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Synlett 2010(2): 211-214  
DOI: 10.1055/s-0029-1218573
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Novel Annulated Hymenialdisine Analogues via Palladium-Catalyzed Cross-Coupling Reactions with Aryl Boronic Acids

Naveenkumar Mangua,b, Anke Spannenberga, Matthias Bellera,b, Man-Kin Tse*a,b
a Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
b Center for Life Science Automation (CELISCA), Universität Rostock, Friedrich-Barnewitz-Str. 8, 18119 Rostock-Warnemünde, Germany
Fax: +49(381)128151158; e-Mail: man-kin.tse@catalysis.de;
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Publication History

Received 14 October 2009
Publication Date:
14 December 2009 (online)

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Abstract

Palladium-catalyzed Suzuki cross-coupling reactions of an indole vinyl triflate provides an efficient pathway for the synthesis of a diverse class of novel hymenialdisine analogues.

Key words

hymenialdisine analogues - cross-coupling - silica gel - palladium - heterocycles

    References and Notes

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15

Decomposition of compound 8 was observed on storage (˜5 d).

17

General procedure for the Suzuki coupling of 8 with aryl boronic acids 9a-k: To a stirring mixture of 8 (600 mg, 1.1 mmol) in toluene (3 mL) and absolute EtOH (3 mL) under an argon atmosphere, Pd(PPh3)4 (12.6 mg, 0.011 mmol), boronic acid (1.2 mmol) and 2 M aq Na2CO3 solution (0.55 mL) were added. The mixture was heated at 70 ˚C overnight (˜12-16 h), then the solvent was removed under reduced pressure and the mixture was extracted with CH2Cl2 (2 × 20 mL), the combined organic extracts were washed with brine (25 mL), dried over MgSO4 and concentrated under reduced pressure to give the crude product, which was used for the deprotection step without further purification. The above crude product was dissolved in anhydrous CH2Cl2 (50 mL) and activated silica (2.46 g, 0.040-0.063 mm) was added. The solvent was removed under reduced pressure and the solid mixture was heated under argon at 100 ˚C for 1 h. Purification by column chromatography (silica gel 70-230 mesh, hexane-EtOAc, 6:4) yielded pure compounds 9a-k.

18

X-ray crystal data for 9d: Empirical formula: C19H16N2O2; M r = 304.34; monoclinic; space group: P21/c; cell dimensions: a = 9.3756 (3), b = 6.5948 (2), c = 25.3990 (8) Å, β = 100.003 (2)˚; V = 1546.55 (8) ų; Z = 4; ρ calcd = 1.307 g˙cm-³; 22763 reflections measured, 3292 independent reflections, of which 2312 were observed [I >2σ(I)], final R indices [I >2σ(I)]: R 1 = 0.0306, wR 2 = 0.0686, R indices (all data): R 1 = 0.0486, wR 2 = 0.0715, 217 refined parameters. Data were collected on a STOE IPDS II diffractometer using graphite-monochromated MoKα radiation. The structure was solved by direct methods (SHELXS-97)¹9 and refined by full-matrix least-squares techniques on F ² (SHELXL-97).¹9 XP (Bruker AXS) was used for graphical represen-tation. CCDC 748111 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallo-graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.