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

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
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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): λ_max = 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) ų, 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)

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