Cascade radical cyclisations involving enamide double bonds. A synthetic approach to azasteroids

Abstract

Treatment of the enamide selenoesters 8 and 14 with Bu₃SnH–AIBN is shown to lead to the nitrogen tricycle 9 (63%) and the D-homo-12-azasteroid 16 (45%) respectively, by way of serial stereoselective 6-endo-trig radical cyclisations.

References

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9. All new compounds showed satisfactory spectroscopic data, together with microanalytical and/or mass spectrometry data. Data for 9: δ_H(500 MHz, CDCl₃; J/Hz) 3.73 (1H, dd, J 13.9 and 8.3, CHHN), 3.43 (1H, dd, J 13.9 and 7.1, CHHN), 3.37 (1H, app. td, J 10.7 and 2.8, CHN), 2.51 (1H, app. t, J 7.7, COCH), 2.48–2.30 (2H, m, CH₂CO), 2.14 (3H, s, NCOCH₃), 2.10 (1H, m), 1.97 (1H, m), 1.91–1.73 (4H, m), 1.56–1.38 (5H, m), 1.32 (1H, m), 1.12 (1H, m), 0.71 (3H, s, CCH₃); δ_c(125.8 MHz, CDCl₃) 209.8 (s), 171.9 (s), 57.4 (d), 57.1 (d), 52.0 (d), 40.7 (s), 40.4 (t), 40.1 (t), 36.0 (t), 31.7 (t), 26.4 (t), 26.1 (t), 25.6 (t), 23.6 (q), 22.3 (t), 13.0 (q); v_max(liquid film)/cm^–1 2934 (s), 2359 (s), 1714 (s), 1634 (s), 1454 (s), 1200 (s), 1049 (m), 668 (s); m/z(EI) 263.1883 (M⁺; C₁₆H₂₅NO₂ requires M, 263.1885). Data for 16: δ_H(360 MH_z, CDCl₃) 3.55 (2H, m, CHCH₂N), 3.32 (1H, dd, J 10.6 and 2.6, NCHCH₂), 2.32 (3H, m), 2.11 (3H, s, NCOCH₃), 2.15–0.97 (18H, m), 0.85 (3H, s, CCH₃), 0.83 (3H, s, CCH₃); δ_C(90.6 MHz, CDCl₃) 212.2 (s), 171.8 (s), 59.4 (d), 57.9 (d, br), 55.8 (d), 55.0 (d), 43.0 (s), 41.7 (t, br), 40.8 (t), 37.6 (t), 36.3 (t), 33.9 (s), 33.6 (t), 26.6 (t), 25.4 (t), 25.3 (t), 23.0 (q), 22.1 (t), 17.1 (t), 14.7 (q), 13.4 (q); m/z(EI) 331.2500 (M⁺; C₂₁H₃₃NO₂ requires M, 331.2511).
10. In a typical procedure, a solution of Bu₃SnH (60 mg, 0.21 mmol) and AIBN (7 mg) in degassed benzene (2 cm³) was added dropwise over 2 h to a refluxing solution of 8(70 mg, 0.17 mmol) and AIBN (8 mg) in degassed benzene (38 cm³) under argon, and the solution was then heated under reflux for a further 2 h. The solution was evaporated to dryness in vacuo, and the residue was then purified by chromatography on silica using EtOAc–light petroleum (bp 40–60 °C)(1∶3) as eluent to give the tricycle 9(30 mg, 65%) as a colourless oil.
11. C₁₆H₂₅NO₂, M= 263.37. Triclinic, a= 5.884(2), b= 9.265(3), c= 13.687(6)Å, a= 77.23(3), β= 83.17(4), γ= 76.63(3)°, V= 706.2(5)ų, T= 150(2) K, space group P1̄(No. 2), Z= 2, D_x= 1.239 g cm^–3, µ(Mo-Kα)= 0.080 mm^–1. Structure solution and refinement employed all 2464 unique reflections. Final R₁[2071 F≥ 4σ(F)]= 0.0438, wR₂[F², all data]= 0.106, S[F²]= 1.15 for 174 refined parameters. Full crystallographic details, excluding structure factor tables, have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details of the deposition scheme, see ‘Instructions for Authors’, J. Chem. Soc., Perkin Trans. 1, available via the RSC Web page (http://www.rsc.org/authors). Any request to the CCDC for this material should quote the full literature citation and the reference number 207/223.
12. E. Nakamura, S. Aoki, K. Sekiya, H. Oshino and I. Kuwajima, J. Am. Chem. Soc., 1987, 109, 8056.