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

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.

heterocycles - indole - palladium - synthesis

References

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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.