Development and application of decarboxylative and desulfinative cross-coupling reactions

拟议研究计划的目标：开发新的合成方法和构建复杂的天然产物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旧问题，并以一种使转化更高效、更高产量、尽可能对环境友好的方式来解决新问题。我的研究项目主要集中在钯催化的(杂环)芳烃的脱羧基和脱硫基的交叉偶联反应，以形成碳-碳键，这是合成有机化学和药物化学中的一个重要转变。该反应避免了对具有金属物种的偶联伙伴进行预官能化的需要。反应的主要副产物二氧化碳或二氧化硫是反应的驱动力，不会产生需要净化步骤才能去除的金属杂质。我的研究将集中在合成材料和医药用的噻吩基杂芳烃；利用这些方法在环境友好的条件下从简单和/或未得到充分利用的起始原料合成增值化学品，并对转化的作用机理有一个清晰的了解，以提高工业研究用途的实用性。此外，还将研究流动化学在这些交叉耦合中的应用。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。一个关键的目标将是以机理研究为指导，回收产生的二氧化硫和二氧化碳，以便将这些转化用作捕获和释放战略，以提高这些反应的环境友好性潜力。在钯催化的交叉偶联反应中使用能挤出SO2和/或CO2等气体的亲核剂是一个相对较新的发现。捕获和回收产生的二氧化硫和二氧化碳的能力将显著增加这些转化的效用。生物原材料的应用将增加这些现成原材料的增值潜力。因此，这项研究计划的新颖性在于采用这些新方法，以最环保的方式从简单易得的起始材料合成实用材料。最后，我的研究的主要“产品”是培训有效的研究人员和批判性思想家，这将在他们毕业后在不同领域做出贡献时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.**