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Synlett 2012(5): 751-754  
DOI: 10.1055/s-0031-1290605
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Friedel-Crafts Alkylation of Indoles by tert-Enamides in Acetic Acid

Ying Zhang, Jing Jiang, Xue-Qiang Chu, Ran Jiang, Xiao-Ping Xu*, Dan-Hua Li, Shun-Jun Ji*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. of China
Fax: +86(512)65880307; e-Mail: xuxp@suda.edu.cn; e-Mail: chemjsj@suda.edu.cn;
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Publication History

Received 14 November 2011
Publication Date:
28 February 2012 (online)

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Abstract

In acetic acid, Friedel-Crafts alkylation of indoles by tert-enamides proceeded effectively in the absence of any catalyst to afford the pharmacologically and biologically active 2-oxo-1-pyrrolidine derivatives in moderate to good yields. The mechanistic study based on the NMR and HRMS analysis shows that the reaction was promoted by acid catalysis. The hydrogen-bond interaction between tert-enamides and AcOH may also be responsible for the reaction.

Key words

acetic acid - Friedel-Crafts alkylation - tert-enamide - indole

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13

General Procedure for the Reaction of N -Vinyl Compound with Nucleophile (Take the Reaction of 1-Vinylpyrrolidin-2-one with Indole as Example) To a mixture of 1-vinylpyrrolidin-2-one (0.1111g, 1.0 mmol) and indole (0.1171g, 1.0 mmol), AcOH (1.0 mL) was added. The reaction system was stirred vigorously at r.t. until the starting materials were completely consumed as indicated by TLC analysis. Then the mixture was poured into H2O, neutralized by NaHCO3, and extracted by CH2Cl2 (2 × 15 mL). The combined organic layer was washed with brine, dried with anhyd Na2SO4, and evaporated under the reduced pressure. The residue was purified by flash column chromatography with EtOAc and PE as eluents to afford pure product 3aa (0.194 g, yield 85%).
1-[1-(2-Methyl-1 H -indol-3-yl)ethyl]pyrrolidin-2-one (3ab) White solid; mp 176-177 ˚C. IR (KBr): 3317, 2974, 2933, 2876, 1656, 1491, 1435, 1287, 1198, 1051, 749 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 1.72 (d, J = 6.9 Hz, 3 H), 1.82-2.00 (m, 2 H), 2.32-2.41 (m, 2 H), 2.48 (s, 3 H), 3.11-3.19 (m, 1 H), 3.53-3.61 (m, 1 H), 5.75 (q, J = 7.2 Hz, 1 H), 7.05-7.12 (m, 2 H), 7.27 (t, J = 1.8 Hz, 1 H), 7.70 (d, J = 7.5 Hz, 1 H), 8.07 (br s, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 174.3, 135.6, 133.9, 128.3, 121.3, 119.9, 119.6, 111.0, 110.8, 44.0, 44.0, 31.9, 18.1, 18.0, 13.0. HRMS (EI): m/z calcd for C15H18N2O: 242.1419; found: 242.1420.