Orthogonal Cu- and Pd-Based Catalyst Systems for the O- and N-Arylation of Aminophenols
Author(s)Maiti, Debabrata; Buchwald, Stephen Leffler
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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.
DepartmentMassachusetts Institute of Technology. Department of Chemistry
Journal of the American Chemical Society
American Chemical Society (ACS)
Maiti, Debabrata, and Stephen L. Buchwald. “Orthogonal Cu- and Pd-Based Catalyst Systems for the O- and N-Arylation of Aminophenols.” Journal of the American Chemical Society 131, no. 47 (December 2, 2009): 17423-17429.
Author's final manuscript