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Synlett 2011(14): 2056-2058  
DOI: 10.1055/s-0030-1260972
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Transition Metals in Organic Synthesis, Part 95: [¹] First Total Synthesis of the 1,7-Dioxygenated Carbazole Alkaloids Clausine Q and Clausine R

Müge Fuchsenberger, Ronny Forke, Hans-Joachim Knölker*
Department Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany
Fax: +49(351)46337030; e-Mail: hans-joachim.knoelker@tu-dresden.de;
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Publikationsverlauf

Received 6 June 2011
Publikationsdatum:
25. Juli 2011 (online)

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Abstract

The sequence of palladium(0)-catalyzed amination and palladium(II)-catalyzed oxidative formation of the biaryl bond provides a direct route to the 1,7-dioxygenated tricyclic carbazole alkaloids clausine Q and clausine R.

Key words

alkaloids - catalysis - cyclization - oxidation - palladium

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Experimental Procedure for the Palladium(II)-Catalyzed Oxidative Cyclization of 7: The N,N-diarylamine 7 (301 mg, 0.7 mmol), K2CO3 (9.8 mg, 0.07 mmol), and pivalic acid (680 mg) were heated under air at 130 ˚C. Freshly recrystallized Pd(OAc)2 (8.0 mg, 0.036 mmol) was added and the reaction mixture was heated under air at 130 ˚C with vigorous stirring. After cooling to r.t., the mixture was taken up in EtOAc and washed first with a sat. solution of K2CO3 and then with a sat. solution of NaCl. The aqueous layers were subsequently extracted with EtOAc. The combined organic layers were dried over Na2SO4 and the solvent was removed in vacuum. Purification of the crude product by flash chromatography (pentane-CH2Cl2-EtOAc, gradient elution from 55:5:1 to 25:5:1) on silica
gel provided methyl 7-triisopropylsilyloxy-1-methoxy-carbazole-3-carboxylate (8; yield: 255 mg, 85%) as colorless crystals (mp 164-165 ˚C). UV (MeOH): λmax = 216, 239, 250, 278 (sh), 283, 305 (sh), 318, 330 nm. IR (ATR): 3351, 2941, 2864, 1685, 1609, 1590, 1504, 1457, 1430, 1396, 1346, 1258, 1218, 1163, 1107, 1035, 997, 968, 921, 881, 851, 839, 823, 800, 754, 707, 672, 623 cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 1.13 (d, J = 7.4 Hz, 18 H), 1.31 (sept, J = 7.4 Hz, 3 H), 3.97 (s, 3 H), 4.04 (s, 3 H), 6.86 (dd, J = 8.5, 2.1 Hz, 1 H), 6.96 (d, J = 2.1 Hz, 1 H), 7.53 (d, J = 1.2 Hz, 1 H), 7.89 (d, J = 8.5 Hz, 1 H), 8.31 (br s, 1 H), 8.36 (br s, 1 H). ¹³C NMR and DEPT (125 MHz, CDCl3): δ = 12.71 (3 × CH), 17.95 (6 × Me), 51.98 (Me), 55.72 (Me), 101.84 (CH), 105.93 (CH), 114.11 (CH), 115.47 (CH), 117.91 (C), 121.17 (CH), 121.89 (C), 123.85 (C), 132.85 (C), 140.79 (C), 144.84 (C), 155.58 (C), 168.04 (C=O). MS (EI): m/z (%) = 427 (100) [M+], 396 (8), 385 (21), 384 (71), 356 (23), 352 (42), 328 (17), 314 (15), 296 (9), 282 (19). Anal. Calcd for C24H33NO4Si: C, 67.41; H, 7.78; N, 3.28. Found: C, 67.30; H, 7.94; N, 3.29.

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Manganese dioxide (precipitated, active) from Merck (art. 805958).

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Characteristic Spectroscopic Data of the 1,7-Dioxy-genated Carbazole Alkaloids 3 and 4: Clausine Q (3): colorless crystals; mp 189-191 ˚C (lit.6 85-87 ˚C). UV (MeOH): λmax = 202, 242, 285, 295 (sh), 338 nm. IR (ATR): 3438, 3236, 2930, 2844, 1641, 1609, 1570, 1542, 1484, 1368, 1342, 1298, 1241, 1218, 1155, 1131, 1104, 1030, 954, 881, 829, 810, 780, 704, 666 cm-¹. ¹H NMR (500 MHz, acetone-d 6): δ = 4.07 (s, 3 H), 6.85 (dd, J = 8.5, 2.1 Hz, 1 H), 7.08 (d, J = 2.1 Hz, 1 H), 7.39 (d, J = 1.0 Hz, 1 H), 8.01 (d, J = 8.5 Hz, 1 H), 8.21 (d, J = 1.0 Hz, 1 H), 8.57 (br s, 1 H), 10.02 (s, 1 H), 10.69 (br s, 1 H). ¹³C NMR and DEPT (125 MHz, acetone-d 6): δ = 56.01 (Me), 98.25 (CH), 103.37 (CH), 110.82 (CH), 117.35 (C), 119.25 (CH), 122.09 (CH), 125.04 (C), 131.03 (C), 134.74 (C), 142.92 (C), 146.89 (C), 158.09 (C), 191.87 (CHO). MS (EI): m/z (%) = 241 (100) [M+], 240 (20), 226 (28), 212 (10), 198 (12), 170 (44). Anal. Calcd for C14H11NO3: C, 69.70; H, 4.60; N, 5.81. Found: C, 69.20; H, 4.35; N, 5.27.
Clausine R (4): colorless crystals; mp 293-295 ˚C (lit.6 178-181 ˚C). UV (MeOH): λmax = 214, 240, 251, 282, 305 (sh), 319, 333 nm. IR (ATR): 3439, 3355, 3303, 3011, 2956, 2923, 2852, 1658, 1644, 1631, 1618, 1594, 1490, 1456, 1435, 1390, 1360, 1334, 1311, 1268, 1233, 1169, 1087, 995, 963, 925, 882, 824, 798, 767, 751 cm-¹. ¹H NMR (500 MHz, acetone-d 6): δ = 3.87 (s, 3 H), 6.81 (dd, J = 8.5, 2.1 Hz, 1 H), 7.04 (d, J = 2.1 Hz, 1 H), 7.50 (d, J = 1.1 Hz, 1 H), 7.97 (d, J = 8.5 Hz, 1 H), 8.24 (d, J = 1.1 Hz, 1 H), 8.47 (s, 1 H), 8.95 (s, 1 H), 10.38 (br s, 1 H). ¹³C NMR and DEPT (125 MHz, acetone-d 6): δ = 51.83 (Me), 98.01 (CH), 110.21 (CH), 110.49 (CH), 114.38 (CH), 117.51 (C), 121.95 (CH), 122.32 (C), 125.46 (C), 133.41 (C), 142.87 (C), 143.01 (C), 157.91 (C), 168.05 (C=O). MS (EI): m/z (%) = 257 (100) [M+], 226 (67), 198 (28), 170 (14). Anal. Calcd for C14H11NO4: C, 65.37; H, 4.31; N, 5.44. Found: C, 65.24; H, 4.95; N, 5.03.