Synthesis of Enaminones by a Palladium-Catalyzed Four-Component Carbonylative Addition Reaction

Abstract

A palladium-catalyzed carbonylative addition reaction of aryl bromides, amines, and alkynes has been developed. The reaction ­occurs readily in N,N-dimethylformamide with PdCl₂(PPh₃)₂ as a catalyst to give the corresponding enaminones in medium to excellent yields. Furthermore, a mechanism for the palladium-catalyzed four-component carbonylative addition reaction is proposed.

Key words

palladium catalysis - multicomponent reaction - carbonylative addition - enaminones - aryl bromides - amines

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• 12 Enaminones 4a–z; General Procedure A mixture of the appropriate aryl bromide 1 (0.5 mmol), alkyne 2 (0.6 mmol), amine 3 (0.75 mmol), PdCl₂(PPh₃)₂ (17.5 mg, 5 mol%), Et₃N (209 μL, 1.5 mmol), and DMF (4.0 mL) was placed in a 25 mL autoclave under N₂. The autoclave was filled with CO to 5 atm pressure, and heated to 120 °C for 20 h. The product was extracted with EtOAc (3 × 5 mL), and the organic layers were combined, washed with brine (2 × 5 mL), dried (Na₂SO₄), and concentrated under reduced pressure. The residue was then purified by chromatography (silica gel). 1-(4-Acetylphenyl)-3-(diethylamino)-3-phenylprop-2-en-1-one (4a) Pale-yellow solid; yield: 138.2 mg (86%,); mp 96−98 °C. IR (neat): 3474, 3059, 2976, 1683, 1625, 1479, 1461, 1439, 1357, 1265, 1213, 775 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.92 (d, J = 8.0 Hz, 2 H), 7.87 (d, J = 8.0 Hz, 2 H), 7.45–7.23 (m, 5 H), 5.93 (s, 1 H), 3.51–2.90 (m, 4 H), 2.59 (s, 3 H), 1.47–0.94 (m, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 198.0, 185.9, 164.1, 146.2, 138.2, 137.0, 128.7, 128.5, 128.1, 127.8, 127.7, 93.1, 44.8, 26.9, 14.4. HRMS (EI): m/z [M⁺] calcd for C₂₁H₂₃NO₂: 321.1729; found: 321.1735.