GOALI: High Throughput Discovery and Optimization of Photochemical Reactions

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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.