Facile Synthesis of Carbamoyl Fluorides via N-Carbamoylimidazole Activation

The untapped potential of carbamoyl fluorides for various chemico/biological applications is hampered by the scarcity of straightforward and benign methods for their synthesis. In this report, we disclose a novel mild three-step procedure that avoids exotic, corrosive, and highly toxic reagents. Briefly, commercially available secondary amines are carbamoylated with 1,1′-carbonyldiimidazole, followed by alkylation to improve nucleofugality, and exchange with inorganic KF. This procedure works on a gram scale without chromatographic purification. It is however limited to basic, sterically unhindered secondary amines without alkylation-prone functional groups.