Palladium-Catalyzed Tandem Approach to 3-(Diarylmethylene)oxindoles Using Microwave Irradiation

Abstract

We developed a rapid and efficient microwave-assisted tandem reaction for the synthesis of 3-(diarylmethylene)oxindoles. Three palladium-catalyzed reactions (Sonogashira, Heck, and Suzuki–Miyaura reactions) were combined under microwave irradiation conditions to produce 3-(diarylmethylene)oxindoles from simple propiolamides, aryl iodides, and arylboronic acids. The addition of Ag₃PO₄ enhanced the yield and stereoselectivity of the tandem reaction significantly.

Key words

microwave irradiation - Sonogashira reaction - Heck reaction - Suzuki–Miyaura reaction - tandem reaction

• References and Notes


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• 10 Palladium-Catalyzed Tandem Reaction under Microwave Irradiation; General Procedure: A microwave reaction vial was charged with N-methylpropiolamide (0.5 mmol, 1.0 equiv), aryl iodide (0.55 mmol, 1.1 equiv), aryl boronic acid (0.65 mmol, 1.3 equiv), CuI (0.025 mmol, 5 mol%), NaOAc (1.5 mmol, 3.0 equiv), Pd(PPh₃)₄ (0.05 mmol, 10 mol%), Ag₃PO₄ (0.55 mmol, 1.1 equiv), and DMF (5 mL). The reaction vial was sealed and exposed to microwave irradiation conditions for the indicated time and temperature. The mixture was cooled to 25 °C and diluted with EtOAc (200 mL). The organic layer was washed with H₂O (3 × 30 mL) and brine (30 mL), then dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography (silica gel; hexane–EtOAc) to give 3-(diarylmethylene)oxindoles 6 and 9. (Z)-3-[(3-Methoxyphenyl)(phenyl)methylene]-1-methylindolin-2-one [(Z)-9k]: Yellow solid; mp 118.2 °C; R_f = 0.21 (silica gel; hexanes–EtOAc, 4:1). IR (film): 3535, 3055, 2927, 2214, 1700, 1604, 1096, 734 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.43–7.41 (m, 3 H), 7.33–7.29 (m, 3 H), 7.15 (td, J = 7.7, 1.0 Hz, 1 H), 6.95 (d, J = 7.8 Hz, 1 H), 6.91 (dd, J = 8.3, 1.9 Hz, 1 H), 6.83 (t, J = 1.9 Hz, 1 H), 6.76 (d, J = 7.8 Hz, 1 H), 6.66 (td, J = 7.7, 1.0 Hz, 1 H), 6.42 (d, J = 7.6 Hz, 1 H), 3.76 (s, 3 H), 3.20 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 166.8, 159.3, 154.3, 143.5, 141.5, 141.3, 129.3, 129.3, 129.1, 128.9, 128.9, 124.5, 123.3, 122.5, 121.5, 115.7, 114.4, 107.8, 55.4, 26.0. HRMS (EI): m/z calcd for C₂₃H₁₉NO₂: 341.1416; found: 341.1422. (E)-3-[(3-Methoxyphenyl)(phenyl)methylene]-1-methylindolin-2-one [(E)-9k]: Yellow solid; mp 53.0 °C; R_f = 0.26 (silica gel; hexanes–EtOAc, 4:1). IR (film): 3287, 3055, 2937, 1700, 1604, 1469, 1094, 698 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.37–7.33 (m, 6 H), 7.16 (td, J = 7.7, 1.1 Hz, 1 H), 6.98 (ddd, J = 8.3, 2.6, 0.9 Hz, 1 H), 6.77 (dt, J = 9.9, 1.9 Hz, 1 H), 6.84 (dd, J = 2.5, 1.6 Hz, 1 H), 6.76 (d, J = 7.8 Hz, 1 H), 6.69 (td, J = 7.7, 1.0 Hz, 1 H), 6.48 (d, J = 7.3 Hz, 1 H), 3.77 (s, 3 H), 3.20 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 166.9, 160.1, 154.4, 143.5, 142.7, 139.9, 130.2, 130.0, 129.2, 128.9, 128.0, 124.4, 123.5, 123.3, 121.7, 121.6, 115.0, 114.5, 107.8, 55.5, 26.0. HRMS (EI): m/z [M⁺] calcd for C₂₃H₁₉NO₂: 341.1416; found 341.1417.