Development and application of decarboxylative and desulfinative cross-coupling reactions

脱羧、脱亚磺交叉偶联反应的开发及应用

• 批准号: RGPIN-2015-04749
• 负责人: Forgione, Pat
• 金额: $ 3.28万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=650942
• 关键词: Development; application; decarboxylative; desulfinative; cross

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.**

拟议的研究计划的目标：新合成方法的开发和复杂的天然产品的构建位于合成有机化学的核心。更大的全球意识的出现使化学家促使化学家重新审视旧问题，并以一种使转型更有效，更高的收益和环境良性的方式解决新问题。我的研究计划的重点是钯介导的（异源）芳香族剂的脱羧和去硫化的交叉偶联反应，以形成碳 - 碳键，这在合成有机化和药物化学中都是至关重要的转化。该反应规定了对耦合伴侣与金属物种的耦合伴侣的必要性。反应，二氧化碳或二氧化硫的主要副产品是反应的驱动力，并且不产生基于金属的杂质，需要纯化步骤以进行除去。我的研究将重点介绍硫烯衍生的杂芳烃用于材料和药用应用中的合成；通过在环保条件下简单和/或未充分利用的起始材料中采用这些方法的增值化学物质的合成，并清楚地了解转化的手术机制，以改善工业研究使用的实用性。此外，将检查流化学对这些交叉耦合的应用。流化学可能在确保这些转换的实用性中起关键作用，以使它们对化学工业更有用。一个关键目的是将机械研究作为回收生成的SO2和CO2的指南，以利用这些转换作为捕获和释放策略，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挤出气体（例如SO2和/或CO2）的亲核试剂的使用是相对较新的发现。捕获和回收SO2和CO2生成的能力将显着增加这些转换的效用。对基于生物的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，该研究计划的新颖性在于采用这些新方法来合成以最环境友好的方式从简单且容易获得的起始材料中有用的材料。最后，我的研究的主要“产品”是对有效的研究人员和关键思想家的培训，这些培训将为加拿大社会在毕业后的各种领域的贡献中增加价值。**