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DOI: 10.1055/s-2004-815417
Transition Metal Complexes in Organic Synthesis, Part 71: [1] First Total Synthesis of Furoclausine-A
Publikationsverlauf
Publikationsdatum:
12. Januar 2004 (online)
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Abstract
The first total synthesis of the furo[3,2-a]carbazole alkaloid furoclausine-A is described using an iron-mediated construction of the carbazole framework and an acid-catalyzed annulation of the furan ring as key steps.
Key words
alkaloids - cyclizations - furans - iron - oxidations
Part 70: Knölker, H.-J. Curr. Org. Synthesis 2004, 1, in print.
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References
Part 70: Knölker, H.-J. Curr. Org. Synthesis 2004, 1, in print.
16All new compounds have been fully characterized (UV, IR, 1H NMR, 13C NMR, MS, and elemental analysis).
13C NMR and DEPT spectral data, and elemental analyses. 10: 13C NMR (125 MHz, CDCl3): δ = 15.34 (2 × CH3), 15.57 (CH3), 32.62 (CH2), 37.58 (CH), 53.10 (CH), 54.01 (CH), 54.39 (CH3), 62.70 (2 × CH2), 66.98 (CH), 68.99 (CH2), 100.14 (CH), 100.73 (CH), 116.93 (C), 122.74 (C), 128.50 (CH), 139.93 (C), 142.10 (C), 155.53 (C), 211.25 (3 × CO). Anal. Calcd for C23H29FeNO7: C, 56.69; H, 6.00; N, 2.87. Found: C, 56.77; H, 6.12; N, 2.91.
11: 13C NMR (75 MHz, CDCl3): δ = 15.39 (2 × CH3), 16.68 (CH3), 55.64 (CH3), 62.92 (2 × CH2), 69.36 (CH2), 93.81 (CH), 94.90 (CH), 100.90 (CH), 107.68 (CH), 116.75 (C), 117.41 (C), 119.37 (C), 119.98 (CH), 120.82 (CH), 138.89 (C), 140.56 (C), 155.33 (C), 157.95 (C). Anal. Calcd for C20H25NO4: C, 69.95; H, 7.34; N, 4.08. Found: C, 70.03; H, 7.48; N, 4.15.
12: 13C NMR (125 MHz, CDCl3): δ = 15.42 (CH3), 55.67 (CH3), 95.18 (CH), 103.54 (CH), 108.12 (CH), 111.37 (C), 114.11 (C), 116.06 (CH), 117.94 (C), 118.00 (C), 120.16 (CH), 130.69 (C), 140.01 (C), 143.72 (CH), 153.35 (C), 157.96 (C). Anal. Calcd for C16H13NO2: C, 76.48; H, 5.21; N, 5.57. Found: C, 76.27; H, 5.31; N, 5.74.
O-Methylfuroclausine-A (13): 13C NMR (125 MHz, acetone-d
6): δ = 55.82 (CH3), 96.40 (CH), 104.73 (CH), 110.14 (CH), 113.56 (C), 116.30 (C), 118.31 (C), 119.11 (C), 120.11 (CH), 121.58 (CH), 137.80 (C), 142.31 (C), 146.06 (CH), 154.11 (C), 159.99 (C), 187.79 (CHO). Anal. Calcd for C16H11NO3: 72.45; H, 4.18; N, 5.28. Found: C, 72.31; H, 4.20; N, 5.49.
Experimental Procedure for the Oxidative Cyclization to the Carbazole 11: Iodine (1.18 g, 4.65 mmol) was added to a solution of the iron complex 10 (713 mg, 1.46 mmol) in anhyd pyridine (20 mL) at 90 °C. After stirring for 6 h at 90 °C in the air, the reaction mixture was cooled to r.t., a solution of sodium thiosulfate (2.4 g) and citric acid (1.3 g) in water (24 mL) was added, and the resulting mixture was extracted with Et2O several times. The combined organic layers were washed with water (3 × 30 mL) and dried over MgSO4. Removal of the solvent and purification of the residue by flash chromatography (EtOAc-hexane, 1:1) on silica gel provided the carbazole 11 as colorless crystals; yield: 356 mg (71%); mp: 195-196 °C.
19Amberlyst 15 from Fluka (art. 06423).
20Furoclausine-A (3): Light yellow crystals; mp: 110 °C (dec.). IR (ATR): n = 3302, 1703, 1670, 1619, 1590, 1444, 1350, 1325, 1302, 1276, 1258, 1228, 1165, 1149, 1114, 1070, 1040, 993, 956, 856, 830, 810, 799, 775, 750, 730, 686, 629, 591, 549 cm-1. 1H NMR (500 MHz, acetone-d 6): δ = 6.92 (dd, J = 8.4, 2.1 Hz, 1 H), 7.09 (d, J = 2.1 Hz, 1 H), 7.32 (d, J = 2.2 Hz, 1 H), 8.05 (d, J = 2.2 Hz, 1 H), 8.10 (d, J = 8.4 Hz, 1 H), 8.51 (s, 1 H), 8.54 (s, 1 H), 10.47 (s, 1 H), 11.16 (br s, 1 H). 13C NMR (125 MHz, acetone-d 6): δ = 98.22 (CH), 104.67 (CH), 110.73 (CH), 113.43 (C), 116.16 (C), 117.64 (C), 119.36 (C), 119.85 (CH), 121.62 (CH), 137.75 (C), 142.57 (C), 146.02 (CH), 154.09 (C), 157.49 (C), 187.75 (CHO). UV (MeOH): λ = 220, 235, 287(sh), 300, 345 nm. MS (150 °C): m/z (%) = 251(100) [M+], 250 (74), 222 (26), 194 (11), 139 (3). HRMS: m/z [M+] calcd for C15H9NO3: 251.0582; found: 251.0568.