D3SC: GOALI: Development of a Temperature Scanning Reaction Protocol for Pharmaceutical Catalytic Reaction Screening and Optimization

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In this GOALI (Grant Opportunities for Academic Liaison with Industry) project, supported by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Donna Blackmond at the Scripps Research Institute and Dr. Shashank Shekhar of AbbVie are developing new methods to study the rates and mechanisms of complex chemical reactions. This research addresses challenges and opportunities inherent in the modern study of complex organic reactions related to the pharmaceutical industry, which warrant an integrated approach in order to discover transformative solutions. The specific goal is to develop a new Temperature Scanning Reaction (TSR) protocol for monitoring chemical processes, which will be applicable in both industrial and academic laboratories. Reactions to be studied in detail are of broad interest in chemical synthesis but have complex kinetics and mechanisms. This new methodology enhances safety and efficiency by providing a deeper understanding of reaction processes and the mechanisms of chemical reactions. As a broader goal, this research provides a platform for future innovations in organic synthesis, synthetic methodology, catalysis, and reaction engineering. This project requires the development of new data-rich experimental tools and is partially funded through the Data-Driven Discovery Science in Chemistry (D3SC) initiative. Commensurate with the GOALI program requirements, the project involves an interdisciplinary team from Scripps and the four industrial partners Bristol Myers Squibb, Pfizer, Merck and Abbvie; this is expected to foster future collaboration between academic and industrial laboratories. Another major goal of this project is to provide training for graduate and undergraduate students, including experience in an industrial setting.With the expanding ability to monitor reactions in real time, and as the accuracy and data-density of measuring tools increases, chemists face the challenge of developing an integrated approach for data capture and interpretation, along with the creation of new reaction analysis tools. This project seeks to develop a novel Temperature-Scanning Reaction (TSR) protocol and reactors for streamlining the use of temperature as a variable kinetic parameter in reactions relevant to pharmaceutical process research. This approach is expected to advance: a) fundamental mechanistic study; b) rapid initial screening in pharmaceutical medicinal/discovery chemistry; and c) process optimization in pharmaceutical manufacture. The choice of reaction classes for these investigations is informed by current challenges in the pharmaceutical industry and chemical synthesis in general. Specific reaction classes include: a) asymmetric hydrogenation; b) electrocatalytic transformations; c) photoredox catalysis; and d) non-precious metal catalytic transformations. These studies aim to evaluate and develop this Temperature Scanning Reaction (TSR) approach in the context of Reaction Progress Kinetic Analysis (RPKA), a method developed earlier by the lead Principal Investigator. This research enhances safety and efficiency by providing an improved understanding of industrial reaction processes. New methodology for kinetic analysis can be broadly applied across chemistry to enhance fundamental mechanistic understanding. The pre-competitive nature of this project ensures that no intellectual property considerations will hamper the open discussion among industrial and academic participants.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.