Discovery of new catalytic reactions through mechanistically guided screening

研究性质***纽曼集团的研究重点是将现代技术应用于基础化学和应用化学的进步。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。本提案的重点是应用HTE来发现容易获得的构建块的均相催化反应。作为一个年轻的研究小组，我们的目标是承担高影响力的项目，建立一个独特的，世界级的研究项目。这将通过三个阶段进行：1)反应发现、优化和机制阐明；2)用于药物和生物质衍生原料药的合成；3)利用我们对催化的进一步了解来进一步发展反应。本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，原子经济的烯烃-醛偶联反应，以及用于合成重氮物种的n20 -炔“点击”反应。***对加拿大人的意义、预期结果和利益***合成化学在社会最重要的需求中发挥着重要作用。我们的健康依赖于救生药物的开发，其中大多数是小有机分子。新的合成方法使药物化学家能够生产更大、更多样化的文库，增加了发现下一个拯救生命的疗法的机会。可持续性是另一个关键焦点——减少人类对环境的影响和减少对不可再生化学品的依赖是很重要的。需要以无害环境的方式利用丰富资源的新化学品。拟议的研究工作通过关注简单分子的催化，低浪费偶联来制备可能用于制药和大宗化学合成的复杂结构，从而满足这些需求。在这些研究中获得的知识也可以对加拿大的大型石油、散装化工和生物质工业产生直接影响，这些工业正面临着日益激烈的竞争和减少污染的需求。我们集团寻求直接的、可持续的方法，从现成的原料中创造增值化学品，从而带来新技术，以加强化学工业。最重要的是，该项目为培养有机合成、催化和绿色化学领域的前瞻性科学家提供了丰富的环境；这些领域将对我们社会未来几代人的福祉发挥关键作用。我们特别注重对化学反应的基本理解，并结合使用新技术来简化发现过程，这是一种独特的方法，将培养学生在工业和学术界竞争性工作所需的技能

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.**