Total Syntheses of Spirooliganones A and B

Abstract

This paper describes the total syntheses of spirooliganones A and B, which provides control over the stereochemistry of the spiro center via a cascade reaction involving the in situ formation of an o-quinone methide and a hetero-Diels–Alder reaction.

Key words

total synthesis - spirooliganones A and B - spiro center - hetero-Diels–Alder reaction - {¹⁹F}-¹H HOESY

• References and Notes

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• 10 Potassium triethylborohydride (0.194 mL, 1.0 M THF solution, 0.194 mmol) was added to a solution of 9 (50.0 mg, 0.129 mmol) in THF/HMPA (5:1, 2 mL) at –78 °C. After 15 min of stirring at –78 °C, saturated aqueous NH₄Cl was added to the reaction mixture, and the mixture was extracted with EtOAc (3×). The combined organic extracts were dried (MgSO₄) and concentrated in vacuo. The residue was purified by PTLC (hexane/EtOAc = 7:1) to afford 8 (22.5 mg, 47%) as a white solid and 16 (5.3 mg, 11%) as a white solid.Compound 8: R_f = 0.63 (hexane/EtOAc = 7:1); [α]_D ²³ –29 (c 1.2, CHCl₃). IR (neat): 2944, 1685, 1123, 881 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.07–1.14 (m, 21 H), 1.35 (s, 3 H), 1.37 (s, 3 H), 2.15 (dd, J = 13.5, 4.3 Hz, 1 H), 2.72 (dd, J = 13.5, 5.5 Hz, 1 H), 4.40 (t, J = 4.8 Hz, 1 H), 5.85 (dd, J = 13.3, 1.6 Hz, 1 H), 6.03 (d, J = 9.8 Hz, 1 H), 6.97 (t, J = 10.3 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 10.2, 15.96, 15.99, 21.7, 25.4, 41.0, 74.2 (d, J _CF = 23.1 Hz), 77.0, 85.2, 106.8 (d, J _CF = 11.6 Hz), 123.3, 146.0 (d, J _CF = 4.8 Hz), 172.6 (d, J _CF = 290.9 Hz), 185.2 (d, J _CF = 16.4 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –98.4. HRMS (ESI): m/z calcd for C₂₀H₃₄O₃FSi [M + H]⁺: 369.2256; found: 369.2242.Compound 16: R_f = 0.57 (hexane/EtOAc = 7:1). [α]_D ²³ –9.3 (c 0.57, CHCl₃). IR (neat): 2944, 1683, 1139, 883 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.07–1.12 (m, 21 H), 1.30 (d, J = 0.9 Hz, 3 H), 1.40 (s, 3 H), 2.26 (dd, J = 12.9, 7.0 Hz, 1 H), 2.58 (dd, J = 12.6, 9.6 Hz, 1 H), 4.38 (dd, J = 9.5, 6.7 Hz, 1 H), 5.87 (dd, J = 13.0, 1.6 Hz, 1 H), 6.03 (dt, J = 9.8, 1.3 Hz, 1 H), 6.62 (t, J = 10.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 12.2, 17.9, 18.0, 22.4 (d, J _CF = 2.9 Hz), 28.4, 41.2, 74.3 (d, J _CF = 24.1 Hz), 78.2, 85.2, 109.3 (d, J _CF = 11.6 Hz), 125.5, 146.7 (d, J _CF = 4.8 Hz), 174.0 (d, J _CF = 291.9 Hz), 187.1 (d, J _CF = 15.4 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ = –96.6. HRMS (ESI): m/z calcd for C₂₀H₃₄O₃FSi [M + H]⁺: 369.2256; found: 369.2247.
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