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Synlett 2007(12): 1843-1850  
DOI: 10.1055/s-2007-984533
LETTER
© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalyzed Copper-Free Sonogashira Coupling Reaction in Water and Acetone

Shengyin Shi, Yuhong Zhang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
Fax: +86(571)87953244; e-Mail: yhzhang@zjuem.zju.edu.cn;
Further Information

Publication History

Received 11 April 2007
Publication Date:
27 June 2007 (online)

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Abstract

An efficient palladium-catalyzed copper-free Sono­gashira reaction in water and acetone has been developed under mild conditions. The results showed that the aryl iodides could carry out the cross-coupling reaction with a variety of terminal alkynes in high yields in water-acetone in the absence of amine, copper(I) salts, or phosphine ligands at 60 °C for one hour, and good yields were obtained for aryl bromides at 60 °C for 12-24 hours in the presence of triphenylphosphine and piperidine. The method could be used to synthesize polyethynyl aromatic compounds in a one-pot reaction.

Key words

copper-free - palladium-catalyzed - Sonogashira coupling - aqueous

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General Procedure for the Sonogashira Reaction of Aryl Iodides
A mixture of NaOH (0.08 g, 2 mmol), Pd(OAc)2 (2 mg, 1 mol%), distilled H2O (3 g), and acetone (3 g, 3.8 mL) was stirred for 5 min. Then, aryl iodides (1 mmol) and terminal alkynes (1.2 mmol) were introduced and the mixture of the reaction was heated to 60 °C for 1 h. Afterward, the reaction solution was cooled to r.t. and extracted four times with Et2O (4 × 10 mL). The combined organic phase was analyzed by GC and GC-MS. Further purification of the product was achieved by flash chromatography on a silica gel column.
1-(2-Phenylethynyl)naphthalene (Table [2] , entry 6): 1H NMR (500 MHz, CDCl3, TMS): δ = 8.43-8.45 (d, 1 H, J = 8.35 Hz), 7.72-7.80 (m, 3 H), 7.61-7.63 (m, 2 H), 7.55 (m, 1 H), 7.46-7.48 (m, 1 H), 7.33-7.38 (m, 1 H), 7.30-7.32 (m, 3 H). MS (EI): m/z (%) = 229 (20) [M+ + 1], 228 (100) [M+], 226 (43).

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General Procedure for the Sonogashira Reaction of Aryl Bromides and Polyhaloaryls
A mixture of piperidine (0.17 g, 2 mmol; for dihalides, 4 mmol; for trihalides, 6 mmol; for tetrahalides, 8 mmol), PdCl2 (11 mg, 5 mol%; for dihalides, PdCl2 = 10 mol%; for trihalides, PdCl2 = 15 mol%; for tetrahalides, PdCl2 = 20 mol%), PPh3 (26 mg, 10 mol%; for dihalides, PPh3 = 20 mol%; for trihalides, PPh3 = 30 mol%; for tetrahalides, PPh3 = 40 mol%), distilled H2O (3 g), and acetone (3 g, 3.8 mL) was stirred for 5 min under nitrogen. Then, aryl bromides or polyhaloaryls (1 mmol) and terminal alkynes (1.2 mmol; for dihalides, alkynes = 2.4 mmol; for trihalides, alkynes = 3.6 mmol; for tetrahalides, alkynes = 4.8 mmol) were introduced and the mixture of the reaction was heated to 60 °C for the indicated time under nitrogen. Afterwards, the reaction solution was cooled to r.t. and extracted with Et2O (4 × 10 mL). The combined organic phase was analyzed by GC and GC-MS. Further purification of the product was achieved by flash chromatography on a silica gel column.
1,4-Bis(2-phenylethynyl)benzene (Table [4] , entry 1): 1H NMR (500 MHz, CDCl3, TMS): δ = 7.52-7.54 (m, 4 H), 7.50 (s, 4 H), 7.34-7.36 (m, 6 H). MS (EI): m/z (%) = 279 (25) [M+ + 1], 278 (100) [M+], 139 (10).