性。此外，流动化学的应用，这些交叉耦合将被检查。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。一个关键目标是利用机理研究作为指导，回收产生的SO2和CO2，以便将这些转化用作捕获和释放策略，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气体如SO2和/或CO2是一个相对较新的发现。捕获和回收产生的SO2和CO2的能力将大大增加这些转化的效用。生物基原材料的应用将增加这些容易获得的起始材料的增值潜力。因此，该研究计划的新奇在于采用这些新方法以最环保的方式从简单且易于获得的起始材料合成实际有用的材料。最后，我的研究的主要“产品”是有效的研究人员和批判性思想家，将在毕业后在不同领域的后续贡献加拿大社会增值的培训。

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.