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Synlett 2006(8): 1240-1244  
DOI: 10.1055/s-2006-932472
LETTER
© Georg Thieme Verlag Stuttgart · New York

Diastereoselective Tandem Michael Additions of Indoles to 3-Nitrocoumarin Derivatives and Methyl Vinyl Ketone

Meng-Chun Yea, Yao-Yu Yangb, Yong Tang*a, Xiu-Li Suna, Zhi Maa, Wei-Min Qinb
a State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P. R. of China
b College of Chemistry and Chemical Engineering, Donghua University, 1882 West Yan’an Road, Shanghai 200051, P. R. of China
Fax: +86(21)54925078; e-Mail: tangy@mail.sioc.ac.cn;
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Publication History

Received 9 November 2005
Publication Date:
10 March 2006 (online)

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Abstract

Tandem Michael additions of indole derivatives to 3-nitrocoumarins 2, followed by MVK, in one pot, has been developed for the synthesis of multi-functionalized 3,4-dihydrocoumarins bearing a quaternary stereocenter. The reaction proceeds with high diastereoselectivities in good to excellent yields.

Key words

α,β-unsaturated nitroesters - tandem Michael additions - one-pot reactions - 3,4-dihydrocoumarins

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10

Typical Procedure: To a stirred solution of Mg(OTf)2 (0.01 mmol) and 3-nitrocoumarin 2 (0.50 mmol) in i-PrOH (3 mL) at 20 °C in air was added indole derivative 1 (0.51 mmol). After the reaction was complete (ca. 3-12 h, monitored by TLC), MVK (124 µL, 1.50 mmol) and Ph3P (26.2 mg, 0.10 mmol) were added in turn, then DME (3 mL) was added in ca. five minutes. The resulting mixture was stirred for the required time (TLC), concentrated, and purified by flash chromatography on silica gel (PE-EtOAc, 2:1) to give the product 4.
Selected spectral data:
4a: IR (neat): 3418, 1773, 1710, 1554, 1458, 1356, 1226, 1169, 747 cm-1. 1H NMR (300 MHz, CDCl3): δ = 8.43 (br s, 1 H), 7.40-7.33 (m, 3 H), 7.25-7.20 (m, 2 H), 7.14-7.07 (m, 4 H), 4.98 (s, 1 H), 2.86-2.73 (m, 2 H), 2.66-2.44 (m, 2 H), 2.09 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 205.75, 161.25, 149.76, 135.81, 129.64, 128.56, 126.70, 125.60, 124.70, 122.83, 122.60, 120.41, 117.88, 116.78, 111.72, 107.69, 92.98, 43.96, 38.12, 29.87, 28.42. LRMS-EI: m/z (%) = 378 (M+), 274 (100). Anal. Calcd for C21H18N2O5: C, 66.66; H, 4.79; N, 7.40. Found: C, 66.67; H, 4.84; N, 7.40.
4b: IR (neat): 3052, 2926, 1774, 1718, 1554, 1487, 1456, 1338, 1226, 1166, 742 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.38-7.32 (m, 3 H), 7.28-7.20 (m, 2 H), 7.13-7.07 (m, 3 H), 6.97 (s, 1 H), 4.97 (s, 1 H), 3.78 (s, 3 H), 2.80-2.71 (m, 2 H), 2.60-2.44 (m, 2 H), 2.08 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 205.62, 161.22, 149.75, 136.66, 129.56, 128.99, 128.52, 127.41, 125.54, 122.90, 122.37, 120.00, 117.89, 116.75, 109.78, 105.91, 93.04, 43.81, 38.11, 33.07, 29.83, 28.40. LRMS-ESI: m/z = 393 (M + H+). HRMS: m/z calcd for C22H20N2O5Na (M + Na+): 415.1270; found: 415.1267.
4c: IR (neat): 3418, 1770, 1716, 1587, 1556, 1509, 1455, 1360, 1264, 1237, 1169, 1091, 735 cm-1. 1H NMR (300 MHz, DMSO-d 6): δ = 11.27 (s, 1 H), 7.41-7.30 (m, 3 H), 7.05-6.94 (m, 3 H), 6.73-6.61 (m, 2 H), 5.44 (s, 1 H), 3.52 (s, 3 H), 3.00-2.49 (m, 4 H), 2.05 (s, 3 H). 13C NMR (75 MHz, DMSO-d 6): δ = 206.94, 161.87, 150.40, 137.42, 136.24, 130.01, 129.87, 125.64, 121.95, 121.13, 119.26, 119.20, 116.90, 111.76, 103.26, 92.88, 44.23, 38.33, 30.34, 28.41, 12.27. LRMS-ESI: m/z = 393 (M + H+). HRMS: m/z calcd for C22H20N2O5Na (M + Na+): 415.1270; found: 415.1265.
4d: IR (neat): 3421, 1767, 1716, 1554, 1509, 1361, 1264, 1092, 736 cm-1. 1H NMR (300 MHz, CDCl3): δ = 8.50 (br s, 1 H), 7.34-7.30 (m, 1 H), 7.20-7.05 (m, 4 H), 6.98 (d, J = 8.4 Hz, 1 H), 6.87 (d, J = 1.8 Hz, 1 H), 6.53 (d, J = 8.1 Hz, 1 H), 5.86 (br s, 1 H), 3.88 (br s, 3 H), 2.94-2.48 (m, 4 H), 2.08 (s, 3 H). 13C NMR (75 MHz, acetone-d 6): δ = 205.15, 161.57, 154.03, 149.97, 137.47, 128.96, 128.48, 125.23, 124.71, 123.42, 122.72, 117.42, 116.20, 107.21, 105.25, 99.92, 94.32, 54.42, 42.54, 37.47, 28.85, 27.69. LRMS-ESI: m/z = 409 (M + H+). HRMS: m/z calcd for C22H20N2O5Na (M + Na+): 431.1219; found: 431.1217.
Spectral data for compound 3: 1H NMR (300 MHz, CDCl3): δ = 8.27 (br s, 1 H), 7.46-7.04 (m, 9 H), 5.84 (d, J = 9.3 Hz, 1 H), 5.40 (d, J = 9.3 Hz, 1 H).