The Room-Temperature Palladium-Catalyzed Cyanation of Aryl Bromides and Iodides with Tri-t-butylphosphine as Ligand

Abstract

The palladium-catalyzed cyanation of aryl bromides and iodides to the corresponding nitriles occurs at room temperature when tri-t-butylphosphine is used as ligand, Zn(CN)₂ as the cyanide source and Zn dust as a co-catalyst in DMF as solvent. A variety of aromatic halides, including electron-withdrawing and electron-donating, can be efficiently cyanated under these conditions. The reactions are completed in less than 1 hour and products are produced in good to excellent yield.

palladium-catalyzed - cyanation - aryl iodide - aryl bromide - tri-t-butylphosphine.

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11

General Procedure: An oven-dried, Ar-purged, round bottom flask was charged with the aryl halide (0.5 mmol), Zn(CN)₂ (0.9 mmol), Pd₂(dba)₃ (0.013 mmol), and Zn dust (0.06 mmol) followed by DMF (5 mL). The ligand (10 wt% in hexane, 0.025 mmol) was added and the reaction mixture was rapidly stirred at r.t. for 1 h. After this time, the mixture was partitioned between 20 mL EtOAc and 10 mL H₂O. The EtOAc layer was separated, washed with brine (10 mL) and dried over MgSO₄. After concentration, the residue was subjected to silica gel column chromatography using a hexane-EtOAC solvent system to furnish the aryl nitrile. Spectroscopic data and melting points were consistent with known values.