Merging Photoredox with Nitro Reduction for the Direct Synthesis of Unsymmetrical Ureas

Unsymmetrical ureas represent a challenging structural motif of high pharmaceutical relevance, yet direct and convergent syntheses remain limited. Herein, we present a unified photoredox strategy that constructs the unsymmetric urea linkage in a single step from two stable, commercially abundant feedstocks: nitroarenes and N-aryl 2-oxoacetamides. Enabled by a simple flavin catalyst under visible blue light, the reaction proceeds via a tandem nitro reduction-decarboxylation-ureidation sequence without the need for preformed amines, phosgene derivatives, or stoichiometric activators. Mechanistic studies support the intermediacy of nitrosoarene and 1-hydroxy-1-phenyl-3-(p-tolyl)urea species during the transformation. The protocol exhibits broad substrate scope and excellent functional group tolerance, operates under mild conditions, and provides a step-economical route to a wide range of unsymmetric ureas in up to 96% yields.