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

Yen-Cheng (William) Liu; Jonathan Sperry; Dominea C. K. Rathwell; Margaret A. Brimble

doi:10.1055/s-0028-1087942

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Synlett 2009(5): 793-797
DOI: 10.1055/s-0028-1087942

LETTER

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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Publication History

Received 24 November 2008
Publication Date:
24 February 2009 (online)

Abstract
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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

References and Notes

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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, H_ax-5′), 1.47 (dd, J = 13.1, 12.5 Hz, 1 H, H_ax-3′), 1.64 (dtd, J = 13.2, 3.8, 1.9 Hz, 1 H, H_eq-5′), 2.03 (ddd, J = 13.4, 3.8, 1.8 Hz, 1 H, H_eq-3′), 2.08-2.24 (m, 1 H, H_ax-4′), 3.05 (d, J = 16.3 Hz, 1 H, H_a-3), 3.12 (d, J = 16.3 Hz, 1 H, H_b-3), 3.74 (ddd, J = 11.4, 4.9, 1.5 Hz, 1 H, H_eq-6′), 4.06 (ddd, J = 11.3, 13.0, 2.4 Hz, 1 H, H_ax-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, H_B-3′), 2.12 (dd, J = 13.6, 6.0 Hz, 0.7 H, H_A-3′*), 2.38 (dd, J = 13.4, 9.4 Hz, 0.7 H, H_B-3′*), 2.45-2.54 (m, 0.7 H, H-4′*), 2.51 (dd, J = 12.9, 7.0 Hz, 1 H, H_A-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, H_B-5′), 3.68 (t, J = 8.2 Hz, 0.7 H, H_A-5′*), 4.13 (t, J = 7.9 Hz, 0.7 H, H_B-5′*), 4.25 (t, J = 8.0 Hz, 1 H, H_A-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.