Palladium-Catalyzed Cross-Coupling of Electron-Deficient Heteroaromatic Amines with Heteroaryl Halides

Abstract

An efficient method has been developed for the Pd-catalyzed cross-coupling reactions of electron-deficient heteroaromatic amines with heteroaryl halides. The optimized reactions used Pd₂(dba)₃ as catalyst, 1,1′-bis(diphenylphosphino)ferrocene (DPPF) as ligand, and Cs₂CO₃ as base. The Pd-catalyzed cross-coupling reactions of several rarely reported electron-deficient heteroaromatic amines were successfully accomplished in good yields.

GRAPHICAL ABSTRACT

Keywords:

• Buchwald–Hartwig reaction
• heteroaromatic amines
• heteroaryl halides
• Pd-catalyzed cross-coupling

ACKNOWLEDGMENTS

The authors thank the Global Alliance for TB Drug Development and the National Science and Technology Project of China (No. 2009ZX09102-054) for financial support of this project.

Notes

^a Reaction conditions: 1a (1.0 equiv, 2.0 mmol), 1b (1.5 equiv), catalyst (2 mol%), ligand (8 mol%), base (1.5 equiv).

^b The products were purified by flash silica-gel chromatography.

^c All yields are reported for isolated and purified products.

^d IPr · HCl, 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride.

^a Reactions run with 2.0 mmol of heteroaromatic amine in 20 mL of toluene solvent at 110 °C. Pd₂(dba)₃ was used in combination with 4.0 equiv of ligand/Pd.

^b The products were purified by flash silica-gel chromatography.

^c Isolated yields are an average of at least two runs.

^d The yield was reported in the literature under different reaction conditions from that of Ref.^{[ 13 ]}