SusChEM: Copper Catalyzed C-H Functionalization

NSF 化学催化计划支持乔治城大学 Timothy H. Warren 教授设计和开发碳-氮 (C-N)、碳-氧 (C-O) 和碳-碳 (C-C) 键形成新方案的努力。这项研究是通过对关键碳氢 (C-H) 活化和 C 官能团 (C-FG) 键形成反应的详细了解来推动的，以激发新的催化剂结构以实现可调节的选择性。该团队开发了与未活化胺的C-H胺化反应、与醇和受保护酚的C-H醚化反应、与硝基烷烃的C-H硝基烷基化反应、与酮的C-H烷基化反应以及通过其他H-FG底物的C-FG形成反应。他们从合成和机械角度研究了关键的铜 (II)-FG 中间体，以了解它们在 C-FG 键形成和 H 原子抽象反应中的作用。 这些化学家研究了新的配体变化，以提高特别活泼的铜 (II)-FG 中间体的寿命，并指导 C-FG 键形成步骤。一系列具有合成价值、机械相关的 C-H 官能化反应解决了可持续化学合成中的重要挑战，例如使用氨将碳氢化合物转化为胺。这项研究属于“SusChEM”计划，因为它提倡使用非贵金属催化剂——铜——而不是更稀有和昂贵的替代品。 与默克的合作使乔治城大学的学生能够访问位于新泽西州拉威的默克催化和自动化实验室。 在默克实验室，学生们采用高通量方法来发现新的 C-H 官能化催化剂和催化转化。与 Karsten Meyer 教授（德国埃尔兰根大学）和 Tom Cundari 教授（北德克萨斯州大学）的持续合作分别实现了深入的光谱研究和计算见解。通过“更高成就”组织，沃伦教授与来自资源贫乏社区低收入家庭的高风险中学生建立联系，每年夏天在乔治城举行的化学展（90-100 名学生）中为他们的中学生提供有趣的科学编程，并在每个学年华盛顿特区公立学校关闭时至少对乔治城进行一次小型访问（10-20 名学生）。 NSF 化学催化计划支持乔治城大学蒂莫西·H·沃伦教授在设计和研究方面所做的努力。开发碳-氮（C-N）、碳-氧（C-O）和碳-碳（C-C）键形成的新方案。 这项工作涉及有价值且可持续的化学合成，例如使用氨将碳氢化合物转化为胺。开发与碳形成键的新方法，消除对特定底物和保护/脱保护步骤的需求，可以加速有机化学合成并提高工业产量，同时减少环境足迹并增强化学合成的可持续性。虽然许多C-H官能化系统使用钯和其他贵金属，但这种方法使用铜——一种地球上储量丰富、成本低、毒性小的金属。 工业合作使研究生能够探索高通量的发现方法，同时提高自己的就业市场能力。 美国和德国正在进行的合作也为学生提供了在全球社区进行研究的更广阔的视角，提高了他们的技术和团队合作技能。 沃伦教授和他的团队与来自资源贫乏社区低收入家庭的高风险中学生建立联系，每年夏天通过化学展以及哥伦比亚特区公立学校停课时偶尔举办的乔治城大学小型访问提供科学节目。

The NSF Chemical Catalysis Program supports the efforts of Professor Timothy H. Warren of Georgetown University in the design and development of new protocols for carbon-nitrogen (C-N), carbon-oxygen (C-O), and carbon-carbon (C-C) bond formation. This research is propelled by a detailed understanding of the key carbon-hydrogen (C-H) activation and C-functional group (C-FG) bond forming reactions to motivate new catalyst architectures for tunable selectivity. The team develops C-H amination reactions with unactivated amines, C-H etherification with alcohols and protected phenols, C-H nitroalkylation with nitroalkanes, and C-H alkylation with ketones as well as C-FG forming reactions via other H-FG substrates. They synthetically and mechanistically examine key copper(II)-FG intermediates to understand their roles in C-FG bond formation and H-atom abstraction reactions. These chemists examine new ligand variations to enhance the lifetime of particularly reactive copper(II)-FG intermediates as well as to direct the C-FG bond forming step. A wide range of synthetically valuable, mechanistically related C-H functionalization reactions address important challenges in sustainable chemical synthesis, such as the conversion of hydrocarbons to amines using ammonia. This research falls under the "SusChEM" initiative as it promotes the use of non-precious metal catalysts - copper - over more rare and expensive alternatives. Collaboration with Merck allows Georgetown students to access the Merck Catalysis and Automation Laboratory in Rahway, NJ. At the Merck laboratories, the students employ high throughput approaches to the discovery of new C-H functionalization catalysts and catalytic transformations. Ongoing collaborations with Prof. Karsten Meyer (U. Erlangen, Germany) and with Prof. Tom Cundari (U. North Texas) enable in depth spectroscopic studies and computational insights, respectively. Through the organization "Higher Achievement", Professor Warren connects with high-risk middle school students from low income families in under-resourced communities, providing fun science programming to their middle school scholars in a Chemistry Show (90-100 students) held at Georgetown each summer as well as at least one smaller visit (10-20 students) to Georgetown during each academic year when DC public schools are closed.The NSF Chemical Catalysis Program supports the efforts of Professor Timothy H. Warren of Georgetown University in the design and development of new protocols for carbon-nitrogen (C-N), carbon-oxygen (C-O), and carbon-carbon (C-C) bond formation. This work addresses valuable and sustainable chemical synthesis, such as the conversion of hydrocarbons to amines using ammonia. The development of new methodologies for bond formation with carbon that eliminate the need for specific substrates and protection / deprotection steps can accelerate organic chemical synthesis as well as enhance industrial throughput - all while reducing the environmental footprint and enhancing the sustainability of chemical synthesis. While many C-H functionalization systems employ palladium and other noble metals, this approach employs copper - an Earth-abundant metal of low cost and toxicity. Industrial collaborations allow graduate students to explore high throughput approaches to discovery while increasing their own job marketability. Ongoing collaborations within the U.S. and in Germany also provide students with the broader perspective of performing research in a global community, enhancing both their technical and teamwork skills. Professor Warren and his group connect with high-risk middle school students from low income families in under-resourced communities, providing science programming via a Chemistry Show each summer as well as during occasional smaller visits to Georgetown Univeristy held when District of Columbia public schools are closed.