Palladium-Catalyzed N-Arylation of 2-Aminothiazoles

Reaction Scheme

Abstract

The chemoselective and complementary Pd- and Cu-catalyzed N-arylation of 2-aminobenzimidazoles is described. Selective N-arylation of the amino group was achieved with a Pd-catalyzed method, while selective N-arylation of azole nitrogen was achieved with a Cu-catalyzed procedure

Substrates

Procedure

An oven-dried vial was equipped with a magnetic stir bar and charged with Pd2(dba)3 (2.3 mg, 0.0025 mmol) and Me4tBuXPhos (2.4 mg, 0.005 mmol). The vial was sealed with a screw-cap septum, and then evacuated and backfilled with argon (this process was repeated a total of 3 times). Anhydrous t-BuOH (0.3 mL) was added via syringe and the resulting dark purple mixture was stirred at 120 �C for 3 min, at this point the color of the mixture turned to red-brown. A second oven-dried vial, which was equipped with stir bar, was charged with aminoazole (1.1 mmol) and K3PO4 (318 mg, 1.5 mmol) (aryl halides that were solid at room temperature were added at this point). The vial was sealed with a screw-cap septum, and then evacuated and backfilled with argon (4 psi) (this process was repeated a total of 3 times). Aryl halide (1.0 mmol) and the pre-heated catalyst solution (0.12-0.3 mL, 0.2-0.5 mol% Pd) were added by syringe to the second vial, followed by addition of t-BuOH (1.5 mL). The reaction mixture was heated at 120 �C for 5 h. The reaction mixture was cooled to room temperature, diluted with EtOAc, washed with brine and dried over MgSO4. Silica gel (1.0 g) was added to the mixture and the mixture was concentrated in vacuo. The Silica gel-adsorbed product was purified via flash chromatography

Products

Materials

     
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