Synthesis of the A-Ring of Goniodomin A via Radical Cyclization with Vinyl Sulfoxide

Abstract

A short synthesis of the A-Ring of Goniodomin A was developed via radical cyclization using vinyl sulfoxide. We found that optically inactive sulfoxides are applicable to the cyclization and Pummerer rearrangement with high stereoselectivity.

Key words

radical cyclization - Pummerer rearrangement - cyclic ether - goniodomin A

• References and Notes

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• 13 Synthesis of 10a: Tributyltin hydride (2.76 mL, 10.2 mmol) was added to a solution of 7 (1.95 g, 5.10 mmol) and AIBN (419 mg, 2.55 mmol) in toluene (170 mL) at r.t. After stirring for 2 h at 90 °C, the solution was cooled to r.t. and concentrated in vacuo. The residue was purified by flash column chromatography (SiO₂; n-hexane/EtOAc = 4:1) to give vinyl stannane 10a (2.38 g, 3.53 mmol, 69% yield) as a colorless oil and vinyl ether 11 (124 mg, 510 μmol, 10% yield) as a colorless oil. 10a: [α]_D ²³ –79.0 (c 1.1, CHCl₃). IR (neat): 3036, 2953, 2922, 2870, 2852, 1606, 1101, 1045 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.58 (d, J = 7.8 Hz, 2 H), 7.53–7.48 (m, 2 H), 7.41–7.35 (m, 5 H), 5.79 (s, 0.4 H), 5.61 (s, 0.6 H), 5.55 (s, 0.6 H), 5.52 (s, 0.4 H), 4.50 (d, J = 10.1 Hz, 0.6 H), 4.42 (d, J = 5.1 Hz, 0.6 H), 4.24 (dd, J = 11.4, 4.1 Hz, 0.4 H), 3.78–3.65 (m, 2 H), 3.60–3.48 (m, 1.4 H), 3.34 (ddd, J = 9.7, 9.7, 4.6 Hz, 0.4 H), 3.19 (d, J = 12.9 Hz, 0.6 H), 3.11 (dd, J = 13.3, 3.2 Hz, 0.4 H), 2.88 (t, J = 12.4 Hz, 0.6 H), 2.69–2.56 (m, 1.6 H), 2.44–2.37 (m, 3.4 H), 1.55–1.37 (m, 6 H), 1.35–1.23 (m, 6 H), 0.94–0.85 (m, 15 H). ¹³C NMR (100 MHz, CDCl₃): δ = 149.7, 141.7, 141.6, 137.4, 130.2, 129.3, 128.5, 126.3, 126.24, 126.16, 125.8, 124.6, 124.0, 102.0, 101.9, 79.6, 79.2, 77.3, 75.6, 74.5, 73.8, 73.6, 69.4, 69.2, 61.6, 59.8, 41.5, 41.2, 29.3, 29.2, 29.1, 27.6, 27.4, 27.1, 21.63, 21.56, 13.8, 10.4. HRMS: m/z [M + Na]⁺ calcd for C₃₄H₅₀O₄NaSSn: 697.2344; found: 697.2351.
• 14 Synthesis of 17 from 12: 2,6-Lutidine (605 μL, 5.20 mmol) and TFAA (735 μL, 5.20 mmol) were added to a solution of 12 (1.00 g, 2.60 mmol) in CH₂Cl₂ (26.0 mL) at 0 °C. After stirring for 30 min at that temperature, MeOH (26.0 mL) and NaBH₄ (984 mg, 26.0 mmol) were added. After stirring for 3 h, NaBH₄ (984 mg, 26.0 mmol) was additionally added. The solution was diluted with CH₂Cl₂, and the organic layer was washed with brine. The solution was dried over MgSO₄ and concentrated in vacuo. The residue was purified by flash column chromatography (SiO₂; n-hexane/EtOAc = 2:1) to give methylene alcohol 17 (557 mg, 2.13 mmol, 82% yield) as a white solid. 17: mp 118–120 °C; [α]_D ²⁶ –36.3 (c 1.0, CHCl₃). IR (neat): 3291, 2964, 2870, 1645, 1382, 1329, 1101, 908 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.52–7.48 (m, 2 H), 7.40–7.34 (m, 3 H), 5.56 (s, 1 H), 5.02 (s, 1 H), 4.87 (s, 1 H), 4.35 (dd, J = 10.5, 4.6 Hz, 1 H), 4.04–4.01 (m, 1 H), 3.96 (dd, J = 11.5, 3.2 Hz, 1 H), 3.84 (dd, J = 11.5, 7.3 Hz, 1 H), 3.73 (dd, J = 10.5, 10.5 Hz, 1 H), 3.64–3.54 (m, 2 H), 2.77 (dd, J = 12.9, 4.6 Hz, 1 H), 2.48 (br dd, J = 11.5, 11.5 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 140.6, 137.3, 129.1, 128.4 (2C), 126.1 (2C), 111.4, 101.6, 78.6, 78.4, 73.2, 69.2, 62.5, 38.8. HRMS: m/z [M + Na]⁺ calcd for C₁₅H₁₈O₄Na: 285.1097; found: 285.1088.