A General, Practical Palladium-Catalyzed Cyanation of (Hetero)Aryl Chlorides and Bromides

Reaction Scheme

Abstract

The nontoxic cyanide source K4[Fe(CN)6]�3H2O can be used for the cyanation of (hetero)aryl halides. The application of palladacycle catalysts prevents poisoning during catalyst formation, thereby allowing for low catalyst loadings, fast reaction times, and wide heterocyclic substrate scope.

Substrates

Procedure

To a screw-top test tube equipped with a magnetic stir bar was added precatalyst, ligand, K4[Fe(CN) 6]�3H2O (211 mg, 0.5 equiv.), and (if solid) (hetero)aryl halide (1 mmol). After sealing with a Teflon-lined screw-cap septum, the vessel was evacuated and backfilled with nitrogen (this process was repeated for a total of three cycles). (Hetero)aryl halide (if liquid) (1 mmol), dioxane (2.5 mL), and 0.05 M KOAc in degassed water (2.5 mL) were then added to the reaction tube via syringe. The test tube was placed in an oil bath preheated to 100 �C and stirred for 1 h. Upon initial stirring, a clear, yellow solution was observed. During the course of the reaction, a yellow or green precipitate formed on the walls of the reaction vessel. After 1 h of stirring at 100 �C, the reaction mixture was then cooled to room temperature. The contents of the test tube were transferred to a separatory funnel using EtOAc (15 mL) and brine (15 mL), and the organic layer was separated from the aqueous layer. If the reaction was successful, during the extraction process the color of the aqueous layer turns dark blue. This is a colloidal suspension of insoluble fine particles. Isolation and PXRD analysis revealed this solid to be Prussian Blue. The aqueous layer was further extracted with EtOAc (total 2 x 15 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The resulting mixture was adsorbed onto silica gel, dried in vacuo, and purified via column chromatography to yield the product.

Products

Materials

     
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