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

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.

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

References

1a Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 

1b Suzuki A. J. Organomet. Chem.  1999,  576:  147 

1c Stanforth SP. Tetrahedron  1998,  54:  263 

1d Mingji D. Liang B. Wang C. You Z. Xiang J. Dong G. Chen J. Yang Z. Adv. Synth. Catal.  2004,  346:  1669 

2 Miyaura N. Yanagi T. Suzuki A. Synth. Commun.  1981,  11:  513 

3a Wolfe JP. Singer RA. Yang BH. Buchwald SL. J. Am. Chem. Soc.  1999,  121:  9550 

3b Wolfe JP. Buchwald SL. Angew. Chem. Int. Ed.  1999,  38:  2413 

3c Littke AF. Dai C. Fu GC. J. Am. Chem. Soc.  2000,  122:  4020 

4a Zhang C. Huang J. Trudell ML. Nolan SP. J. Org. Chem.  1999,  64:  3804 

4b Böhm VPW. Gstöttmayr CWK. Weskamp T. Herrmann WA. J. Organomet. Chem.  2000,  595:  186 

4c Grasa GA. Viciu MS. Huang J. Zhang C. Trudell ML. Nolan SP. Organometallics  2002,  21:  2866 

4d Singh R. Viciu MS. Kramavera N. Navarro O. Nolan SP. Org. Lett.  2005,  7:  1829 

4e Navarro O. Oonishi Y. Kelly RA. Stevens ED. Briel O. Nolan SP. J. Organomet. Chem.  2004,  689:  3722 

5a Bourissou D. Guerret O. Gabbai FP. Bertrand G. Chem. Rev.  2000,  100:  39 

5b Weskamp T. Böhm VPW. Herrmann WA. J. Organomet. Chem.  2000,  600:  12 

6a Herrmann WA. Angew. Chem. Int. Ed.  2002,  41:  1290 

6b Herrmann WA. Weskamp T. Böhm VPW. Adv. Organomet. Chem.  2001,  46:  181 

6c Herrmann WA. Köcher C. Angew. Chem., Int. Ed. Engl.  1997,  36:  2162 

7 Huang J. Schanz H.-J. Stevens ED. Nolan SP. Organometallics  1999,  18:  2370 

8 Schwarz J. Böhm VPW. Gardiner MG. Grosche M. Herrmann WA. Hieringer W. Raudaschl-Sieber G. Chem.-Eur. J.  2000,  6:  1773 

9 Littke AF. Fu GC. Angew. Chem. Int. Ed.  1998,  37:  3387 

10 Herrmann WA. Böhm VPW. J. Organomet. Chem.  1999,  576:  23 

11a Altenhoff G. Goddard R. Lehmann CW. Glorius F. Angew. Chem. Int. Ed.  2003,  42:  3690 

11b Franki M. Maas G. Schatz J. Eur. J. Org. Chem.  2004,  607 

11c Colacot T. Shea HA. Org. Lett.  2004,  6:  3731 

11d Vargas VC. Rubio RJ. Hollis TK. Salcido ME. Org. Lett.  2003,  5:  4847 

12 Li CJ. Chan TH. Organic Reactions in Aqueous Media   Wiley; New York: 1997. 

13a Genet J.-P. Savignac M. J. Organomet. Chem.  1999,  576:  305 

13b Sakurai H. Tsukuda T. Hirao T. J. Org. Chem.  2002,  67:  2721 

13c Bumagin V. Bykov VV. Tetrahedron  1997,  53:  14437 

13d Parisot S. Kolodziuk R. Henry CG. Iourtchenko A. Sinou D. Tetrahedron Lett.  2002,  43:  7397 

13e LeBlond CR. Andrews AT. Sun Y. Sowa JR. Org. Lett.  2001,  3:  1555 

14 Botella L. Najera C. Angew. Chem. Int. Ed.  2002,  41:  179 

15a Gürbüz N. Özdemir I. Demir S. Çetinkaya B. J. Mol. Catal. A: Chem.  2004,  209:  23 

15b Özdemir I. Çetinkaya B. Demir S. Gürbüz N. Catal. Lett.  2004,  97:  37 

15c Özdemir I. Demir S. Yaºar S. Çetinkaya B. Appl. Organomet. Chem.  2005,  19:  55 

15d Gürbüz N. Özdemir I. Seçkin T. Çetinkaya B. J. Inorg. Organomet. Polym.  2004,  14:  149 

16a Özdemir I. Gök Y. Gürbüz N. Yaºar S. Çetinkaya E. Çetinkaya B. Polish J. Chem.  2004,  78:  2141 

16b Özdemir I. Gök Y. Gürbüz N. Çetinkaya E. Çetinkaya B. Synth. Commun.  2004,  34:  4135 

16c Özdemir I. Gök Y. Gürbüz N. Çetinkaya E. Çetinkaya B. Heteroat. Chem.  2004,  15:  419 

16d Özdemir I. Alici B. Gürbüz N. Çetinkaya E. Çetinkaya B. J. Mol. Catal. A: Chem.  2004,  217:  37 

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.

18 Gök Y. Çetinkaya E. Turk. J. Chem.  2004,  28:  157 

19a Semeril D. Bruneau C. Dixneuf PH. Adv. Synth. Catal.  2002,  344:  585 

19b Semeril D. Cleran MD. Bruneau C. Dixneuf PH. Adv. Synth. Catal.  2001,  343:  184 

19c Castarlenes R. Alaoui-Abdallaoui . Semeril D. Mernari B. Guesmi S. Dixneuf PH. New J. Chem.  2003,  27:  6 

19d Hillier AC. Grasa GA. Viciu MS. Lee HM. Yang C. Nolan SP. J. Organomet. Chem.  2002,  653:  69 

19e Zhang C. Trudell ML. Tetrahedron Lett.  2000,  41:  595