Heteroaryl Radicals: A Furyl Radical in the Synthesis of the Tricyclic ­Framework of Eremophilane Sesquiterpenoids

Abstract

Studies on the intramolecular addition of thieno and ­furan radicals to alkenyl groups are reported. The radicals undergo a 6-endo-trig selective cyclization to alkenyl systems resulting in a linearly annulated tricyclic moiety.

radical reactions - cyclizations - furans - terpenoids

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Radical cyclization of 6 and 12 with Bu ₃ SnH To a solution of 6 or 12 (50 mg, 0.227 mmol or 0.245 mmol) in degassed anhyd benzene (30 mL) heated under reflux were added Bu₃SnH (1.5 equiv) and AIBN (5 mg, 0.02 mmol) in degassed anhyd benzene (20 mL) slowly by syringe pump. The addition of Bu₃SnH was carried out over 2 h and the mixture was heated under reflux for 8 h. The solvent was removed under reduced pressure, Et₂O (20 mL) and a sat. aq solution of KF (20 mL) were added to the residue; the whole mixture was stirred at r.t. for 24 h. The organic phase was separated, washed with brine, dried, and concentrated. Purification was carried out by chromatography(hexane).

<A NAME="RG15205ST-15">15</A>

Spectral data of representative compounds.
5,5-Dimethyl-4,4a,5,6,7,8,8a,9-octahydronaphtho[2,3- b ]thiophene ( 7) ¹H NMR (CDCl₃, 200 MHz): δ = 0.88 (s, 3 H), 0.96 (s, 3 H), 1.25-1.59 (m, 8 H), 2.27-2.41 (m, 2 H), 2.62-2.88 (m, 2 H), 6.73 (d, 1 H, J = 5.11 Hz), 7.02 (d, 1 H, J = 5.11 Hz); MS (EI, 70 ev): m/z = 220 (M⁺); Anal. Calcd for C₁₄H₂₀S: C, 76.30; H, 9.15. Found: C, 76.45; H, 9.25.
8,8-Dimethyl-4,4a,5,6,7,8,8a,9-octahydronaphtho[2,3- b ]furan ( 13) ¹H NMR (CDCl₃, 200 MHz): δ = 0.88 (s, 3 H), 0.96 (s, 3 H), 1.21-1.58 (m, 8 H), 1.71-2.71 (m, 4 H), 6.15 (br s, 1 H), 7.22 (br s, 1 H); ESI-MS: m/z = 205.12 [M + H]⁺; Anal. Calcd for C₁₄H₂₀O: C, 82.30; H, 9.87. Found: C, 82.65; H, 9.76.