Synthetic strategies leveraging fluoride-enabled reactivity
Christine Le
Assistant Professor, Department of Chemistry
York University
Tuesday, October 8, 2024
11 a.m.
In-person: C2-361
Abstract: The high strength and polarity of C–F bonds gives rise to many of the desirable properties of fluorinated pharmaceuticals, agrochemicals, polymers, and functional materials. However, these defining characteristics also make fluorinated compounds difficult to functionalize, often requiring the use of specialized catalysts or reagents to effect C–F bond cleavage under mild conditions. Notwithstanding these inherent challenges, the use of C–F bond electrophiles can offer distinct synthetic advantages, such as enabling unique reactivity when paired with an appropriate fluorophilic catalyst or permitting chemoselective transformations of polyhalogenated substrates. Over the past few years, my group has explored the preparation and synthetic utility carbamoyl fluorides, an emerging class of electrophiles that can provide entry to medicinally important amides and N-heterocycles through C–F bond functionalization. Although the chemistry of the analogous carbamoyl chlorides has been extensively developed, synthetic applications of carbamoyl fluorides remain underexplored. In this presentation, I will discuss the application of carbamoyl fluorides in diverse synthetic transformations, such as cross-coupling, nucleophilic substitution, and halide recycling. Mechanistic studies involving reaction kinetics, intermediate isolation, and DFT calculations will be presented to support the role of fluoride in promoting reactivity and/or selectivity in the developed transformations.
Key references:
- Cadwallader, D.; Tiburcio, T. R.; Cieszynski, G. A.; Le, C.M.* J. Org. Chem. 2022, 87, 11457–11468.
- McKnight, A. E.; Arora, R.; Pradhan, E.; Fujisato, Y. H.; Ajayi, A. J.; Lautens, M.; Zeng, T.;* Le, C.M.* J. Am. Chem. Soc. 2023, 145, 11012–11018.
- Cadwallader, D.; Shevchuk, D.; Tiburcio, T. R.; Le, C.M.* Org. Lett. 2023, 25, 7369–7373.
- Jabbarpoor, M.; LeBlanc, J.; Chen, Z.; Cadwallader, D.; Le, C. M.* Chem. Commun., 2024, 60, 8700–8703.
Christine Le is an Assistant Professor at York University in Toronto (Canada). She received her BSc from Western University (2011), and her MSc (2012) and PhD degrees (2016) from the University of Toronto in the labs of Professor Vy Dong and Professor Mark Lautens, respectively. In 2017, Christine moved to UC Berkeley as an NSERC Postdoctoral Fellow, working under the guidance of Professor F. Dean Toste. Christine has been the recipient of several awards and recognitions throughout her early career, such as the NSERC Julie Payette Scholarship, the Boehringer Ingelheim Award of Excellence in Organic Chemistry, Forbes 30 Under 30 Science, the Petro-Canada Emerging Innovator Award, and 2024 Thieme Chemistry Journal Awardee. Her current research program focuses on the synthesis of fluorinated building blocks and their application in fluoride-enabled transformations. More information about the Le Group.
