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DOI: 10.1055/s-2007-1000834
A Short Enantioselective Total Synthesis of (-)-Linderol A
Publication History
Publication Date:
11 December 2007 (online)
Abstract
An efficient short enantioselective total synthesis of (-)-linderol A was achieved via a five-step reaction with 30% overall yield, starting from 4-methoxyphloroacetophenone.
Key words
total synthesis - stereoselectivity - terpenylation - epoxides - hexahydrodibenzofuran
- 1
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References and Notes
Selected Physical Properties for 5[α]D +14 (c 0.44, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 6.56 (s, 1 H, Har), 5.09 (s, 1 H, H2), 3.80 (m, 4 H, H3 and CH3O), 2.40 (s, 3 H, CH3), 2.31 (s, 3 H, CH3), 2.12 (s, 3 H, CH3), 2.03 (m, 2 H), 1.90 (m, 1 H), 1.78 (dt, 1 H, J = 2.3 Hz), 1.63 (s, 3 H, CH3), 1.36 (m, 2 H), 0.86 (d, 3 H, J = 6.8 Hz, CH3), 0.77 (d, 3 H, J = 6.8 Hz, CH3) ppm. 13C NMR (300 MHz, CDCl3): δ = 198.4 (C=O), 169.2 (C=O), 168.5 (C=O), 160.1 (Cq), 147.4 (Cq), 147.1 (Cq), 132.9 (Cq, C1), 124.9 (CH, C2), 124.3 (Cq), 102.6 (CHar), 55.9 (CH3O), 42.5 (CH), 36.0 (CH, C3), 30.8 (CH3), 30.6 (CH2), 28.0 (CH, C4), 23.4 (CH3), 22.3 (CH2), 21.5 (CH3), 21.1 (CH3), 20.8 (CH3), 15.9 (CH3) ppm. LRMS (EI): m/z (%) = 402 (0.1) [M+], 359(52), 317(99), 290(22), 248(100), 233(30). HRMS (EI): m/z calcd for C23H30O6: 402.2042; found: 402.2041.
8Experimental Procedure for 6The mixture of epoxides 2 and 2′ (52.8 mg, 0.126 mmol with a ratio of 2.6:1) was treated at r.t. with 2 mL of a 2% NaOH solution in MeOH-H2O (1:1). The solution was stirred at r.t. for 1 h, then neutralized with 10% HCl. The mixture was extracted with CH2Cl2, the organic layer was washed with H2O and dried over MgSO4. The solvent was then removed under reduced pressure and the residue was purified by silica gel column chromatography (CH2Cl2-EtOAc, 90:10) to give 6 as a pale yellow solid (29 mg, 0.087 mmol, 69% or 87% from 2); mp 146-147 °C. IR (KBr): 3430, 2947, 2921, 1625, 1433, 1363, 1293, 1211, 1150, 1054, 831, 805 cm-1. 1H NMR (300 MHz, CDCl3): δ = 13.16 (s, 1 H, OH), 6.02 (s, 1 H, H2), 4.16 (dd, 1 H, J = 5.5, J = 1.0 Hz, H5a), 3.81 (s, 3 H, CH3O), 3.11 (dd, 1 H, J = 11.1, 5.5 Hz, H9a), 2.60 (s, 3 H, CH3), 1.80 (m, 3 H, H7 and CH i -Pr), 1.61 (s, 1 H, OH), 1.50 (s, 3 H, CH3), 1.40 (m, 2 H, H8), 1.10 (m, 1 H, H9), 0.90 (d, 3 H, J = 6.9 Hz, CH3), 0.83 (d, 3 H, J = 6.9 Hz, CH3) ppm. 13C NMR (300 MHz, CDCl3): δ = 201.8 (C=O), 165.0 (C3), 162.0 (Cqar), 161.8 (Cqar), 113.1 (C9b), 102.9 (C4), 92.5 (C2), 92.3 (C5a), 69.3 (CH, C6), 55.4 (CH3O), 46.5 (CH, C9), 39.6 (C9a), 35.2 (CH2, C7), 31.1 (CH3C=O), 28.2 (CH3), 27.1 (CH i -Pr), 21.7 (CH3), 17.1 (C8), 15.3 (CH3). LRMS (EI): m/z (%) = 334 (50) [M+], 318 (40), 249 (98), 233 (100), 207 (48), 195 (22). HRMS (EI): m/z calcd for C19H26O5: 334.1780; found: 334.1788.