LEAPS-MPS:'3-in-1' Catalysis - Decarboxylative Functionalization using a Single-Site Organophotocatalyst

In this project, funded by the MPS-LEAPS (Launching Early-Career Academic Pathways) Program and managed by the Division of Chemistry, Professor Alex Davies and his students at Western Michigan University will perform studies that aim to develop new multifunctional catalysts for radical decarboxylative functionalizations. Carboxylic acids are versatile chemical building blocks for synthesizing complex molecules due to their high stability, low toxicity and ubiquity in biomass. When used in conjunction with photoredox chemistry, highly reactive radical intermediates are formed from carboxylic acids upon loss of CO2, which can be harnessed to achieve a number of challenging bond formations. However, radical decarboxylations traditionally require three distinct catalytic components to i) activate the carboxylic acid through proton transfer, ii) oxidize the resulting carboxylate through single electron transfer and iii) facilitate cross-coupling with the radical species generated upon decarboxylation. To streamline this process, Professor Davies and his students will develop a multifunctional, organic photocatalyst capable of conducting all three of these roles independently. Their studies could lead to faster, more cost-effective decarboxylative cross-couplings that produce less waste and have broader functional group tolerance. This project will provide underrepresented students at Western Michigan University with hands on experience of chemical synthesis and compound characterization, as well as opportunities to connect with industrial collaborators and explore reaction scale up. Their work will also be integrated into the curriculum at the university through a Course-Based Undergraduate Research Experience, focusing on making photochemistry accessible to undergraduate students. Professor Davies and his students will employ a strategically designed quinoline catalyst toward a series of decarboxylative cross-coupling reactions. By leveraging a typically undesirable degradation pathway of similar photoactive compounds, these catalysts can utilize carboxylic acids as functional handles for decarboxylative protonation (C-H bond forming), decarboxylative oxidation (C=O bond forming) and a metal-free, decarboxylative alkylation strategy (C(sp3)-C(sp3) bond-forming). This project involves elucidating the underlying mechanisms of action to help guide future catalyst design, enhancing catalytic efficiency through strategic structural modifications, and adapting their protocol for industrial scale synthesis using flow technology. Ultimately, the data generated from this project may be broadly applied to design other metal-free cross-coupling reactions. 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.