Ultrasound-accelerated Michael Addition of Indole to α,β-Unsaturated Ketones Catalyzed by Ceric Ammonium Nitrate (CAN)

Abstract

Ceric ammonium nitrate efficiently catalyzes the Michael addition of indole to α,β-unsaturated carbonyl ketones by means of alkylation of indole under ultrasonic irradiation to afford the corresponding adduct in excellent yields. The substitution on the indole nucleus occurred exclusively at the 3-position, and N-alkylation products have not been observed.

ceric ammonium nitrate - ultrasound - indole - Michael reaction

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Typical experimental procedure: A mixture of indole (0.117 g, 1 mmol), 2a (0.208 g, 1 mmol), CAN (0.056 g, 0.1 mmol) and anhydrous CH₃OH (2 mL) was irradiated in the presence of ultrasound in an open vessel at room temperature until the disappearance of the starting indole (3 h, checked by TLC). After standing 3 h, the reaction mixture was washed with cold H₂O (3 × 15 mL), warm H₂O (2 × 10 mL) and cold CH₃CH₂OH (3 × 0.5 mL). The crude mixture recrystallized from CH₃CH₂OH and the residue was purified by flash chromatography to afford the pure product 3a (0.280 g, yield: 81%).
3-(3-Indolyl)-1,3-diphenylpropan-2-one, 3a: colorless needles; mp: 125-127 °C (lit. [5b] 131-132 °C); IR (KBr): υ 1679 (CO), 3413 (NH) cm^-1; ¹H NMR (400 MHz, CDCl₃): δ 3.67-3.83 (m, 2 H, CH₂), 5.04 (t, J = 7.2 Hz, 1 H, CH), 6.97-7.53 (m, 13 H), 7.91-7.96 (m, 3 H).
HRMS: m/z calcd for C₂₃H₁₉NO: 325.1467; found: 325.1431.
Anal. Calcd for C₂₃H₁₉NO: C, 84.89; H, 5.89; N, 4.30. Found: C, 84.74; H, 5.84; N, 4.35.