Air-Stable Palladium-Catalyzed Negishi Cross-Coupling Reactions

General Procedure for the Negishi Coupling Reactions

A solution of phenylmagnesium chloride (15 mL, 15 mmol, 1.0 M solution in THF) is treated with ZnCl2 (32 mL, 16 mmol, 0.5 M solution in THF) dropwise over a period of 5 min. The resulting mixture was stirred at room temperature for 20 min before 1-methyl-2-pyrrolidinone (NMP, 22 mL) was added. After the mixture was stirred for 5 more min., 250.0 mg (0.5 mm) of POPd, 1.43 g (10.0 mm) of 4-chloroanisol were added into the mixture above. The resulting mixture was refluxed for 2 h before it was cooled to room temperature, and aqueous HCl was added (1.0 M, 60 mL). The resulting mixture was extracted with Et2O (4 X 100 mL), and the extracts were washed with H2O (5 x 100 mL), and 100 mL of brine, then dried over MgSO4, filtered and concentrated by rotary evaporation. The crude product was purified by column chromatography on silica gel (95 : 5-hexane : diethyl ether) to afford 1.02 g (55% yield) of 4-phenylanisole.

Reference

1. J. Org. Chem. 2002, 67(11), 3643-3650. Li, George Y. “Highly Active, Air-Stable Palladium Catalysts for the C-C and C-S Bond-Forming Reactions of Vinyl and Aryl Chlorides: Use of Commercially Available [(t-Bu)2POH]2PdCl2, [(t-Bu)2P(OH)PdCl2]2 and {[(t-Bu)2PO•••H•••OP(t-Bu)2]PdCl}2 as Catalysts”.