Synlett 2004(5): 0907-0909  
DOI: 10.1055/s-2004-820039
LETTER
© Georg Thieme Verlag Stuttgart · New York

Novel Synthesis of Fused Indoles by the Palladium-Catalyzed Cyclization of N-Cycloalkenyl-o-haloanilines

Takeshi Watanabe, Shigeru Arai, Atsushi Nishida*
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Fax: +81(43)2902909; e-Mail: nishida@p.chiba-u.ac.jp;
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Publikationsverlauf

Received 17 November 2003
Publikationsdatum:
23. März 2004 (online)

Abstract

A new palladium-catalyzed cyclization of N-alkenyl-o-haloanilines with selective isomerization of a double bond followed by 5-endo cyclization was developed and used to synthesize fused indoles.

5

While other silver salts, such as Ag2CO3, AgPF6, AgOTf, and AgBF4, also promoted this reaction, they were less effective.

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Experimental Procedure for the Synthesis of 13: A mixture of enamine 12 (0.15 g, 0.28 mmol), Ag3PO4 (0.12 g, 0.28 mmol), and Pd(PPh3)4 (32 mg, 28 µmol) was heated (18 h) with stirring in DMSO (1.0 mL) at 100 °C under Ar. The mixture was diluted with Et2O at r.t., and filtered through a celite pad. The filtrate was concentrated and the residue was purified by silica gel column chromatography (EtOAc:n-hexane, 1:5) to give 13 as a colorless oil (79 mg, 69%). 1H NMR (600 MHz, CDCl3): δ = 1.35 (t, J = 7.1 Hz, 3 H), 1.87 (td, J = 2.8, 12.9 Hz, 1 H), 2.18 (ddd, J = 3.9, 12.6, 14.8 Hz, 1 H), 2.56 (t, J = 12.1 Hz, 1 H), 2.66 (tt, J = 5.0, 12.9 Hz, 1 H), 2.94 (ddd, J = 3.0, 12.1, 15.1 Hz, 1 H), 3.13 (ddd, J = 1.4, 3.6, 15.1 Hz, 1 H), 3.48 (dd, J = 4.1, 15.1 Hz, 1 H), 4.12 (dt, J = 3.9, 13.2 Hz, 1 H), 4.24-4.32 (m, 2 H), 4.37 (dd, J = 5.2, 12.7 Hz, 1 H), 7.06 (td, J = 1.1, 7.1 Hz, 1 H), 7.13 (td, J = 1.1, 8.0 Hz, 1 H), 7.33 (d, J = 8.0 Hz, 1 H), 7.42 (d, J = 8.0 Hz, 1 H), 7.47 (td, J = 1.4, 7.7 Hz, 2 H), 7.54 (tt, J = 1.4, 7.2 Hz, 1 H), 7.78-7.80 (m, 2 H), 9.11 (s, 1 H). 13C NMR (150 MHz, CDCl3): δ = 14.3, 25.8, 36.5, 39.4, 48.5, 53.7, 61.6, 111.2, 111.3, 117.6, 119.5, 121.9, 127.0, 129.2, 130.9, 132.7, 135.5, 139.1, 174.8.