Pd/Cu-Catalyzed Vinylation of Terminal Alkynes with (2-Bromoethyl)diphenylsulfonium Triflate

Xiao-Xia Ming, Shuai Wu, Ze-Yu Tian, Jia-Wei Song and Cheng-Pan Zhang*

*School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, Hubei 430070, China, Email: cpzhangwhut.edu.cn

X.-X. Ming, S. Wu, Z.-Y. Tian, J.-W. Song, C.-P. Zhang, Org. Lett., 2021, 23, 6795-6800.

DOI: 10.1021/acs.orglett.1c02379

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Abstract

(2-Bromoethyl)diphenylsulfonium triflate and diphenyl(vinyl)sulfonium triflate are powerful vinylation reagents for Sonogashira cross-coupling reactions with terminal alkynes. The vinylations proceed smoothly at 25 °C under Pd/Cu catalysis to afford various 1- and 2-unsubstituted 1,3-enynes in good yields.

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General procedures for vinylation of terminal alkyne with (2-bromoethyl) diphenylsulfonium triflate:

Procedure A (one-pot reactions, for products with low boiling points only): In a nitrogen filled glovebox, a sealed tube was charged with Pd(PPh₃)₄ (0.01 mmol), CuI (0.01 mmol), (2-bromoethyl)diphenylsulfonium triflate (133.0 mg, 0.3 mmol), terminal alkyne (0.2 mmol), K₃PO₄ (63.7 mg, 0.3 mmol), and DME (2 mL) with vigorous stirring. The mixture was reacted at 25°C for 12 h, diluted with diethyl ether (10 mL), and washed with H₂O (15 mL). The aqueous solution was extracted with diethyl ether (10 mL). The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated to dryness under reduced pressure at ca. 10 °C. The residue was purified by column chromatography on silica gel using pentane as eluent to give the desired product.

Procedure B (one-pot reactions): In a nitrogen filled glovebox, a sealed tube was charged with Pd(PPh₃)₄ (0.01 mmol), CuI (0.01 mmol), (2-bromoethyl)diphenylsulfonium triflate (133.0 mg, 0.3 mmol), terminal alkyne (0.2 mmol), K₃PO₄ (63.7 mg, 0.3 mmol), and DME (2 mL) with vigorous stirring. The mixture was reacted at 25°C for 12 h and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether or a mixture of petroleum ether (or hexane) and ethyl acetate as eluents to give the desired product.

Procedure C (stepwise reactions, for products with low boiling points only): In a nitrogen filled glovebox, a sealed tube was charged with (2-bromoethyl)diphenylsulfonium triflate (133.0 mg, 0.3 mmol), K₃PO₄ (63.7 mg, 0.3 mmol), and DME (1 mL) with vigorous stirring. The mixture was reacted at 25°C for 20 mins. Then, Pd(PPh₃)₄ (0.01 mmol), CuI (0.01 mmol), terminal alkyne (0.2 mmol), and DME (1 mL) were added. The resulting mixture was reacted at 25°C for another 12 h, diluted with ethyl ether (10 mL), and washed with H₂O (15 mL). The aqueous solution was extracted with ethyl ether (10 mL). The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated to dryness under reduced pressure at ca. 10°C. The residue was purified by column chromatography on silica gel using pentane as eluent to give the desired product .

Procedure D (stepwise reactions): In a nitrogen filled glovebox, a sealed tube was charged with (2-bromoethyl)diphenylsulfonium triflate (133.0 mg, 0.3 mmol), K₃PO₄ (63.7 mg, 0.3 mmol), and DME (1 mL) with vigorous stirring. The mixture was reacted at 25°C for 20 mins. Then, Pd(PPh₃)₄ (0.01 mmol), CuI (0.01 mmol), terminal alkyne (0.2 mmol), and DME (1 mL) were added. The resulting mixture was reacted at 25°C for another 12 h and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether or a mixture of petroleum ether (or hexane) and ethyl acetate as eluents to give the desired product.

General procedures for vinylation of terminal alkyne with diphenyl(vinyl) sulfonium triflate:

Procedure A (for products with low boiling points only): In a nitrogen filled glovebox, a sealed tube was charged with Pd(PPh₃)₄ (0.01 mmol), CuI (0.01 mmol), diphenyl(vinyl)sulfonium triflate (87.0 mg, 0.24 mmol), terminal alkyne (0.2 mmol), K₃PO₄ (42.5 mg, 0.2 mmol), and DME (2 mL) with vigorous stirring. The mixture was reacted at 25°C for 12 h, diluted with diethyl ether (10 mL), and washed with H₂O (15 mL). The aqueous solution was extracted with diethyl ether (10 mL). The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated to dryness under reduced pressure at ca. 10 °C. The residue was purified by column chromatography on silica gel using pentane as eluent to give the desired product.

Procedure B: In a nitrogen filled glovebox, a sealed tube was charged with Pd(PPh₃)₄ (0.01 mmol), CuI (0.01 mmol), diphenyl(vinyl)sulfonium triflate (87.0 mg, 0.24 mmol), terminal alkyne (0.2 mmol), K₃PO₄ (42.5 mg, 0.2 mmol), and DME (2 mL) with vigorous stirring. The mixture was reacted at 25°C for 12 h and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether or a mixture of petroleum ether and ethyl acetate as eluents to give the desired product.

Key Words

1,3-Enynes, Sonogashira Coupling

ID: J54-Y2021