Discovery of new catalytic reactions through mechanistically guided screening

研究性质*纽曼小组的研究侧重于应用现代技术促进基础和应用化学的发展。特别是，我们正在探索使用高通量实验(HTE)和流动化学平台来合成有价值的分子。这项建议的重点是应用热膨胀技术来发现容易获得的构件的均相催化反应。作为一个年轻的研究团队，我们的目标是承担具有高影响力的项目，目的是建立一个独特的、世界级的研究计划。这将通过三个阶段进行：1)反应发现、优化和机理阐明；2)应用于药物和生物质衍生的大宗化学品的合成；3)利用我们对催化的日益增长的理解来进一步反应发展。这项研究计划描述了第一阶段的5年计划，发现新的化学反应，包括新的C-C交叉偶联反应，原子经济的烯醛偶联反应，以及用于合成重氮物种的N2O-炔烃‘点击’反应。*意义，预期结果，对加拿大人的好处*合成化学在最重要的社会需求中发挥着巨大的作用。我们的健康依赖于救命药物的开发，其中大部分是有机小分子。新的合成方法使药物化学家能够产生更大、更多样化的文库，增加了找到下一种拯救生命的疗法的机会。可持续性是另一个关键重点--重要的是减少人类对环境的影响，减少对不可再生化学品的依赖。需要以环境友好的方式利用丰富的资源的新的化学方法。这项拟议的研究致力于满足这些需求，将重点放在简单分子的催化、低废物耦合上，以制备复杂结构，这些结构可能会在制药和大宗化学合成中使用。从这些研究中获得的知识也可能对加拿大大型石油、散装化学品和生物质行业产生直接影响，这些行业正面临着日益激烈的竞争和减少污染的需求。我们的团队寻求直接、可持续的方法，从现成的原料中创造增值化学品，从而带来加强化学工业的新技术。最重要的是，该计划为培训具有前瞻性思维的有机合成、催化和绿色化学科学家提供了一个丰富的环境，这些领域将在我们的社会福祉中发挥关键作用，世世代代。我们特别注重对化学反应的基本了解，并结合使用新技术来简化发现过程，这是一种独特的方法，将培训学生在工业和学术界具有竞争力的工作所需的技能。**

Nature of the research***Research in the Newman group focuses on the application of modern technologies to the advancement of fundamental and applied chemistry. In particular, we are exploring the use of high throughput experimentation (HTE) and flow chemistry platforms for the synthesis of valuable molecules. This proposal focuses on the application of HTE to the discovery of homogeneously catalyzed reactions of readily available building blocks. Being a young research group, our goal is to take on high impact projects with the intention of establishing a unique, world-class research program. This will occur through three phases: 1) Reaction discovery, optimization, and mechanism elucidation; 2) Application to the synthesis of pharmaceuticals and biomass-derived bulk chemicals; and 3) Use of our increased understanding of catalysis for further reaction development. This research proposal describes a 5 year plan for phase 1, discovery of new chemical reactions, including a new C-C cross-coupling reaction, an atom economical olefin-aldehyde coupling, and an N2O-alkyne `click' reaction for the synthesis of diazo species.***Significance, expected outcomes, and benefits to Canadians***Synthetic chemistry has a great role to play in the most important needs for society. Our health relies on the development of lifesaving pharmaceuticals, the majority of which are small organic molecules. New synthetic methods allow medicinal chemists to produce larger, more diverse libraries, increasing the chances of finding the next life-saving therapeutics. Sustainability is another critical focus - it is important to decrease human impact on the environment and reduce dependency on non-renewable chemicals. New chemistries are needed that make use of abundant resources in an environmentally benign manner. The proposed research works towards these needs by focusing on catalytic, low-waste coupling of simple molecules to prepare complex structures that may find use in pharmaceutical and bulk chemical synthesis. The knowledge gained in these studies can also have a direct impact on Canada's large oil, bulk chemical, and biomass industries, who are facing increasing competition and demand for decreased pollution. Our group seeks direct, sustainable methods for creating value-added chemicals from readily available feedstocks, leading to new technologies to strengthen the chemical industry. Most importantly, the program provides an enriching environment for training forward-thinking scientists in organic synthesis, catalysis, and green chemistry; areas that will play a key role in the well-being of our society for many generations. Our particular focus on fundamental understanding of chemical reactions combined with the use of new technologies to streamline the discovery processes is a unique approach that will train students in the skills necessary for competitive jobs in industry and academia.**