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Synlett 2012; 23(8): 1230-1234
DOI: 10.1055/s-0031-1290968
letter
© Georg Thieme Verlag Stuttgart · New York

Transition Metals in Organic Synthesis, Part 100:[ 1 ] Highly Efficient Palla­dium(II)-Catalyzed Oxidative Cyclization to the 1,7,8-Trioxygenated Carbazole Alkaloid Murrayastine

Laurent Huet
Department Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany, Fax: +49(351)46337030   Email: hans-joachim.knoelker@tu-dresden.de
,
Ronny Forke
Department Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany, Fax: +49(351)46337030   Email: hans-joachim.knoelker@tu-dresden.de
,
Anne Jäger
Department Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany, Fax: +49(351)46337030   Email: hans-joachim.knoelker@tu-dresden.de
,
Hans-Joachim Knölker*
Department Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany, Fax: +49(351)46337030   Email: hans-joachim.knoelker@tu-dresden.de
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Further Information

Publication History

Received: 14 March 2012

Accepted after revision: 03 April 2012

Publication Date:
26 April 2012 (online)

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Abstract

Consecutive palladium-catalyzed C–N and C–C bond formation provides an efficient route to the 1,7,8-trioxygenated carbazole alkaloid murrayastine.

Key words

alkaloids - catalysis - cyclization - palladium
 

  • References and Notes

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  • 22 Characteristic spectroscopic data for the diarylamine 8: pale yellow solid; mp 78 °C. IR (ATR): n = 3413, 3003, 2968, 2931, 2854, 2836, 1601, 1586, 1498, 1478, 1464, 1447, 1421, 1401, 1336, 1297, 1251, 1220, 1190, 1165, 1134, 1082, 1037, 993, 916, 934, 838, 808, 773, 739 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.33 (s, 3 H), 3.857 (s, 3 H), 3.863 (s, 3 H), 3.88 (s, 3 H), 5.90 (br s, 1 H), 6.46 (m, 1 H), 6.72–6.73 (m, 2 H), 6.92 (d, J = 2.4 Hz, 1 H), 6.93 (s, 1 H), 7.28 (d, J = 8.3 Hz, 1 H). 13C NMR and DEPT (125 MHz, CDCl3): δ = 21.20 (Me), 55.60 (Me), 55.78 (Me), 60.23 (Me), 103.44 (CH), 107.98 (CH), 111.78 (CH), 117.50 (CH), 120.80 (CH), 123.85 (CH), 129.38 (C), 130.90 (C), 137.46 (C), 138.01 (C), 149.64 (C), 153.00 (C). MS (EI): m/z (%) = 273 (72) [M+], 258 (7), 243 (8), 227 (100), 184 (11). Anal. Calcd for C16H19NO3: C, 70.31; H, 7.01; N, 5.12. Found: C, 70.33; H, 6.87; N, 5.13
  • 23 Sridharan V, Martín MA, Menéndez JC. Synlett 2006; 2375
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  • 25 Experimental Procedure for the Palladium(II)-Catalyzed Oxidative Cyclization to Murrayastine (1): The diarylamine 8 (200 mg, 0.732 mmol), K2CO3 (5.4 mg, 0.039 mmol) and pivalic acid (500 mg) were placed in a 10-mL test tube. The mixture was heated at 120 °C under air and recrystallized Pd(OAc)2 (5.0 mg, 0.022 mmol) was added. After 20 h of vigorous stirring at 120 °C in the presence of air, the reaction mixture was cooled to r.t. The residue was dissolved in EtOAc and washed several times with a sat. solution of K2CO3 and then with brine. After extraction with EtOAc, the combined organic layers were dried over Na2SO4. Removal of the solvent and flash chromatography (pentane–CH2Cl2–EtOAc, gradient elution from 40:5:1 to 18:5:1) on silica gel provided murrayastine (1; yield: 160 mg, 81%) and 3-(pivaloyloxymethyl)-1,7,8-trimethoxy-9H-carbazole (9; yield: 9.4 mg, 3%)
  • 26 Characteristic spectroscopic data for murrayastine (1): light yellow crystals; mp 101–102 °C. UV (MeOH): λmax = 223, 245, 253, 297, 321, 334 nm. IR (ATR): n = 3398, 3343, 3247, 2955, 2921, 2851, 1633, 1583, 1498, 1462, 1440, 1418, 1383, 1344, 1281, 1250, 1221, 1209, 1179, 1134, 1088, 1065, 1031, 1021, 971, 935, 819, 781 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.51 (s, 3 H), 3.97 (s, 3 H), 3.99 (s, 3 H), 4.02 (s, 3 H), 6.69 (s, 1 H), 6.86 (d, J = 8.5 Hz, 1 H), 7.38 (s, 1 H), 7.65 (d, J = 8.5 Hz, 1 H), 8.22 (br s, 1 H). 13C NMR and DEPT (125 MHz, CDCl3): δ = 21.90 (Me), 55.46 (Me), 56.77 (Me), 60.85 (Me), 106.10 (CH), 107.12 (CH), 112.21 (CH), 115.50 (CH), 119.57 (C), 124.79 (C), 128.09 (C), 129.58 (C), 133.84 (C), 134.21 (C), 145.24 (C), 149.99 (C). MS (EI): m/z (%) = 271 (100) [M+], 256 (46), 213 (46), 170 (19). Anal. Calcd for C16H17NO3: C, 70.83; H, 6.32; N, 5.16. Found: C, 71.04; H, 6.51; N, 4.90
  • 27 Crystal data for murrayastine (1): C16H17NO3, crystal size: 0.25 × 0.24 × 0.23 mm3, M = 271.31 g mol–1, orthorhombic, space group: Pbca, λ = 0.71073 Å, a = 9.158(1), b = 11.517(1), c = 26.488(3) Å, V = 2793.8(5) Å3, Z = 8, D calcd = 1.290 g cm–3, μ = 0.089 mm–1, T = 198(2) K, θ range = 3.23–27.00°; reflections collected: 23879, independent: 3044 (R int = 0.0611), 189 parameters. The structure was solved by direct methods and refined by full-matrix least-squares on F 2; final R indices [I > 2σ(I)]: R 1 = 0.0566, wR 2 = 0.1022; maximal residual electron density: 0.198 e Å–3. CCDC 870640 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.uk/data_request/cif
  • 28 Characteristic spectroscopic data for 3-(pivaloyloxymethyl)-1,7,8-trimethoxy-9H-carbazole (9): yellow solid. 1H NMR (600 MHz, CDCl3): δ = 1.24 (s, 9 H), 3.98 (s, 3 H), 4.01 (s, 3 H), 4.02 (s, 3 H), 5.25 (s, 2 H), 6.85 (s, 1 H), 6.89 (d, J = 8.5 Hz, 1 H), 7.57 (s, 1 H), 7.68 (d, J = 8.5 Hz, 1 H), 8.36 (br s, 1 H). 13C NMR and DEPT (150 MHz, CDCl3): δ = 27.20 (3 × Me), 38.79 (C), 55.55 (Me), 56.77 (Me), 60.89 (Me), 67.18 (CH2), 105.95 (CH), 106.51 (CH), 112.74 (CH), 115.64 (CH), 119.48 (C), 124.54 (C), 128.32 (C), 129.73 (C), 133.89 (C), 134.22 (C), 145.46 (C), 150.20 (C), 178.50 (C=O). MS (EI): m/z (%) = 371 (55) [M+], 270 (100)