Novel cascade of seven radical-mediated 6-endo-trig cyclisations leading to a unique all-trans, anti heptacycle

Abstract

A cascade of seven radical-mediated 6-endo-trig cyclisations from the all-E-heptaene selenoate ester 1 results in the production of the all-trans, anti heptacycle 2 together with the isolation of the all-trans, anti tetracycle 15.

References

1. See for example (a) L. Chen, G. B. Gill, G. Pattenden and H. Simonian, J. Chem. Soc., Perkin Trans. 1, 1996, 31 Reference 7 below; and extensive bibliography contained in these publications; (b) S. A. Hitchcock, S. J. Houldsworth, G. Pattenden, D. C. Pryde, N. M. Thomson and A. J. Blake, J. Chem. Soc., Perkin Trans. 1, 1998, 3181; (c) G. J. Hollingworth, G. Pattenden and D. J. Schulz, Aust. J. Chem., 1995, 48, 381; (d) S. Handa and G. Pattenden, Chem. Com-mun., 1998, 311; S. Handa and G. Pattenden, Contemp. Org. Synth., 1997, 4, 196.
2. For a similar strategy for the synthesis of the octaprenol 3c see: (a) K. Sato, S. Inoue, A. Onishi, N. Uchida and N. Minowa, J. Chem. Soc., Perkin Trans. 1, 1981, 761; (b) E. E. van Tamelen and S. A. Marson, Bioorg. Chem., 1982, 11, 219.
3. All new compounds displayed satisfactory spectroscopic data together with microanalytical and/or mass spectrometric data.
4. Typical procedure: A solution of tributyltin hydride (8 µl, 8.7 mg, 29.8 µmol) and AIBN (1 mg) in benzene (2 ml) was added dropwise over 8 h to a refluxing solution of the phenyl selenoate 1(16.9 mg, 23.9 µmol) and AIBN (0.5 mg) in dry degassed benzene (6 ml). The mixture was heated under reflux for a further 3 h, then cooled and evaporated to dryness in vacuo. The residue was purified by chromatography on silica gel using diethyl ether–light petroleum (bp 40–60 °C) as eluent and gave the heptacycle 2(2.3 mg, 17%) as colourless crystals, mp 269–271 °C (ethyl acetate–pentane); ν_max(CHCl₃)/cm^–1 3626, 2928, 2853, 1700, 1465, 1387, 1260, 1110 and 1010; δ_H(500 MHZ; CDCl₃) 3.85 (1H, dd, J 4.3 and 10.4 HZ, CHHOH), 3.59 (1H, app. t, J 10.4 HZ, CHHOCH), 2.31–2.27 (2H, m), 2.14–0.74 (complex series of multiplets), 0.95 (3H, d, J 7.6 HZ, CHCH₃), 0.85 (3H, s, CH₃), 0.84 (3H, s, CH₃), 0.81 (6H, s, 2 × CH₃), 0.79 (3H, s, CH₃) and 0.71 (3H, s, CH₃); δ_C(125.8 MHZ; CDCl₃) 213.8 (s), 61.6 (d), 61.5 (d), 61.4 (2 × d), 60.9 (t), 59.7 (d), 59.1 (d), 56.1 (d), 43.4 (s), 42.0 (t), 41.9 (t), 41.8 (t), 41.7 (t), 40.8 (t), 38.7 (t), 38.1 (t), 37.8 (2 × s), 37.7 (s), 37.6 (s), 37.5 (s), 34.5 (t), 28.3 (d), 22.3 (t), 18.2 (t), 18.2 (q), 17.4 (q), 17.3 (q), 17.2 (q), 17.11 (t), 17.07 (2 × t), 17.0 (q), 16.9 (t), 16.2 (t), 15.4 (q) and 13.8 (q); m/z(CI) 533.4704 ((M + H⁺)– H₂O, C₃₈H₆₁O requires 533.4722): and the tetracycle 15(∼25%) as an oil, µ_max(CHCl₃)/cm^–1 2938, 2875, 2852, 1698, 1663, 1451, 1386, 1265 and 1228; δ_H(500 MHZ; CDCl₃) 5.43 (1H, t, J 6.7 HZ, C=CHCH₂OH), 5.13–5.10 (2H, m, 2 × C=CH), 4.16 (2H, d, J 6.7 HZ, CH₂OH), 2.27–0.80 (complex series of multiplets), 1.68 (3H, s, C=C(CH₃)), 1.60 (6H, s, 2 × C=C(CH₃)), 0.91 (3H, d, J 7.1 HZ, CHCH₃), 0.86 (3H, s, CH₃), 0.85 (3H, s, CH₃), 0.84 (3H, s, CH₃); δ_C(125.8 MHZ; CDCl₃) 213.8 (s), 139.8 (s), 135.4 (s), 135.0 (s), 124.2 (d), 123.7 (d), 123.3 (d), 65.8 (t), 61.4 (d), 61.1 (d), 59.7 (d), 51.9 (d), 43.4 (s), 42.0 (t), 41.8 (t), 40.8 (t), 39.7 (t), 39.5 (t), 38.1 (t), 38.0 (t), 37.7 (t), 37.5 (s), 37.4 (s), 30.3 (d), 26.6 (t), 26.3 (t), 22.3 (t), 21.4 (t), 17.3 (2 × q), 17.1 (3 × t), 16.3 (q), 16.0 (q), 15.9 (q), 15.3 (q) and 13.8 (q); m/z(EI) 532.4669 (M⁺- H₂O, C₃₈H₆₀O requires 532.4644).
5. D. S. de Miranda, G. Brendolan, P. M. Imamura, M. González Sierra, A. J. Marsaioli and E. A. Rúveda, J. Org. Chem., 1981, 46, 4851.
6. H. Beierbeck, J. K. Saunders and J. W. Apsimon, Can. J. Chem., 1977, 55, 2813; H. Beierbeck and J. K. Saunders, Can. J. Chem., 1975, 53, 1307.
7. For a similar ¹³C NMR based analysis of the stereochemistry of fused cyclohexane systems see: A. Batsanov, L. Chen, G. B. Gill and G. Pattenden, J. Chem. Soc., Perkin Trans. 1, 1996, 45.
8. For some novel polycyclisations using the Heck reaction leading to penta- and heptacycles see: T. Sighihara, C. Coperet, Z. Owczarczyk, L. S. Harding and E. Negishi, J. Am. Chem. Soc., 1994, 116, 7923; B. M. Trost and Y. Shi, J. Am. Chem. Soc., 1993, 115, 9421.