Chemistry Weekly Seminar - Christine Le, York University

Title

Synthetic Strategies Leveraging Fluoride-Enabled Reactivity

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.

This seminar will discuss the preparation and synthetic utility of 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 despite their promising utility in fluoride-enabled transformations. The first part of the seminar will describe a new method to synthesize carbamoyl fluorides via the in-situ oxidation of difluorocarbene. The second part of the talk will explore the reactivity of carbamoyl fluorides in diverse synthetic transformations, such as cross-coupling, nucleophilic substitution, and halide recycling.

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, in press, DOI: 10.1021/acs.orglett.3c02871.

Time:    1:30 pm

Place:    Thorvaldson 159

Note:    Professor Le will be joining remotely.