GOALI: High Throughput Discovery and Optimization of Photochemical Reactions

在化学系化学催化项目的资助下，密歇根大学安娜堡分校的科里·斯蒂芬森教授和罗伯特·肯尼迪教授正在将最先进的高通量实验技术与光驱动光化学催化相结合。该项目的成功将为合成更高效、更可持续的有机分子提供新的方法。这些技术的指导原则将加速合成高价值分子的方法，如药物构建块，同时与传统化学相比减少浪费和环境足迹。光化学利用光作为形成新化学键的驱动力。这种方法通常能够形成独特的键，而通过简单的加热是无法获得的。尽管光化学具有很高的潜力，但高效开发和优化光化学的技术已经落后于大规模的热方法。在这个项目中，斯蒂芬森博士和肯尼迪博士正在研究使光化学系统适应低浪费、高通量的微流控技术，以开发新的工艺并最终实现大规模应用。这项研究项目是与AbbVie工艺研究和开发团队合作进行的，使新方法能够简化合并，立即应用到大规模的药物中间体合成中。此外，斯蒂芬森和肯尼迪的研究小组还参与了几个外展项目，吸引小学(3-12年级)的学生，目的是激励下一代科学领袖。斯蒂芬森参与了密歇根大学数学、工程和科学(FETMES)和密歇根数学和科学学者(MMSS)项目的女性，这使得小学生能够在一个有趣和支持的氛围中直接参与合成化学，同时也鼓励他们追求科学事业。这项由密歇根大学斯蒂芬森和肯尼迪小组与AbbVie过程化学小组合作的研究将使液滴微流控技术适应化学合成中光化学方法的快速发展。液滴微流控系统是一种最先进的高通量实验技术(HTE)，可将规模缩小1000倍以上，同时比当前的HTE方法提高吞吐量。这一微流控平台将促进新的光化学方法的快速优化，同时允许直接转换为可扩展的流动化学方法。此外，这里提出的微流控技术的发展有可能为正在研究的反应提供动力学和机械方面的见解，即使是在皮摩尔尺度上也是如此。为了详细了解反应机理，将与AbbVie过程研究和开发团队合作，开发一种新的流动过程进行机械分析的方法，其中成功的候选反应可以快速转化为工业规模。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With funding from the Chemical Catalysis program of the Division of Chemistry, Professors Corey Stephenson and Robert Kennedy at the University of Michigan–Ann Arbor are merging state-of-the-art, high-throughput experimentation technology with light-driven photochemical catalysis. Success in this project will provide new methods for the synthesis of organic molecules that are more efficient and sustainable. The guiding principles of these technologies will accelerate methods to synthesize high value molecules such as pharmaceutical building blocks while simultaneously reducing the waste and environmental footprint as compared to traditional chemistries. Photochemistry uses light as the driving force to form new chemical bonds. This approach often enables the formation of unique bonds not accessible through simple heating. Despite its high potential, technologies for efficient development and optimization of photochemistry have trailed behind thermal methods at large scale. In this project, Dr. Stephenson and Dr. Kennedy are studying the adaptation of photochemical systems to low-waste, high-throughput microfluidic technology for the development of new processes and eventual large scale application. This research project is carried out in collaboration with the AbbVie Process Research and Development team, allowing for the streamlined incorporation of the new methods to be immediately implemented into the large scale synthesis of pharmaceutical intermediates. Additionally, the Stephenson and Kennedy research groups are involved in several outreach programs that engage grade school (3rd-12th grade) students, with the intention of inspiring the next generation of scientific leaders. Stephenson’s involvement in the Females Excelling More in Mathematics, Engineering, and the Science (FEMMES) and the Michigan Math and Science Scholars (MMSS) programs at the University of Michigan has allowed for the direct engagement of grade school students with synthetic chemistry in a fun and supportive atmosphere, while also encouraging them to pursue careers in science.This collaborative research between the Stephenson and Kennedy groups at the University of Michigan and the AbbVie Process Chemistry group will adapt droplet microfluidic technology to the rapid development of photochemical methods in chemical synthesis. Droplet microfluidic systems are a state-of-the-art high throughput experimentation technology (HTE) offering upwards of a 1000-fold reduction in scale while simultaneously increasing throughput over current HTE methods. This microfluidic platform will facilitate the rapid optimization of new photochemical methodology while allowing for a direct translation to scalable chemistry-in-flow approaches. Furthermore, the developments in microfluidic technology proposed herein have the potential to provide for kinetic and mechanistic insights into the reactions under study even at the picomole scale. To gain a detailed understanding of reaction mechanism, methods will be developed for a novel in-flow process for mechanistic analysis, in collaboration with the AbbVie Process Research and Development team, where successful candidate reactions can be rapidly translated to industrial scale.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.