Palladium-Catalyzed Heck-Type Coupling via C–N Cleavage

Abstract

A palladium-catalyzed Heck-type coupling method between arenes and ketone Mannich bases via C–N cleavage to synthesize chalcones is reported. This protocol offers good yields and tolerates a broad range of functional groups. Based on the extensive experimental data, we propose a plausible coulping mechanism.

Key words

palladium-catalyzed - Heck-type coupling - C–N cleavage - control experiment - mechanism

• References and Notes

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• 18 Synthesis of 3a–p A mixture of 1 (0.2 mmol), 2 (0.6 mmol), DMSO (3 mL), Pd(OAc)₂ (5 mol%), and Ag₂CO₃ and Ag₂O (1.5 equiv, 1:1) was stirred at 120 °C under air atmosphere for 24 h. To the reaction mixture was added H₂O and EtOAc, and the aqueous phase was extracted with EtOAc (3×). The combined organic layer was washed with brine, dried over Na₂SO₄, and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography to give the corresponding products (3a,¹² 3g,¹³ 3h,¹⁴ 3i–l,⁹ 3m,¹⁶ 3n,¹⁷ 3p,q,s–v ⁹ according to the literature). (E)-3-(2,3,4,6-Tetrafluorophenyl)-1-phenylprop-2-en-1-one (3b) Yield 74%. ¹H NMR (500 MHz, CDCl₃): δ = 7.85 (d, J = 7.2 Hz, 2 H), 7.78–7.50 (m, 4 H), 7.35 (d, J = 16.8 Hz, 1 H), 7.08 (m, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 190.2, 153.0 (dm, J = 248.0 Hz), 149.9 (dm, J = 251.0 Hz), 148.5 (dm, J = 249.6 Hz), 139.2 (dm, J = 241.2 Hz), 136.8, 135.9 (m), 131.5, 128.6, 126,9, 115.8, 114.1 (m), 102.9 (m). ¹⁹F NMR (282 MHz, CDCl₃): δ = –118.5 (t, J = 9.6 Hz, 1 F), –134.9 (m, 1 F), –138.7 (dd, J = 19.5, 5.5 Hz, 1 F), –163.8 (m, 1 F). HRMS: m/z calcd for C₁₅H₈OF₄: 280.0511; found: 280.0517. (E)-3-(2,4,6-Trifluorophenyl)-1-phenylprop-2-en-1-one (3c) Yield 71%. ¹H NMR (500 MHz, CDCl₃): δ = 7.84 (d, J = 7.0 Hz, 2 H), 7.62–7.50 (m, 4 H), 7.34 (d, J = 16.6 Hz, 1 H), 6.96 (t, J = 9.0 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 189.8, 165.2 (dm, J = 248.8 Hz), 139.1, 135.8 (m), 130.5, 128.9, 127.8, 117.1, 111.9 (m), 101.9 (m). ¹⁹F NMR (282 MHz, CDCl₃): δ = –105.7 (m, 1 F), –113.1 (t, J = 8.2 Hz, 2 F). HRMS: m/z calcd for C₁₅H₉OF₃: 262.0605; found: 262.0613. (E)-3-(2,3,5,6-Tetrafluorophenyl)-1-phenylprop-2-en-1-one (3d) Yield 79%. ¹H NMR (500 MHz, CDCl₃): δ = 7.837–7.75 (m, 3 H), 7.68–7.59 (m, 3 H), 7.35 (d, J = 17.4 Hz, 1 H), 7.15 (m, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 190.3, 149.5 (dm, J = 256.4 Hz), 145.8 (dm, J = 262.5 Hz), 138.7 (m), 137.1, 128.5, 127.6, 118.3 (m), 114.5, 103.6 (t, J = 22.8 Hz). ¹⁹F NMR (282 MHz, CDCl₃): δ = –139.7 (m, 2 F), –144.8 (m, 2 F). HRMS: m/z calcd for C₁₅H₈OF₄: 280.0511; found: 280.0508. (E)-3-(4-Cyano-2,3,5,6-tetrafluorophenyl)-1-phenylprop-2-en-1-one (3e) Yield 77%. ¹H NMR (500 MHz, CDCl₃): δ = 8.04–8.02 (m, 2 H), 7.98 (d, J = 16.0 Hz, 1 H), 7.78 (d, J = 16.0 Hz, 1 H), 7.67–7.55 (m, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 188.9, 148.5 (dm, J = 246.3 Hz), 145.3 (dm, J = 257.9 Hz), 138.5 (m), 135.4, 129.9, 128.3, 128.4, 127.5, 116.1 (t, J = 13.7 Hz), 114.7, 99.3 (m). ¹⁹F NMR (282 MHz, CDCl₃): δ = –132.5 (dd, J = 21.6, 8.0 Hz, 2 F), –138.4 (dd, J = 21.6, 8.2 Hz, 2 F). HRMS: m/z calcd for C₁₆H₇ONF₄: 305.0464; found: 305.0471. (E)-3-(5-Methyl-2-thienyl)-1-(4-nitrophenyl)-2-propen-1-one (3r) Yield 79%. ¹H NMR (500 MHz, CDCl₃): δ = 8.14 (d, J = 8.0 Hz, 2 H), 7.95 (d, J = 15.4 Hz, 1 H), 7.68 (d, J = 8.0 Hz, 2 H), 7.34 (d, J = 3.6 Hz, 1 H), 7.25 (d, J = 15.4 Hz, 1 H), 6.88 (d, J = 3.6 Hz, 1 H), 2.62 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 189.8, 146.8, 140.2, 140.0, 139.3, 137.5, 134.2, 129.9, 128.5, 127.3, 118.4, 16.1. HRMS: m/z calcd for C₁₄H₁₁NO₃S: 273.0460; found: 273.0465.