Palladium-Catalyzed Michael Addition of Indoles to α,β-Unsaturated Ketones in an Ionic Liquid

Abstract

The PdCl₂(CH₃CN)₂-catalyzed Michael addition reaction of indoles with α,β-unsaturated ketones in ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF₄]) to afford the corresponding 3-alkylated indoles in good yields is described. The catalyst system PdCl₂(CH₃CN)₂/[bmim][BF₄] can be recovered and reused.

palladium - indoles - Michael reaction - ionic liquid

References

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9

Indoles 3; General Procedure. The appropriate indole 1 (1.0 mmol), α,β-unsaturated ketone 2 (1.0 mmol), and PdCl₂ (CH₃CN)₂ (2 mol%) were mixed in [bmim][BF₄] (1 mL). The mixture was stirred at 100 °C under N₂ for the appropriate time and the reaction was monitored by TLC. After completion, the products were separated by thorough extraction with a mixture of EtOAc-Et₂O. The solvent was evaporated and pure 3-substituted indole derivatives 3 were obtained by silica gel column chromatography with hexane-EtOAc (3:1). The ionic liquid containing PdCl₂(CH₃CN)₂ was dried under vacuum for the next run. All products gave satisfactory spectroscopic and analytical data. Representative compound 3a: Yield 94%, pale pink solid, mp 136-138 °C, R _f 0.5 (hexane-EtOAc, 3:1). IR (KBr): 3407 (NH), 1675 (C=O) cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 8.04 (br, 1 H), 7.98 (d, J = 7.5 Hz, 2 H), 7.58 (t, J = 7.4 Hz, 1 H), 7.45-7.50 (m, 3 H), 7.40 (2 H, J = 7.4 Hz, 2 H), 7.28-7.34 (m, 3 H), 7.17-7.23 (m, 2 H), 7.07 (t, J = 7.4 Hz, 1 H), 6.99 (s, 1 H), 5.13 (t, J = 7.2 Hz, 1 H), 3.85 (dd, J = 6.8, 6.8 Hz, 1 H), 3.78 (dd, J = 7.6, 7.6 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 198.9, 144.5, 137.3, 136.8, 133.2, 128.8, 128.6, 128.3, 128.0, 126.8, 126.5, 122.3, 121.7, 119.7, 119.6, 119.4, 111.4, 45.4, 38.4. MS (EI): m/z = 325 [M⁺]. HRMS (EI): m/z calcd for C₂₃H₁₉NO [M]⁺: 325.1467, found: 325.1465.

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