Palladium-Catalyzed Heck Reaction of Aryl Bromides in Aqueous Media Using Tris(N-Heterocyclic Carbene) Ligands

Abstract

A highly effective, easy to handle and environmentally benign process for palladium-mediated Heck reaction was developed. The in situ prepared three-component system composed of palladium(II) acetate, a tris(azolinium) bromide and potassium tert-butoxide, quantitatively catalyzes the Heck reaction of aryl bromides in aqueous media.

Heck reaction - imidazolinium and benzimidazolium salts - C-C coupling - palladium - N-heterocyclic carbene

References and Notes

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<A NAME="RS08406ST-13">13</A>

General Procedure for the Synthesis of Tridentateazolinium Bromides To a solution of 1-alkylimidazoline or 1-alkylbenzimidazole (15 mmol) in DMF (15 mL) was added slowly 2,4,6-tris(bromomethyl)mesitylene (5 mmol) at 25 °C and the resulting mixture was heated for 5 h at 60 °C. Then, Et₂O (15 mL) was added to obtain a white crystalline solid, which was filtered off. The solid was washed with Et₂O (3 × 15 mL), dried under vacuum. The crude product was crystallized from EtOH-Et₂O (2:1).
2,4,6-Tris[3-(2,4,6-trimethylbenzyl)imidazolinium]methyl-mesitylene bromide (2a): yield 4.67 g (93%); mp 86-287 °C. IR: ν_{( CN)} = 1650 cm^-1. ¹H NMR (CDCl₃): δ = 2.16 and 2.22 [s, 27 H, CH₂C₆H₂(CH ₃)₃-2,4,6], 2.49 [s, 9 H, C₆(CH ₃)₃(CH₂)₃-2,4,6], 3.64 and 4.29 [t, J = 10.8, 10.4 Hz, 12 H, NCH₂CH₂N], 4.69 [s, 6 H, C₆(CH₃)₃(CH ₂)₃-2,4,6], 4.91 [s, 6 H, CH ₂C₆H₂(CH₃)₃-2,4,6], 6.76 [s, 6 H, CH₂C₆ H ₂(CH₃)₃-2,4,6], 9.54 (s, 3 H, NCHN). ¹³C{¹H}NMR (CDCl₃): δ = 20.6 and 21.3 [CH₂C₆H₂(CH₃)₃-2,4,6], 18.0 [C₆(CH₃)₃(CH₂)₃-2,4,6], 46.5 [C₆(CH₃)₃(CH₂)₃-2,4,6], 47.9 and 48.0 (NCH₂ CH₂N), 50.3 [CH₂C₆H₂(CH₃)₃-2,4,6], 126.0, 130.1, 138.2 and 139.0 [CH₂ C ₆H₂(CH₃)₃-2,4,6], 129.4, 141.4 and 156.8 [C ₆(CH₃)₃(CH₂)₃-2,4,6], 162.9 (NCHN). Anal. Calcd for C₅₁H₆₉N₆Br₃: C, 60.90; H, 6.91; N, 8.36. Found: C, 60.92; H, 6.88; N, 8.35.
2,4,6-Tris[3-(methoxyethyl)imidazolinium]methyl-mesitylene bromide (2b): yield 3.16 g (81%); mp 156-157 °C. IR: ν_{( CN)} = 1660 cm^-1. ¹H NMR (CDCl₃): δ = 2.44 [s, 9 H, C₆(CH ₃)₃(CH₂)₃-2,4,6], 3.28 (s, 9 H, NCH₂CH₂OCH ₃), 3.41 and 3.52 (t, J = 4.8 Hz, 12 H, NCH ₂CH ₂N), 4.14 (t, J = 11.0 Hz, 6 H, NCH ₂CH₂OCH₃), 4.38 (t, J = 11.2 Hz, 6 H, NCH₂CH ₂OCH₃), 4.65 [s, 6 H, C₆(CH₃)₃(CH ₂)₃-2,4,6], 9.14 (s, 3 H, NCHN). ¹³C{¹H}NMR (CDCl₃): δ = 17.7 [C₆(CH₃)₃(CH₂)₃-2,4,6], 59.0 (NCH₂CH₂OCH₃), 47.7 (NCH₂CH₂OCH₃), 47.9 (NCH₂CH ₂OCH₃), 50.1 and 50.6 (NCH₂ CH₂N), 69.9 [C₆(CH₃)₃(CH₂)₃-2,4,6], 129.1, 141.0 and 157.1 [C ₆(CH₃)₃(CH₂)₃-2,4,6], 162.6 (NCHN). Anal. Calcd for C₃₀H₅₁N₆O₃Br₃: C, 45.99; H, 6.56; N, 10.73. Found: C, 46.00; H, 6.55; N, 10.75.
2,4,6-Tris[3-(ethoxyethyl)imidazolinium]methylmesitylene bromide (2c): yield 3.54 g (86%); mp 123-124 °C. IR: ν_{( CN)} = 1659 cm^-1. ¹H NMR (CDCl₃): δ = 0.96 [t, J = 6.9 Hz, 9 H, NCH₂CH₂OCH₂CH ₃], 2.31 [s, 9 H, C₆(CH ₃)₃(CH₂)₃-2,4,6], 3.30 (q, J = 6.9 Hz, 6 H, NCH₂CH₂OCH ₂CH₃), 3.42 and 3.68 (m, 12 H, NCH ₂CH ₂N), 4.06 (t, J = 10.4 Hz, 6 H, NCH ₂CH₂OCH₂CH₃), 4.25 (t, J = 10.6 Hz, 6 H, NCH₂CH ₂OCH₂CH₃), 4.50 [s, 6 H, C₆(CH₃)₃(CH ₂)₃-2,4,6], 9.03 (s, 3 H, NCHN). ¹³C{¹H}NMR (CDCl₃): δ = 17.5 [C₆(CH₃)₃(CH₂)₃-2,4,6], 15.5 (NCH₂CH₂OCH₂ CH₃), 66.7 (NCH₂CH₂OCH₂CH₃), 47.9 (NCH₂CH₂OCH₂CH₃), 48.4 (NCH₂ CH₂OCH₂CH₃), 50.5 and 50.8 (NCH₂ CH₂N), 68.3 [C₆(CH₃)₃(CH₂)₃-2,4,6], 129.2, 141.2 and 157.2 [C ₆(CH₃)₃(CH₂)₃-2,4,6], 162.7 [NCHN]. Anal. Calcd for C₃₃H₅₇N₆O₃Br_3: C, 48.01; H, 6.96; N, 10.18. Found: C, 48.03; H, 6.99; N: 10.15.
2,4,6-Tris[3-(2,4,6-trimethylbenzyl)benzimida-zolium]methylmesitylene bromide (3a): yield 5.00 g (87%); mp 214-215 °C. IR: ν_{( CN)} = 1562 cm^-1. ¹H NMR (DMSO-d ₆): δ = 2.22 and 2.24 [s, 27 H, CH₂C₆H₂(CH ₃)₃-2,4,6], 2.39 [s, 9 H, C₆(CH ₃)₃(CH₂)₃-2,4,6], 5.94 and 5.95 [s, 12 H, C₆(CH₃)₃(CH ₂)₃-2,4,6 and CH ₂C₆H₂(CH₃)₃-2,4,6 ], 6.93 [s, 6 H, CH₂C₆ H ₂(CH₃)₃-2,4,6], 7.16 [d, J = 8.0 Hz, 3 H, NC₆H₄N], 7.56 and 7.67 (t, J = 7.6 Hz, 6 H, NC₆H₄N), 8.13 (d, J = 8.4 Hz, 3 H, NC₆H₄N), 10.33 (s, 3 H, NCHN). ¹³C{¹H}NMR (DMSO-d ₆): δ = 20.4 and 21.3 [CH₂C₆H₂(CH₃)₃-2,4,6], 17.2 [C₆(CH₃)₃(CH₂)₃-2,4,6], 47.1 [C₆(CH₃)₃(CH₂)₃-2,4,6], 47.4 [CH₂C₆H₂(CH₃)₃-2,4,6], 126.8, 130.4, 138.6 and 139.1 [CH₂ C ₆H₂(CH₃)₃-2,4,6], 129.5, 141.9 and 142.9 [C ₆(CH₃)₃(CH₂)₃-2,4,6], 114.3, 115.2, 127.3, 127.8, 132.1 and 132.4 (NC₆H₄N), 163.1 (NCHN). Anal. Calcd for C₆₃H₆₉N₆Br₃: C, 65.80; H, 6.05; N, 7.31. Found: C, 65.83; H, 6.02; N, 7.30.
2,4,6-Tris[3-(3,4,5-trimethoxybenzyl)benzimida-zolium]methylmesitylene bromide (3b): yield 5.81 g (90%); mp 195-196 °C. IR ν_{( CN)} = 1596 cm^-1. ¹H NMR (CDCl₃): δ = 2.44 [s, 9 H, C₆(CH ₃)₃(CH₂)₃-2,4,6], 3.72 and 3.77 [s, 27 H, CH₂C₆H₂(OCH ₃)₃-3,4,5], 5.84 [s, 6 H, C₆(CH₃)₃(CH ₂)₃-2,4,6], 5.90 [s, 6 H, CH ₂C₆H₂(OCH₃)₃-3,4,5], 6.82 [s, 6 H, CH₂C₆ H ₂(OCH₃)₃-3,4,5], 7.56 (m, 9 H, NC₆H₄N), 8.25 (d, J = 8.1 Hz, 3 H, NC₆H₄N), 10.59 (s, 3 H, NCHN). ¹³C{¹H}NMR (CDCl₃): δ = 18.5 [C₆(CH₃)₃(CH₂)₃-2,4,6], 47.5 [C₆(CH₃)_{3 (} CH₂)₃-2,4,6], 52.7 [CH₂C₆H₂(OCH₃)₃-3,4,5], 57.1 and 61.2 [CH₂C₆H₂(OCH₃)₃-3,4,5], 106.5, 138.6, 141.5 and 153.9 [CH₂ C ₆H₂(OCH₃)₃-3,4,5], 129.2, 142.4 and 142.7 [C ₆(CH₃)₃(CH₂)₃-2,4,6], 114.2, 114.7, 127.5, 127.8, 132.0 and 132.1 (NC₆H₄N), 190.1 (NCHN). Anal. Calcd for C₆₃H₆₉N₆O₉Br₃: C, 58.48; H, 5.37; N, 6.49. Found: C, 58.45; H, 5.36; N, 6.50. 2,4,6-Tris[3-(ethoxtethyl)benzimidazolium]methyl-mesitylene bromide (3c): yield 4.01 g (83%); mp 282-283 °C. IR ν_{( CN)} = 1563 cm^-1. ¹H NMR (CDCl₃): δ = 0.79 (t, J = 6.8 Hz, 9 H, NCH₂CH₂OCH₂CH ₃), 2.48 [s, 9 H, C₆ (CH ₃)₃(CH₂)₃-2,4,6], 3.76 (quart, J = 7.2 Hz, 6 H, NCH₂CH₂OCH ₂CH₃), 3.79 (t, J = 12.0 Hz, 6 H, NCH ₂CH₂OCH₂CH₃), 4.85 (t, J = 12.0 Hz, 6 H, NCH₂CH ₂OCH₂CH₃), 5.90 [s, 6 H, C₆(CH₃)₃(CH ₂)₃-2,4,6], 8.12 (d, J = 7.6 Hz, 3 H, NC₆H₄N), 8.29 (d, J = 8.0 Hz, 3 H, NC₆H₄N), 7.76 (m, 6 H, NC₆H₄N), 10.09 (s, 3 H, NCHN). ¹³C{¹H}NMR (CDCl₃): δ = 17.1 [C₆(CH₃)₃(CH₂)₃-2,4,6], 15.4 (NCH₂CH₂OCH₂ CH₃), 46.7 (NCH₂CH₂OCH₂CH₃), 47.3 (NCH₂ CH₂OCH₂CH₃), 66.2 (NCH₂CH₂OCH₂CH₃), 68.2 [C₆(CH₃)₃(CH₂)₃-2,4,6], 129.4, 142.0 and 142.8 [C ₆(CH₃)₃(CH₂)₃-2,4,6], 114.8, 114.9, 127.4, 127.6, 131.8 and 132.4 (NC₆H₄N), 171.2 (NCHN). Anal. Calcd for C₄₅H₅₇N₆O₃Br₃: C, 55.74; H, 5.92; N, 8.67. Found: C, 55.75; H, 5.90; N: 8.66. General Procedure for the Heck Coupling Reaction Pd(OAc)₂ (1.0 mmol%), 2,4,6-tris[(3-alkyl)azo-linium]methylmesitylene bromide 2 or 3 (0.7 mmol%), aryl bromide (1.0 mmol), styrene (1.5 mmol), t-BuOK (2 mmol), H₂O-DMF (6 mL, 1:1) were added to a small Schlenk tube and the mixture was heated at 50 °C for 5 h. Finally, the mixture was cooled, extracted with EtOAc-hexane (1:5), filtered through a pad of silica gel with copious washings, concentrated and purified by flash chromatography on silica gel. Purity of the compounds was checked by NMR and GC, yields are based on aryl bromide.

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