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Synlett 2009(5): 793-797  
DOI: 10.1055/s-0028-1087942
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Facile Cross-Metathesis-Radical-Cyclisation Approach to Monobenzannulated Spiroketals

Yen-Cheng (William) Liu, Jonathan Sperry, Dominea C. K. Rathwell, Margaret A. Brimble*
Department of Chemistry, University of Auckland, 23 Symonds St., Auckland 1142, New Zealand
Fax: +64(9)3737422; e-Mail: m.brimble@auckland.ac.nz;
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Publikationsverlauf

Received 24 November 2008
Publikationsdatum:
24. Februar 2009 (online)

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Abstract

The synthesis of a series of 5,5-, 5,6-, and 6,6-mono­benzannulated spiroketals using a novel cross-metathesis-radical-­cyclisation approach is reported. Cross metathesis between two olefin coupling partners resulted in the formation of a heterodimer which upon hydrogenation furnished a saturated alcohol product. Oxidative radical cyclisation then afforded the desired monobenz­annulated spiroketals in good overall yield.

Key words

cross metathesis - radical cyclisation - spiroketal - rubromycins - berkelic acid

21

General Procedure - Oxidative Radical Cyclisation
A mixture of alcohol (0.052 mmol), PhI(OAc)2 (0.106 mmol), and I2 (0.118 mmol) in anhyd cyclohexane (4.3 mL) was degassed with argon at r.t. for 15 min. The resulting solution was cooled in an ice-water bath (7 ˚C) and irradiated with a desk lamp (60 W) for 2-3 h after which it was diluted with Et2O (10 mL), then sat. Na2S2O3 (10 mL) and sat. NaHCO3 (10 mL) were added. After separation of both phases, the aqueous phase was extracted with Et2O (4 × 15 mL). The organic phases were combined, dried over anhyd MgSO4, filtered, and the solvents concentrated in vacuo. The crude product was purified by column chromatography on SiO2 (100% n-pentane, then n-pentane-Et2O, 12:1) to give the spiroketal product.
(±)-4′-Methyl-3′,4′5′,6′tetrahydro-3 H -spiro(benzofuran-2,2′-pyran) (6) Pale yellow oil (7 mg, 0.034 mmol, 42%); R f  = 0.31 (hexanes-Et2O, 10:1). IR (film): 2946, 2925, 2869, 1597, 1479, 1461, 1377, 1238, 1216, 1121, 1096, 1084, 1034, 869, 826, 810, 791, 776, 747, 706 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 0.98 (d, J = 6.6 Hz, 3 H, C-4′-CH 3), 1.33 (qd, J = 12.8, 4.9 Hz, 1 H, Hax-5′), 1.47 (dd, J = 13.1, 12.5 Hz, 1 H, Hax-3′), 1.64 (dtd, J = 13.2, 3.8, 1.9 Hz, 1 H, Heq-5′), 2.03 (ddd, J = 13.4, 3.8, 1.8 Hz, 1 H, Heq-3′), 2.08-2.24 (m, 1 H, Hax-4′), 3.05 (d, J = 16.3 Hz, 1 H, Ha-3), 3.12 (d, J = 16.3 Hz, 1 H, Hb-3), 3.74 (ddd, J = 11.4, 4.9, 1.5 Hz, 1 H, Heq-6′), 4.06 (ddd, J = 11.3, 13.0, 2.4 Hz, 1 H, Hax-6′), 6.80 (d, J = 7.9 Hz, 1 H, H-7), 6.85 (td, J = 7.4, 0.9 Hz, 1 H, H-5), 7.10-7.17 (m, 2 H, H-4 and H-6). ¹³C NMR (75 MHz, CDCl3): δ = 22.1 (CH3, C-4′-CH3), 26.2 (CH, C-4′), 33.3 (CH2, C-5′), 42.5 (CH2, C-3′) 42.8 (CH2, C-3), 62.6 (CH2, C-6′), 109.7 (CH, C-7), 109.8 (C, C-2), 120.6 (CH, C-5), 124.9 (CH, C-4), 126.0 (C, C-3a), 127.9 (CH, C-6), 158.2 (C, C-7a). MS (EI, 70 eV): m/z (%) = 41 (30), 51 (12), 55 (15), 69 (16), 78 (41), 91 (12), 97 (70), 107 (29), 115 (4), 121 (4.5), 131 (21), 134 (10), 145 (3), 159 (2.5), 171 (1.5), 189 (59.5), 203 (5), 204 (100) [M]+. HRMS (EI): m/z [M]+ calcd for C13H16O2: 204.1150; found: 204.1146.
(±)-4′-Methyl-4′,5′-dihydro-3 H ,3′ H -spiro(benzofuran-2,2′-furan) (7a,b) Pale yellow oil (8 mg, 0.042 mmol, 73%); 7a/7b = 1.4:1, mixture of inseparable major (7a) and minor* (7b) diastereomers; R f  = 0.33 (hexanes-EtOAc, 9:1). IR (film): 2954, 2924, 2855, 1598, 1479, 1462, 1377, 1241, 1120, 1082, 1010, 830, 779, 747, 706 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 1.13 (d, J = 6.8 Hz, 3 H, C-4′-CH 3), 1.20 (d, J = 6.6 Hz, 2.1 H, C-4′-CH 3*), 1.73 (dd, J = 12.9, 10.1 Hz, 1 H, HB-3′), 2.12 (dd, J = 13.6, 6.0 Hz, 0.7 H, HA-3′*), 2.38 (dd, J = 13.4, 9.4 Hz, 0.7 H, HB-3′*), 2.45-2.54 (m, 0.7 H, H-4′*), 2.51 (dd, J = 12.9, 7.0 Hz, 1 H, HA-3′), 2.69-2.82 (m, 1 H, H-4′), 3.23-3.32 (m, 3.4 H, H-3 and H-3*), 3.56 (t, J = 8.0 Hz, 1 H, HB-5′), 3.68 (t, J = 8.2 Hz, 0.7 H, HA-5′*), 4.13 (t, J = 7.9 Hz, 0.7 H, HB-5′*), 4.25 (t, J = 8.0 Hz, 1 H, HA-5′), 6.76 (d, J = 8.4 Hz, 1 H, H-7), 6.79 (d, J = 8.9 Hz, 0.7 H, H-7*), 6.85 (t, J = 7.4 Hz, 1.7 H, H-5 and H-5*), 7.11 (t, J = 7.9 Hz, 1.7 H, H-6 and H-6*), 7.16 (d, J = 7.4 Hz, 1.7 H, H-4 and H-4*). ¹³C NMR (100 MHz, CDCl3): δ = 17.7 (CH3, C-4′-CH3), 18.0 (CH3, C-4′-CH3*), 32.3 (CH, C-4′), 32.9 (CH, C-4′*), 39.0 (CH2, C-3), 40.1 (CH2, C-3*), 44.6 (CH2, C-3′*), 45.2 (CH2, C-3′), 75.3 (CH2, C-5′*), 75.5 (CH2, C-5′), 109.4 (CH, C-7), 109.5 (CH, C-7*), 118.6 (C, C-2*), 118.7 (C, C-2), 120.46 (CH, C-5), 120.51 (CH, C-5*), 124.49 (CH, C-4*), 124.53 (CH, C-4), 125.7 (C, C-3a), 125.8 (C, C-3a*), 127.89 (CH, C-6*), 127.94 (CH, C-6), 157.7 (C, C-7a), 158.0 (C, C-7a*). MS (EI, 70 eV): m/z (%) = 37 (21), 47 (41.5), 78 (10), 83 (100), 85 (65.5), 107 (21), 131 (6), 134 (3.5), 175 (9), 190 (30) [M]+. HRMS (EI): m/z [M]+ calcd for C12H14O2: 190.0994; found: 190.0990.