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Synlett 2009(5): 828-832  
DOI: 10.1055/s-0028-1087952
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Easy One-Pot Synthesis of Tetrasubstituted 3-Alkynylpyrroles via Multicomponent Coupling Reaction

Xueming Chena, Lei Houb, Xingshu Li*a
a School of Pharmaceutical Science, Sun Yat-Sen University, Guangzhou, 51006, P. R. of China
Fax: +86(20)39943050; e-Mail: lixsh@mail.sysu.edu.cn;
b MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, 510275, P. R. of China
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Publication History

Received 28 October 2008
Publication Date:
24 February 2009 (online)

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Abstract

A series of tetrasubstituted 3-alkynylpyrroles were synthesized via a three-component reaction of imines, phenylacetylene, and dialkylzinc. This method provided a new strategy for preparing tetrasubstituted 3-alkynylpyrroles which can be converted into more complex molecules.

Key words

multicomponent reactions - pyrroles - tetrasubstituted 3-alkynylpyrroles

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The CCDC number: 706290.

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General Procedure for the Preparation of Imines To a round-bottomed flask containing the amine (10 mmol) in toluene (20 mL) was added anhyd Na2SO4 (50 mmol). The mixture was stirred, and then ethyl glyoxalate (12 mmol) was added slowly. After the reaction was completed (about 1 h, monitored by TLC), Na2SO4 was removed by filtration, and toluene was distilled under reduced pressure to yield the crude imine (95% yield), which was used for the next step without purification.
General Procedure for the Preparation of Pyrrole Derivatives
To a flask containing phenylacetylene (6 mmol), a 1.2 M solution of Me2Zn in toluene (6 mmol) was added at r.t. The resulting solution was stirred for 1 h, and then the imine
(1 mmol) in toluene (1 mL) was added at the same temperature. The reaction mixture was stirred for 5 h. After the reaction was completed (monitored by TLC), it was quenched by addition of H2O (5 mL). The mixture was diluted with Et2O, stirred for 5 min, and then filtered through Celite. The collected filtrate was separated, and the aqueous phase was extracted with Et2O (3 × 3 mL). The combined organic phases were washed with brine and dried over Na2SO4. After removal of the solvent under reduced pressure, the crude product was purified by flash column chromatography (eluent: EtOAc-PE, 1:50) to afford the desired pyrrole products.
2-Methyl-5-phenyl-3-(phenylethynyl)-1- p -tolyl-1 H -pyrrole (1a) White solid. ¹H NMR (300 MHz, CDCl3): δ = 2.34 (s, 3 H), 2.43 (s, 3 H), 6.60 (s, 1 H), 7.07-7.10 (d, 2 H), 7.16-7.19 (m, 7 H), 7.32-7.41 (m, 3 H), 7.57-7.60 (d, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 12.75, 21.63, 85.48, 90.72, 103.35, 111.27, 124.78, 126.47, 127.56, 128.28, 128.50, 130.02, 131.47, 132.93, 134.07, 136.40, 136.51, 137.97. HRMS:
m/z calcd for C26H21N [M+]: 347.1679; found: 347.1680.