Deprotective Lossen rearrangement: a direct and general transformation of Nms-amides to unsymmetrical ureas

Ureas stand out as potent pharmacophores in drug development, rendering them a prime focus for synthesis. Herein, we present an appealing entry point for urea synthesis from protected amines (Nms-amides) and relying on a Lossen-type rearrangement process as an elegant example of deprotective functionalisation. The method developed exhibits an exceptionally broad tolerance towards various protected amines, encompassing numerous drug derivatives, and delivers high reaction yields. Herein, we report the development of a deprotective functionalisation reaction that allows for the synthesis of unsymmetrical ureas through a Lossen-type rearrangement of Nms-protected amines.