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Synlett 2010(15): 2345-2351  
DOI: 10.1055/s-0030-1258525
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Novel Indium-Catalyzed Three-Component Reaction: General and Efficient One-Pot Synthesis of Substituted Pyrroles

Min Lin*, Lu Hao, Rui-da Ma, Zhuang-ping Zhan
Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, Fujian, P. R. of China
Fax: +86(592)2180318; e-Mail: minlin@xmu.edu.cn;
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Publication History

Received 27 May 2010
Publication Date:
27 July 2010 (online)

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Abstract

A convenient and general approach towards the synthesis of substituted pyrroles from propargylic acetates, silyl enol ethers, and primary amines was described. This novel transformation was catalyzed by indium trichloride in a one-pot synthesis, and high yields of various pyrrole derivatives were obtained.

Key words

pyrrole - indium - one-pot reaction - propargylic acetate - enoxysilane

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General Experimental Methods
Propargylic acetates 1 and enoxysilanes 2 were prepared according to published procedures. All other compounds are commercially available and were used without further purification. Infrared spectra were recorded on a Nicolet AVATER FTIR360 spectrometer. NMR spectra were recorded on a Bruker AVANCE DPX-400 instrument at 400 MHz (¹H) or 100 MHz (¹³C). The chemical shift values (δ) are given in parts per million(ppm) and are referred to the residual peak of the deuterated solvent (CDCl3). MS measurements were performed on Bruker Reflex III mass spectrometer. Elemental analyses were performed with a PerkinElmer 2400 microanalyser. Flash chromatography was performed with QingDao silica gel (300-400 mesh).

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A Representative Procedure for the Synthesis of Substituted Pyrrole 2-Benzyl-1,3,5-triphenyl-1 H -pyrrole (6aa)
To a 10 mL flask, propargylic acetate 1a (0.5 mmol), enoxysilane 2a (1.0 mmol), chlorobenzene (2.0 mL), and InCl3 (0.05 mmol) were successively added. The reaction was allowed to stir at 75 ˚C for 0.5 h, followed by adding primary amines 7a (1.0 mmol). The reaction mixture was heated to keep refluxing for an additional 1 h until completion (monitored by TLC). Upon cooling to r.t., the reaction mixture was then quenched with 1 M HCl (2 mL). The organic and aqueous layers were separated, and the latter was extracted with Et2O (3 × 5 mL). The combined organic layers were dried over MgSO4 and filtered. The filtrate was concentrated in vacuo, and then the residue was purified by silica gel column chromatography (EtOAc-hexane, 1:100) to afford the corresponding substituted pyrroles. A yellow solid, mp 146-147 ˚C; yield 87% (0.167 g). ¹H NMR (400 MHz, CDCl3): δ = 7.50-7.52 (m, 2 H), 7.33-7.37 (m, 2 H), 7.07-7.24 (m, 12 H), 6.95-6.97 (m, 2 H), 6.88-6.90 (m, 2 H), 6.66 (s, 1 H), 4.04 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 140.5, 139.1, 136.9, 134.8, 133.2, 130.2, 129.0, 128.8, 128.7, 128.3, 128.2, 128.1, 128.0, 127.7, 126.1, 125.9 (3), 124.4, 109.6, 31.5 ppm. IR (film): 1493, 1599, 3024 cm-¹. ESI-MS: m/z (%) = 386 (100) [M + H+]. Anal. Calcd (%) for C29H23N: C, 90.35; H, 6.01; N, 3.63. Found: C, 90.38; H, 6.00, N, 3.63.