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

doi:10.1055/s-2007-984506

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Synlett 2007(11): 1725-1729
DOI: 10.1055/s-2007-984506

LETTER

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;

Further Information

Publication History

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

Abstract
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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

References and Notes

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2

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

10

Schmidt, D.; Beifuss, U., unpublished results.

17

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): λ_max (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′-H_A), 1.80-1.84 (m, 1 H, 4′-H_A), 1.86-1.90 (m, 1 H, 5′-H_B), 2.09-2.12 (m, 1 H, 4′-H_B), 2.36 (dd, 1 H, ² J ₁ _′ _-HA,1 _′ _-HB = 16.9 Hz, ³ J ₁ _′ _-HA,2 _′ _-H = 13.0 Hz, 1′-H_A), 2.62 (dd, 1 H, ² J ₁ _′ _-HB,1 _′ _-HA = 17.3 Hz, ³ J ₁ _′ _-HB,2 _′ _-H = 4.6 Hz, 1′-H_B), 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): λ_max (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′-H_B), 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′-H_A, 5′-H_B), 2.13-2.17 (m, 1 H, 5′-H_A), 2.34 (dd, 1 H, ² J ₁ _′ _-HA,1 _′ _-HB = 16.4 Hz, ³ J ₁ _′ _-HB,2 _′ _-H = 12.8 Hz, 1′-H_A), 2.71 (dd, 1 H, ² J ₁ _′ _-HB,1 _′ _-HA = 16.4 Hz, ³ J ₁ _′ _-HB,2 _′ _-H = 4.9 Hz, 1′-H_B), 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.

20

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