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DOI: 10.1055/s-0030-1260972
Transition Metals in Organic Synthesis, Part 95: [¹] First Total Synthesis of the 1,7-Dioxygenated Carbazole Alkaloids Clausine Q and Clausine R
Publikationsverlauf
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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References and Notes
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.
Manganese dioxide (precipitated, active) from Merck (art. 805958).
18
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.