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Synlett 2009(18): 2965-2970  
DOI: 10.1055/s-0029-1218275
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Tunable, Regioselective Control of Iodine-Catalyzed Allylic Substitution of Cyclic Baylis-Hillman Adducts with Indoles

Zahid Shafiqa,b, Zhen Qiaoa, Li Liu*a, Qi-Yu Zhenga, Dong Wanga, Yong-Jun Chen*a
a Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, P. R. of China
Fax: +86(10)62554449; e-Mail: lliu@iccas.ac.cn; e-Mail: yjchen@iccas.ac.cn;
b Department of Chemistry, B. Z. University, Multan-60800, Pakistan
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Publication History

Received 3 July 2009
Publication Date:
09 October 2009 (online)

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Abstract

Regioselective control over the nucleophilic substitution of cyclic Baylis-Hillman alcohols with indoles has been developed under the catalysis of molecular iodine. The reaction provided γ-substituted products in THF, whereas the α-products were obtained in TFE via an acid-catalyzed [1,3]-sigmatropic carbon skeleton rearrangement of allylindoles.

Key words

Baylis-Hillman adducts - indoles - molecular iodine - ­regioselectivities - allylic substitution

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13

To a solution of Baylis-Hillman adduct 2a (0.2 mmol) and indole 1a (0.2 mmol) in TFE (or THF) (5 mL), was added iodine (0.02 mmol). The resulting reaction mixture was heated under reflux until completion as judged by TLC, or for the time indicated. After cooling, the reaction mixture was diluted with CH2Cl2 and extracted into sat. Na2S2O3 (3 × 5 mL). The combined organic extract was dried over anhydrous Na2SO4, concentrated in vacuum and purified by column chromatography over silica gel (petroleum ether-EtOAc, 8:1) to afford the desired α-product 3a (or γ-product 4a when THF was used as the solvent).
2-[(2-Methylindolyl)phenylmethyl]cyclopent-2-enone (3a): Off-white solid, mp 135-136 ˚C; IR (KBr): 3393, 2919, 1694, 1456, 1229, 1007, 751 cm-¹; ¹H NMR (CDCl3, 300 MHz): δ = 2.20 (s, 3 H), 2.25-2.62 (m, 4 H), 5.29 (s, 1 H), 6.82-6.87 (m, 1 H), 6.96 (t, J = 7.41 Hz, 1 H), 7.06-7.18 (m, 7 H), 7.23 (s, 1 H), 7.84 (br s, 1 H); ¹³C NMR (CDCl3, 75 MHz): δ = 11.0, 25.3, 33.7, 36.8, 109.3, 110.1, 118.0, 118.1, 119.6, 125.0, 126.8, 127.1, 127.2, 131.4, 134.3, 140.8, 147.5, 158.8, 207.7; EI-MS: m/z (%) = 301, 286, 284, 270, 244, 146, 130 (100); HRMS: m/z calcd. for C21H19NO: 301.1467; found: 301.1466.
(E)-2-Benzylidene-3-(2-methyl-1H-indol-3-yl)cyclopentan-one (4a): Yellow solid; mp 184-185 ˚C; IR (KBr): 3397, 2925, 1704, 1615, 1456, 1223, 1179, 691 cm-¹; ¹H NMR (CDCl3, 300 MHz): δ = 2.13-2.22 (m, 1 H), 2.31 (s, 3 H), 2.35-2.65 (m, 3 H), 4.71 (t, J = 2.53 Hz, 1 H), 7.04-7.46 (m, 9 H), 7.61 (s, 1 H), 7.79 (br s, 1 H); ¹³C NMR (CDCl3, 75 MHz): δ = 12.6, 30.1, 36.7, 37.9, 110.3, 112.4, 118.3, 119,4, 121.1, 127.7, 128.3, 129.2, 130.7, 130.8, 134.3, 134.7, 135.1, 138.7, 208.9; EI-MS: m/z (%) = 301 (100), 286, 272, 258, 244, 168, 130; HRMS: m/z calcd. for C21H19NO: 301.1467; found: 301.1469.