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Synlett 2007(11): 1725-1729  
DOI: 10.1055/s-2007-984506
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient Lewis Acid Mediated Epoxyolefin Cyclizations with Pyrones as Terminators in Liquid SO2 as a Solvent

Dietmar Schmidt, Heiko Leutbecher, Jürgen Conrad, Iris Klaiber, Sabine Mika, Gerhard Greiner, Uwe Beifuss*
Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany
Fax: +49(711)45922951; e-Mail: ubeifuss@uni-hohenheim.de;
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Publication History

Received 23 March 2007
Publication Date:
25 June 2007 (online)

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Abstract

Lewis acids like BF3·OEt2, TiCl4, ZnCl2·OEt2, ZnI2, and InCl3 in liquid SO2 as a solvent at low temperatures have been found to be highly efficient in epoxyolefin cyclizations with pyrones as terminators.

Key words

epoxides - Lewis acids - cyclizations - heterocycles - ­pyrones - sulfur dioxide

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Compounds 1 refer to enantiomers and compounds 2-16 to racemates.

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Schmidt, D.; Beifuss, U., unpublished results.

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Cyclization of 6 with BF 3 ·OEt 2 in SO 2 (l)
Compound 6 (200 mg) was dissolved in liquid SO2 (10 mL) at -40 °C and BF3·OEt2 (223 µL, 1.107 mmol) was added dropwise at the same temperature. The resulting dark yellow solution was stirred for 2 h and the reaction mixture was allowed to warm to -20 °C. The cooling bath was removed and the excess SO2 was evaporated by stirring at r.t. The residue was treated with Et3N (780 µL, 5.56 mmol) followed by MeOH (2 mL) and CH2Cl2 (20 mL). After stirring for 10 min the volatiles were removed in vacuo. When the residue was submitted to flash column chromatography (SiO2, EtOAc) two fractions were isolated: 63 mg crude 7 and 126 mg crude 8; the total yield of 7 and 8 amounted to 95%. Analytically pure samples of 7 and 8 were obtained by semipreparative HPLC.

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Selected Data for 7
IR (ATR): 3251, 2946, 2410, 1716, 1642, 1578, 1480, 1400, 1390, 1220, 1182, 1126, 1024, 976, 926, 850, 802, 744, 695 cm-1. UV/Vis (MeCN-H2O, 1:3): λmax (log ε) = 236.0 (4.27), 331.0 nm (3.94). 1H NMR (500 MHz, CD3OD): δ = 0.94 (s, 3 H, 9′-H3), 1.16 (s, 3 H, 8′-H3), 1.36 (s, 3 H, 10′-H3), 1.68 (dd, 1 H, 3 J 2 ′ -H,1 ′ -HB = 13.0 Hz, 3 J 2 ′ -H,1 ′ -HB = 4.6 Hz, 2′-H), 1.71-1.74 (m, 1 H, 5′-HA), 1.80-1.84 (m, 1 H, 4′-HA), 1.86-1.90 (m, 1 H, 5′-HB), 2.09-2.12 (m, 1 H, 4′-HB), 2.36 (dd, 1 H, 2 J 1 ′ -HA,1 ′ -HB = 16.9 Hz, 3 J 1 ′ -HA,2 ′ -H = 13.0 Hz, 1′-HA), 2.62 (dd, 1 H, 2 J 1 ′ -HB,1 ′ -HA = 17.3 Hz, 3 J 1 ′ -HB,2 ′ -H = 4.6 Hz, 1′-HB), 3.41 (dd, 1 H, 3 J 6 ′ -H,5 ′ -HA = 11.6 Hz, 3 J 6 ′ -H,5 ′ -HB = 4.4 Hz, 6-H), 6.89 (s, 1 H, 5-H), 7.73 (dd, 1 H, 3 J 5 ′′ -H,6 ′′ -H = 7.9 Hz, 3 J 5 ′′ -H,4 ′′ -H = 5.1 Hz, 5′′-H), 8.46 (d, 1 H, 3 J 6 ′′ -H,5 ′′ -H = 8.1 Hz, 6′′-H). 8.74 (br s, 1 H, 4′′-H), 9.13 (br s, 1 H, 2′′-H). 13C NMR (125 MHz, CD3OD): δ = 15.04 (C-9′), 18.88 (C-1′), 20.14 (C-10′), 27.89 (C-8′), 28.78 (C-5′), 38.27 (C-4′), 39.69 (C-7′), 47.66 (C-2′), 78.10 (C-6′), 82.00 (C-3′), 101.27 (C-5), 101.59 (C-3), 125.43 (C-5′′), 129.28 (C-1′′), 134.70 (C-6′′), 147.19 (C-2′′), 151.68 (C-4′′), 156.70 (C-6), 165.06 (C-4), 165.78 (C-2). MS (EI, 70 eV): m/z (%) = 341 (38) [M+], 323 (4), 308 (9), 256 (11), 202 (100), 148 (26), 121 (47), 106 (59), 78 (42), 43 (41). HRMS (EI, 70 eV): m/z calcd for C20H23NO4: 341.1627; found: 341.1650.

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Selected Data for 8
IR (ATR): 3373, 3076, 2943, 2871, 1647, 1561, 1435, 1260, 1164, 1179, 1127, 1026, 931, 812, 702 cm-1. UV/Vis (MeCN-H2O, 1:3): λmax (log ε) = 228 (4.19), 277 nm (3.99). 1H NMR (500 MHz, CD3OD): δ = 0.94 (s, 3 H, 9′-H3), 1.17 (s, 3 H, 8′-H3), 1.44 (s, 3 H, 10′-H3), 1.70-1.73 (m, 1 H, 4′-HB), 1.76 (dd, 1 H, 3 J 2 ′ -H,1 ′ -HA = 12.6 Hz, 3 J 2 ′ -H,1 ′ -HB = 4.8 Hz, 2′-H), 1.88-1.96 (m, 2 H, 4′-HA, 5′-HB), 2.13-2.17 (m, 1 H, 5′-HA), 2.34 (dd, 1 H, 2 J 1 ′ -HA,1 ′ -HB = 16.4 Hz, 3 J 1 ′ -HB,2 ′ -H = 12.8 Hz, 1′-HA), 2.71 (dd, 1 H, 2 J 1 ′ -HB,1 ′ -HA = 16.4 Hz, 3 J 1 ′ -HB,2 ′ -H = 4.9 Hz, 1′-HB), 3.43 (dd, 1 H, 3 J 6 ′ -H,5 ′ -HA = 11.7 Hz, 3 J 6 ′ -H,5 ′ -HB = 4.1 Hz, 6′-H), 6.92 (s, 1 H, 5-H), 7.71 (dd, 1 H, 3 J 5 ′′ -H,6 ′′ -H = 8.1 Hz, 3 J 5 ′′ -H,4 ′′ -H = 5.0 Hz, 5′′-H), 8.41 (ddd, 1 H, 3 J 6 ′′ -H,5 ′′ -H = 8.2 Hz, 4 J 6 ′′ -H,2 ′′ -H = 2.1 Hz, 4 J 6 ′′ -H,4 ′′ -H = 1.5 Hz, 6′′-H), 8.76 (d, 1 H, 3 J 4 ′′ -H,5 ′′ -H = 4.3 Hz, 4′′-H), 9.09 (br s, 1 H, 2′′-H). 13C NMR (125 MHz, CD3OD): δ = 15.04 (C-9′), 17.32 (C-1′), 20.09 (C-10′), 27.96 (C-8′), 28.78 (C-5′), 38.02 (C-4′), 39.77 (C-7′), 47.95 (C-2′), 78.00 (C-6′), 86.22 (C-3′), 101.19 (C-3), 110.49 (C-5), 125.53 (C-5′′), 128.74 (C-1′′), 135.15 (C-6′′), 147.44 (C-2′′), 152.37 (C-4′′), 158.62 (C-6), 165.12 (C-2), 182.04 (C-4). MS (EI, 70 eV): m/z (%) = 341 (32) [M+], 323 (9), 308 (16), 256 (13), 202 (100), 148 (31), 121 (51), 106 (46), 78 (22), 43 (31). HRMS (EI, 70 eV): m/z calcd for C20H23NO4: 341.1627; found: 341.1622.

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Ab initio calculations were performed at the DFT/B3LYP/6-31G level using a GAUSSIAN 03 package.