Palladium-Catalyzed Regioselective Hydroarylation of Ynamides with Aryl Iodides: Easy Synthesis of Various Substituted Enamides Containing Stilbene Derivatives

Abstract

Palladium-catalyzed hydroarylation of ynamides has been developed. The desired coupling products were obtained in good yields and with high regioselectivities. Various aryl iodides can be used in this reaction, permitting the syntheses of many different kinds of enamides from ynamides.

Key words

ynamides - hydroarylation - palladium catalysis - cross-coupling - enamides - arylation

• References and Notes


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• 10 Ethyl 4-[(1Z)-1-{Benzyl[(4-tolyl)sulfonyl]amino}oct-1-en-1-yl]benzoate (3a) and Ethyl 4-[(E)-2-{Benzyl[(4-tolyl)sulfonyl]amino}-1-hexylvinyl]benzoate (4a); Typical Procedure Ethyl 4-iodobenzoate (2a; 0.21 mL, 1.23 mmol, 3.0 equiv) was added a solution of ynamide 1a (150.0 mg, 0.41 mmol), Pd(OAc)₂ (4.6 mg, 20.5 μmol, 5 mol%), DPPF (11.4 mg, 20.5 μmol, 5 mol%), and HCO₂NH₄ (77.6 mg, 1.23 mmol, 3.0 equiv) in DMF (20 mL) at 0 °C under argon. The mixture was stirred at 100 °C for 18 h and then cooled to 0 °C. H₂O (22 mL) was added, and the aqueous phase was extracted with Et₂O (3 × 50 mL). The organic phases were combined, washed with brine (1 × 50 mL), and dried (Na₂SO₄). The volatiles were removed under reduce pressure, and the residue was purified by column chromatography [silica gel, hexane–Et₂O (20:1) to hexane–EtOAc (10:1)] to afford 3a, 4a, and recovered 1a (6.0 mg; 4%). 3a: off-white solid; yield: 161.1 mg (76%); mp 71 °C. IR (KBr): 3059, 2921, 1705, 1605 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 0.88 (t, J = 7.2 Hz, 3 H), 1.04–1.28 (m, 8 H), 1.38 (t, J = 7.2 Hz, 3 H), 1.92 (br s, 2 H), 2.48 (s, 3 H), 4.14 (br s, 1 H), 4.36 (q, J = 7.2 Hz, 2 H), 4.71 (br s, 1 H), 6.11 (t, J = 7.4 Hz, 1 H), 7.06–7.12 (m, 4 H), 7.21–7.23 (m, 3 H), 7.35 (d, J = 7.6 Hz, 2 H), 7.81–7.85 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.0, 14.3, 21.5, 22.5, 28.7, 29.1, 29.9, 31.6, 52.4, 60.9, 126.4, 127.6, 128.0, 128.2, 129.3, 129.5, 129.5, 129.7, 134.6, 135.5, 137.3, 137.9, 141.7, 143.6, 166.2. EI-LRMS: m/z = 519 [M⁺], 364, 155, 91. EI-HRMS; m/z [M⁺] calcd for C₃₁H₃₇NO₄S: 519.2443; found: 519.2442. 4a: off-white solid; yield: 31.9 mg (15%); mp 73–74 °C. IR (KBr): 2929, 1716, 1607 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 0.65–0.75 (m, 2 H), 0.81 (t, J = 7.2 Hz, 3 H), 0.97–1.05 (m, 4 H), 1.10–1.18 (m, 2 H), 1.38 (t, J = 7.2 Hz, 3 H), 2.42–2.49 (m, 2 H), 2.44 (s, 3 H), 4.25 (s, 2 H), 4.36 (q, J = 7.2 Hz, 2 H), 5.32 (s, 1 H), 7.17 (d, J = 8.2 Hz, 2 H), 7.26–7.35 (m, 7 H), 7.70 (d, J = 8.2 Hz, 2 H), 7.95 (d, J = 8.2 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.0, 14.3, 21.5, 22.5, 27.2, 29.3, 29.8, 31.5, 55.2, 60.9, 123.7, 126.8, 127.6, 127.9, 128.4, 129.3, 129.5, 129.7, 129.7, 134.7, 135.5, 143.7, 144.0, 149.2, 166.3. EI-LRMS: m/z: 519 [M⁺], 364, 155, 91. EI-HRMS: m/z [M⁺] calcd for C₃₁H₃₇NO₄S: 519.2443; found: 519.2423