Orthogonal Cu - and Pd - Based Catalyst Systems for the O - and N - Arylation

Oor N-arylated aminophenol products constitute a common structural motif in various potentially useful therapeutic agents and/or drug candidates. We have developed a complementary set of Cuand Pd-based catalyst systems for the selective Oand N-arylation of unprotected aminophenols using aryl halides. Selective O-arylation of 3and 4-aminophenols is achieved with copper-catalyzed methods employing picolinic acid or CyDMEDA, trans-N,N′-dimethyl-1,2cyclohexanediamine, respectively, as the ligand. The selective formation of N-arylated products of 3and 4-aminophenols can be obtained with BrettPhos precatalyst, a biarylmonophosphine-based palladium catalyst. 2-Aminophenol can be selectively N-arylated with CuI, although no system for the selective O-arylation could be found. Coupling partners with diverse electronic properties and a variety of functional groups can be selectively transformed under these conditions.