Transition Metal Complexes in Organic Synthesis, Part 71: [1] First Total Synthesis of Furoclausine-A

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.

alkaloids - cyclizations - furans - iron - oxidations

References

1

Part 70: Knölker, H.-J. Curr. Org. Synthesis 2004, 1, in print.

2 Chakraborty DP. In The Alkaloids   Vol. 44:  Cordell GA. Academic Press; New York: 1993.  p.257 

3 Kirsch GH. Curr. Org. Chem.  2001,  5:  507 

4 Knölker H.-J. Reddy KR. Chem. Rev.  2002,  102:  4303 

5 Chakraborty DP. Roy S. In Prog. Chem. Org. Nat. Prod.   Vol. 85:  Herz W. Grisebach H. Kirby GW. Steglich W. Tamm C. Springer; Wien: 2003.  p.125 

6 Ito C. Furukawa H. Chem. Pharm. Bull.  1990,  38:  1548 

7 Wu T.-S. Huang S.-C. Wu P.-L. Heterocycles  1997,  45:  969 

8a Knölker H.-J. Fröhner W. Tetrahedron Lett.  1996,  37:  9183 

8b Knölker H.-J. Fröhner W. Synthesis  2000,  2131 

9a Hagiwara H. Choshi T. Fujimoto H. Sugino E. Hibino S. Chem. Pharm. Bull.  1998,  46:  1948 

9b Hagiwara H. Choshi T. Nobuhiro J. Fujimoto H. Hibino S. Chem. Pharm. Bull.  2001,  49:  881 

10 Beccalli EM. Clerici F. Marchesini A. Tetrahedron  1998,  54:  11675 

11 Soós T. Timári G. Hajós G. Tetrahedron Lett.  1999,  40:  8607 

12 Yasuhara A. Suzuki N. Sakamoto T. Chem. Pharm. Bull.  2002,  50:  143 

13a Knölker H.-J. Synlett  1992,  371 

13b Knölker H.-J. In Transition Metals for Organic Synthesis   Vol. 1:  Beller M. Bolm C. Wiley-VCH; Weinheim: 1998.  p.534 

13c Knölker H.-J. Chem. Soc. Rev.  1999,  28:  151 

14a Knölker H.-J. Ahrens B. Gonser P. Heininger M. Jones PG. Tetrahedron  2000,  56:  2259 

14b Knölker H.-J. Chem. Rev.  2000,  100:  2941 

15 Birch AJ. Cross PE. Lewis J. White DA. Wild SB. J. Chem. Soc. A  1968,  332 

16

All 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.

17

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.

18 Röhrkasten R. Konrad M. In Methoden der Organischen Chemie (Houben-Weyl)   Vol. E6b:  Kreher RP. Thieme; Stuttgart: 1994.  p.94 

19

Amberlyst 15 from Fluka (art. 06423).

20

Furoclausine-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.