title: Orthogonal Cu- and Pd-based catalyst systems for the O- and N-arylation of aminophenols.
abstract: O- or 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 Cu- and Pd-based catalyst systems for the selective O- and N-arylation of unprotected aminophenols using aryl halides. Selective O-arylation of 3- and 4-aminophenols is achieved with copper-catalyzed methods employing picolinic acid or CyDMEDA, trans-N,N'-dimethyl-1,2-cyclohexanediamine, respectively, as the ligand. The selective formation of N-arylated products of 3- and 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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Maiti
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buchwald
mesh_terms: D000627:Aminophenols / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*
chemical_list: D000627:Aminophenols; D010165:Palladium; D003300:Copper