Strong C-H Bond Activation through Superbase Incorporation and pKa Matching

在化学系化学合成项目的支持下，宾夕法尼亚大学的Neil C. Tomson将研究碳氢键的选择性裂解，这是化学领域的一个重大挑战。从化石燃料到塑料和其他材料，这些臭名昭著的不活泼的键广泛存在。以受控方式分裂C-H键的方法的发展有望帮助我们对其反应化学的基本理解，并为生物系统如何相对容易地进行这些反应提供见解。预计这些方法还将促进技术发展，包括使用丰富的原料化学品，如甲烷，用于替代燃料生产。这个项目的受训者将熟练地进行对空气和湿度高度敏感的合成化学。这项工作将通过使用现代计算化学技术来补充，这将为在实验室中进行的合成化学提供信息丰富的补充。该项目将有助于正在进行的旨在向高中生介绍能源科学主题的推广工作。这项工作将包括制作短视频，以一种易于理解和吸引人的方式为解释化学的重要方面提供视觉辅助。这些视频将突出高中课程中涵盖的概念，并与本研究项目的替代燃料重点相吻合。由于几个原因，激活脂肪族C-H键是具有挑战性的，包括需要强大的热力学驱动力来裂解C-H键。众所周知，铜离子与O2结合可以介导酶中强烈的C-H键激活反应，但均相系统尚未充分复制这种反应性。本研究试图通过两个互补的目标来弥合这一鸿沟。第一种方法是制造配体支架，能够与质子化铜超氧化物单元形成低势垒氢键。这些独特的氢键相互作用所赋予的质子转移的额外热力学驱动力有望提高C-H键的活化反应活性。第二部分将寻求通过将超碱性官能团（共轭酸的pKa大于16）引入铜配合物的初级或次级配位球来改变厌氧条件下质子转移的热力学景观。后一种策略将通过使用机器学习来补充，以加速发现控制各种配体系统能力的关键因素，从而实现强C-H键激活。本提案中所描述的研究旨在产生所需的知识，以创建新型贱金属配合物，以高效和选择性地激活低分子量烷烃。这项工作有可能促进我们对关键C-H键活化化学的理解，同时指导未来与可再生能源经济相关的替代燃料的催化处理研究。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemical Synthesis program in the Division of Chemistry, Neil C. Tomson of the University of Pennsylvania will study the selective cleavage of C–H bonds, a grand challenge in chemistry. These notoriously unreactive bonds are widespread, from fossil fuels to plastics and other materials. The development of methods for splitting C-H bonds in a controlled manner is expected to aid in our fundamental understanding of their reaction chemistry and provide insight into how biological systems can perform these reactions with relative ease. These methods are also expected to enable technological developments, including the use of abundant feedstock chemicals, such as methane, for alternative fuels production. Trainees on this project will become skilled at performing highly air- and moisture-sensitive synthetic chemistry. This work will be supplemented by the use of modern computational chemistry techniques, which will provide an information-rich supplement to the synthetic chemistry being performed in the laboratory. The project will contribute to ongoing outreach efforts aimed at introducing high school students to themes in energy science. This effort will involve the creation of short videos that provide visual aids for explaining important aspects of chemistry in an accessible and captivating manner. The videos will highlight concepts covered within a high school curriculum and dovetail them with the alternative fuels focus of this research project.The activation of aliphatic C–H bonds is challenging for several reasons, including the need for a strong thermodynamic driving force for C–H bond cleavage. Copper ions, in combination with O2, are known to mediate strong C–H bond activation reactions in enzymes, but homogeneous systems have yet to adequately replicate this reactivity. This research seeks to bridge this divide through two complementary objectives. The first will create ligand scaffolds capable of engaging in low-barrier hydrogen bonds with a protonated cupric superoxide unit. The added thermodynamic driving force for proton transfer imparted by these unique hydrogen bonding interactions is expected to boost C–H bond activation reactivity. The second will seek to shift the thermodynamic landscape for proton transfer under anaerobic conditions by introducing superbasic functionalities (pKa of conjugate acid greater than 16) into the primary or secondary coordination spheres of cupric complexes. This latter strategy will be supplemented by the use of machine learning to accelerate the discovery of critical factors controlling the capacity of various ligand systems to enable strong C–H bond activation. The research described in this proposal is aimed at generating the knowledge needed to create new classes of base metal complexes for the efficient and selective activation of low molecular weight alkanes. This work has the potential to advance our understanding of critical C–H bond activation chemistry, while guiding future studies on the catalytic processing of alternative fuels relevant to a renewable energy economy.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.