Synchronous recognition of amines in oxidative carbonylation toward unsymmetrical ureas

Unsymmetrical ureas are commonly found in pharmaceuticals and bioactive compounds. However, devising strategies to introduce two distinct amines selectively in the construction of unsymmetrical ureas remains a challenge. In this work, we use a synchronous recognition strategy that takes advantage of radical and nucleophilic activation to discriminate between secondary and primary amines. Specifically, a copper catalyst preferentially oxidizes secondary amines to radical species, whereas a cobalt catalyst carbonylates primary amines to produce cobalt amides. Coupling these fragments by cooperative catalysis produces unsymmetrical ureas with high selectivity, as showcased by the modification of 41 biologically active compounds and six drugs.