The Synthesis and Reactivity of Carbamoyl Fluorides

Chapter 1 Herein we report a protocol for the synthesis of carbamoyl fluorides from secondary amines using inexpensive, and commercially available starting materials. This method employs the use of a difluorocarbene generated from the thermolysis of (triphenylphosphonio)difluoroacetate. This becomes oxidized by 4-methylpyridine N-oxide, generating difluorophosgene, which serves as the key intermediate to make the carbamoyl fluorides from secondary amine starting materials. This method allows access to carbamoyl fluorides with a vast functional group tolerance, including Lewis-basic heterocycles, alkenes, and alkynes.

Chapter 2 We report a base-free, facile cross-coupling reaction of carbamoyl fluorides to silylated nucleophiles. This reaction utilizes an affordable and Earth-abundant nickel transition metal catalyst, with a common phenanthroline ligand (both of which see an exceptionally low loading), to synthesize ureas, carbamates, and alkynamides in moderate to excellent yields. The transmetallation step of the purported catalytic cycle generates a fluorosilane, providing the thermodynamic driving force for the reaction to progress, and circumventing the requirement of base.