Dr. Christine Le

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 challenging 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 challenging bond-breaking/forming events 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–C bond coupling. Although the chemistry of the analogous carbamoyl chlorides has been extensively developed, synthetic applications of carbamoyl fluorides remain underexplored, despite their potential to exploit unique fluoride-enabled reactivity. The first part of the seminar will discuss 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 cycloisomerization via novel “halide recycling” mechanism.