An Efficient and Scalable Approach to Functionalized Urea via Bench-Stable Amidine Building Blocks

Urea derivatives are privileged structural motifs in pharmaceuticals, organocatalysts, and functional materials due to their exceptional hydrogen-bonding capabilities. Classical synthetic strategies for ureas typically rely on the reaction of amines with phosgene or its derivatives─reagents that are highly toxic, moisture-sensitive, and require stringent handling conditions. Herein, we report a thiol-catalyzed, efficient, and scalable approach to access structurally diverse urea derivatives via bench-stable, nonvolatile, and isolable amidine building blocks. These key intermediates can be readily prepared from trichloroacetonitrile and amines under solvent-free conditions, offering operational simplicity and excellent functional group tolerance. This strategy not only avoids the use of safety-sensitive reagents but also enables broad substrate scope, including sterically hindered, chiral, and bioactive amines, thus providing a practical and sustainable platform for the synthesis of high-value urea-containing molecules.