Synlett 2005(16): 2425-2428  
DOI: 10.1055/s-2005-872688
LETTER
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted Addition of Pyrroles to Electron-Deficient Olefins: A Rapid Entry to C-Alkyl Pyrroles

Zhuang-Ping Zhan*, Wen-Zhen Yang, Rui-Feng Yang
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P. R. of China
Fax: +86(592)2185780; e-Mail: zpzhan@xmu.edu.cn;
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Publikationsverlauf

Received 13 May 2005
Publikationsdatum:
21. September 2005 (online)

Abstract

A general procedure for the Michael addition of pyrroles with electron-deficient olefins using silica gel supported reagent under microwave irradiation, has been developed. This new method is fast, efficient, environmentally benign and solvent-free. A catalytic amount of BiCl3 is employed for moderately bulk electron-deficient olefins.

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Typical Experimental Procedure.
Catalyst-free: To a solution of pyrrole (2 mmol) or N-benzyl pyrrole (2 mmol) or 2-alkylpyrroles (1 mmol) in CH2Cl2 (1 mL) was added electron-deficient olefin (1 mmol for pyrrole and N-benzyl pyrrole, 1.2 mmol for 2-alkylpyrroles) and silica gel (0.25 g). Then the mixture was mixed thoroughly and dried under reduced pressure. The contents were taken in a 5 mL conical flask and was placed in a microwave oven (cooking type, Galanz WP 700P 21-6) and irradiated for 1-4 min at 680 W. After completion of the reaction indicated by TLC, the reaction mixture was allowed to cool, diluted with CH2Cl2 and passed through a short silica gel column using CH2Cl2 as eluent. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography to afford the corresponding 2-alkylpyrroles or 2,5-dialkylpyrroles.
Spectral data for selected compound. 4-(1 H -Pyrrol-2-yl)butan-2-one (a): yield 123 mg (90%). IR (film): 3377, 1707 cm-1. 1H NMR (500 MHz, CDCl3):
δ = 2.17 (s, 3 H), 2.81 (t, J = 6.5 Hz, 2 H), 2.87 (t, J = 6.5 Hz, 2 H), 5.90 (s, 1 H), 6.10 (d, J = 3.0 Hz, 1 H), 6.66 (d, J = 3.0 Hz, 1 H), 8.54 (br, 1 H). 13C NMR (125 MHz, CDCl3): δ = 21.2, 30.0, 44.0, 105.1, 107.7, 116.6, 131.4, 209.6. ESI-MS: m/z (%) = 138 (100) [M + H+], 160 (48) [M + Na+]. Anal. Calcd for C8H11NO: C, 70.04; H, 8.08; N, 10.21. Found: C, 70.02; H, 8.12; N, 10.07.
Using 5% mol BiCl3 as catalyst: to a solution of BiCl3 (0.05 mmol) in MeCN (1 mL) was added pyrrole (2 mmol) or N-benzyl pyrrole (2 mmol) or 2-alkylpyrroles (1 mmol), followed by electron-deficient olefins (1 mmol for pyrrole and N-benzyl pyrrole, 1.2 mmol for 2-alkylpyrroles) and silica gel (0.25 g). Then the mixture was mixed thoroughly and dried under reduced pressure. For the following work up see typical experimental procedure (a).

Spectral data for selected compound.
3-[5-(3-Oxo-3-phenylpropyl)-1 H -pyrrol-2-yl]cyclo-hexanone (f): yield 259 mg (88%). IR (film): 3373, 1708, 1677, 1595, 1579 cm-1. 1H NMR (500 MHz, CDCl3): δ = 1.72-2.69 (m, 8 H), 3.01 (t, J = 6.0 Hz, 2 H), 3.04-3.11 (m, 1 H), 3.33 (t, J = 6.0 Hz, 2 H), 5.79 (d, J = 2.5 Hz, 1 H), 5.83 (d, J = 2.5 Hz, 1 H), 7.44-8.04 (m, 5 H), 8.52 (br, 1 H). 13C NMR (125 MHz, CDCl3): δ = 21.5, 24.8, 31.6, 37.4, 39.4, 41.2, 47.4, 103.4, 105.2, 128.0, 128.6, 130.9, 133.4, 133.7, 136.6, 200.9, 210.9. ESI-MS: m/z (%) = 296 (100) [M + H+], 318 (95) [M + Na+]. Anal. Calcd for C19H21NO2: C, 77.14; H, 7.05; N, 4.67. Found: C, 77.26; H, 7.17; N, 4.74.