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Synlett 2005(15): 2394-2396  
DOI: 10.1055/s-2005-872673
LETTER
© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalyzed Suzuki-Miyaura Reaction of Aryl Chlorides in Aqueous Media Using Tetrahydrodiazepinium Salts as Carbene Ligands

Ismail Özdemir*a, Nevin Gürbüza, Yetkin Göka, Engin Çetinkayab, Bekir Çetinkayab
a Inönü University, Faculty of Science and Arts, Chemistry Department, 44280 Malatya, Turkey
Fax: +90(422)3410212; e-Mail: iozdemir@inonu.edu.tr;
b Department of Chemistry, Ege University, 35100 Bornova-Izmir, Turkey
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Publication History

Received 13 June 2005
Publication Date:
07 September 2005 (online)

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Abstract

A highly effective, easy to handle, and environmentally benign process for palladium-mediated Suzuki cross-coupling was developed. The in situ prepared three-component system of Pd(OAc)2, 1,3-dialkyltetrahydrodiazepinium chlorides (2a-e), and K2CO3 catalyzes quantitatively the Suzuki-Miyaura cross-coupling of deactivated aryl chloride.

Key words

tetrahydrodiazepinium - Suzuki-Miyaura reaction - ­palladium - C-C coupling - N-heterocyclic carbene

17

General procedure for the synthesis of 1,3-dialkyl-4,5,6,7-tetrahydro-1,3-diazepinium chloride ( 2): To a solution of 1,4-bis(alkylamino)butane (1 mmol) in CH(OEt)3 (30 mL), NH4Cl (1 mmol) was added; the reaction mixture was heated for 18 h at 100 °C. A white solid was precipitated. The precipitate was then crystallized from EtOH-Et2O (1:2).
1,3-Bis(2,4,6-trimethylbenzyl)-4,5,6,7-tetrahydro-1,3-diazepinium chloride ( 2a). Yield: 2.20 g (73%); mp 217-218 °C. 1H NMR (300.13 MHz, DMSO): δ = 1.90 (quintet, J = 7.2 Hz, 4 H, NCH2CH 2CH 2CH2N), 2.09 and 2.23 [s, 18 H, 2,4,6-(CH 3)3C6H2CH2], 3.66 (t, J = 7.2 Hz, 4 H, NCH 2CH2CH2CH 2N), 4.58 [s, 4 H, 2,4,6-(CH3)3C6H2CH 2], 6.77 [s, 4 H, 2,4,6-(CH3)3C6 H 2CH2], 7.30 (s, 1 H, 2-CH). 13C{1H} NMR (75.47 MHz, DMSO): δ = 19.8, 49.9 (NCH2 CH2 CH2 CH2N), 21.3, 24.9 [2,4,6-(CH3)3C6H2CH2], 54.3 [2,4,6-(CH3)3C6H2 CH2], 126.7, 129.9, 138.6, 138.9 [2,4,6-(CH3)3 C 6H2CH2], 154.5 (2-CH). Anal. Calcd for C25H35N2Cl: C, 75.25; H, 8.84; N, 7.02. Found: C, 75.23; H, 8.85; N, 7.04.
1,3-Bis(2,4,6-trimethoxybenzyl)-4,5,6,7-tetrahydro-1,3-diazepinium chloride ( 2b). Yield: 1.48 g (90%); mp 233-234 °C. 1H NMR (300.13 MHz, DMSO): δ = 1.66 (quintet, J = 7.2 Hz, 4 H, NCH2CH 2CH 2CH2N), 3.55 and 3.67 [s, 18 H, 2,4,6-(CH 3O)3C6H2CH2], 3.46 (t, J = 7.2 Hz, 4 H, NCH 2CH2CH2CH 2N), 4.50 [s, 4 H, 2,4,6-(CH3O)3C6H2CH 2], 6.02 [s, 4 H, 2,4,6-(CH3O)3C6 H 2CH2], 6.92 (s, 1 H, 2-CH). 13C{1H} NMR (75.47 MHz, DMSO): δ = 25.8, 50.2 (NCH2 CH2 CH2 CH2N), 51.3, 56.9 [2,4,6-(CH3O)3C6H2CH2], 57.3 [2,4,6-(CH3O)3C6H2 CH2], 92.3, 103.4, 156.3, 160.9 [2,4,6-(CH3O)3 C 6H2CH2], 163.4 (2-CH). Anal. Calcd for C25H35N2O6Cl: C, 60.66; H, 7.12; N, 5.65. Found: C, 60.68; H, 7.10; N, 5.67.
1,3-Bis(3,4,5-trimethoxybenzyl)-4,5,6,7-tetrahydro-1,3-diazepinium chloride ( 2c). Yield: 1.23 g (87%); mp 151-152 °C. 1H NMR (300.13 MHz, DMSO): δ = 1.78 (quintet, J = 7.2 Hz, 4 H, NCH2CH 2CH 2CH2N), 3.34 (t, J = 7.2 Hz, 4 H, NCH 2CH2CH2CH 2N), 3.65 and 3.78 [s, 18 H, 3,4,5-(CH 3O)3C6H2CH2], 4.64 [s, 4 H, 3,4,5-(CH3O)3C6H2CH 2], 6.88 [s, 4 H, 3,4,5-(CH3O)3C6 H 2CH2], 9.11 (s, 1 H, 2-CH). 13C{1H} NMR (75.47 MHz, DMSO): δ = 25.0, 48.9 (NCH2 CH2 CH2 CH2N), 56.8, 60.7 [3,4,5-(CH3O)3C6H2CH2], 60.3 [3,4,5-(CH3O)3C6H2 CH2], 106.9, 131.4, 138.3, 153.8 [3,4,5-(CH3O)3 C 6H2CH2], 159.5 (2-CH). Anal. Calcd for C25H35N2O6Cl: C, 60.66; H, 7.12; N, 5.65. Found: C, 60.67; H, 7.11; N, 5.64.
1,3-Bis( p -methoxybenzyl)-4,5,6,7-tetrahydro-1,3-diazepinium chloride ( 2d). Yield: 1.82 g (79%); mp 298-299 °C. 1H NMR (300.13 MHz, DMSO): δ = 1.71 (quintet, J = 6.8 Hz, 4 H, NCH2CH 2CH 2CH2N), 3.01 (t, J = 6.8 Hz, 4 H, NCH 2CH2CH2CH 2N), 3.81 (s, 6 H, p-CH 3OC6H4CH2), 4.64 (s, 4 H, p-CH3OC6H4CH 2), 7.01 and 7.39 (d, J = 8.4 Hz, 8 H, p-CH3OC6 H 4CH2), 8.89 (s, 1 H, 2-CH). 13C{1H} NMR (75.47 MHz, DMSO): δ = 23.1, 46.3 (NCH2 CH2 CH2 CH2N), 50.7 (p-CH3OC6H4CH2), 55.8 (p-CH3OC6H4 CH2), 115.0, 123.5, 131.9 (p-CH3OC6H4CH2), 160.2 (2-CH). Anal. Calcd for C21H27N2O2Cl: C, 67.27; H, 7.25; N, 7.47. Found: C, 67.30; H, 7.23; N, 7.46.
1,3-Bis( p -dimethylaminobenzyl)-4,5,6,7-tetrahydro-1,3-diazepinium chloride ( 2e). Yield: 3.11 g (92%), mp 247-248 °C. 1H NMR (300.13 MHz, DMSO): δ = 1.68 (quintet, J = 6.8 Hz, 4 H, NCH2CH 2CH 2CH2N), 2.89 [s, 12 H, p-(CH 3)2NC6H4CH2], 3.52 (t, J = 6.8 Hz, 4 H, NCH 2CH2CH2CH 2N), 4.54 [s, 4 H, p-(CH3)2NC6H4CH 2], 6.73 and 7.27 (d, J = 8.4 Hz, 8 H, p-(CH3)2NC6 H 4CH2), 8.87 (s, 1 H, 2-CH). 13C{1H} NMR (75.47 MHz, DMSO): δ = 24.7, 48.5 (NCH2 CH2 CH2 CH2N), 40.7 [p-(CH3)2NC6H4CH2], 60.1 [p-(CH3)2NC6H4 CH2], 112.9, 122.2, 130.1, 151.1 [p-(CH3)2NC 6H4CH2], 158.3 (2-CH). Anal. Calcd for C23H33N4Cl: C, 68.89; H, 8.29; N, 13.97. Found: C, 68.88; H, 8.30; N, 13.97.
General procedure for the Suzuki-Miyaura coupling reaction Pd(OAc)2 (1.0 mmol%), 1,3-dialkyltetrahydrodiazepinium chlorides, 2 (2.0 mmol%), aryl chloride (1.0 mmol), phenylboronic acid (1.2 mmol), K2CO3 (2 mmol), H2O-DMF (6 mL, 1:1) were added to a small Schlenk tube in air and the mixture was heated at 60 °C for 0.5 h. At the conclusion of the reaction, the mixture was cooled, extracted with Et2O, filtered through a pad of silica gel, washed thoroughly, concentrated, and purified by flash chromatography on silica gel. The purity of the compounds was checked by GC and yields are based on aryl chloride.