Palladium-Catalyzed Copper-Free Sonogashira Coupling Reaction in Water and Acetone

Abstract

An efficient palladium-catalyzed copper-free Sono­gashira reaction in water and acetone has been developed under mild conditions. The results showed that the aryl iodides could carry out the cross-coupling reaction with a variety of terminal alkynes in high yields in water-acetone in the absence of amine, copper(I) salts, or phosphine ligands at 60 °C for one hour, and good yields were obtained for aryl bromides at 60 °C for 12-24 hours in the presence of triphenylphosphine and piperidine. The method could be used to synthesize polyethynyl aromatic compounds in a one-pot reaction.

copper-free - palladium-catalyzed - Sonogashira coupling - aqueous

References and Notes

1a Viehe HG. Chemistry of Acetylene   Marcel Dekker; New York: 1969.  p.597 

1b Bohlmann F. Burkhart FT. Zero C. Naturally Occurring Acetylenes   Academic Press; London / New York: 1973. 

1c Sonogashira K. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  p.551 

1d Diederich F. Stang PJ. Metal-Catalyzed Cross-Coupling Reactions   Wiley-VCH; Weinheim: 1998. 

1e Miyaura N. Cross-Coupling Reaction   Springer; Berlin: 2002. 

2a Alonso F. Beletskaya IP. Yus M. Chem. Rev.  2004,  104:  3079 

2b Littke AF. Fu GC. Angew. Chem. Int. Ed.  2002,  41:  4176 

2c Tykwinski RR. Angew. Chem. Int. Ed.  2003,  42:  1566 

3a Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  44:  4467 

3b Dieck HA. Heck RF. J. Organomet. Chem.  1975,  93:  259 

3c Cassar L. J. Organomet. Chem.  1975,  93:  253 

4a Thorand S. Krause N. J. Org. Chem.  1998,  63:  8551 

4b Chow H.-F. Wan C.-W. Low K.-H. Yeung Y.-Y. J. Org. Chem.  2001,  66:  1910 

4c Batey RA. Shen M. Lough AJ. Org. Lett.  2002,  4:  1411 

4d Eckhardt M. Fu GC. J. Am. Chem. Soc.  2003,  125:  13642 

4e Novak Z. Szabo A. Repasi J. Kotschy A. J. Org. Chem.  2003,  68:  3327 

4f Garcia D. Cuadro AM. Alvarez-Builla J. Vaquero JJ. Org. Lett.  2004,  6:  4175 

4g Kollhofer A. Plenio H. Adv. Synth. Catal.  2005,  347:  1295 

4h Posset T. Blumel J. J. Am. Chem. Soc.  2006,  128:  8394 

5 Siemsen P. Livingston RC. Diederich F. Angew. Chem. Int. Ed.  2000,  39:  2632 

6a Leadbeater NE. Tominack BJ. Tetrahedron Lett.  2003,  44:  8653 

6b Urgaonkar S. Verkade JG. J. Org. Chem.  2004,  69:  5752 

6c Li J.-H. Liang Y. Xie Y.-X. J. Org. Chem.  2005,  70:  4393 

6d Li J.-H. Zhang X.-D. Xie Y.-X. Synthesis  2005,  804 

6e Liang Y. Xie Y.-X. Li J.-H. J. Org. Chem.  2006,  71:  379 

7a Alonso DA. Najera C. Pacheco MC. Tetrahedron Lett.  2002,  43:  9365 

7b Najera C. Gil-Molto J. Karlstrom S. Falvello LR. Org. Lett.  2003,  5:  1451 

7c Méry D. Heuzé K. Astruc D. Chem. Commun.  2003,  1934 

7d Heuze K. Mery D. Gauss D. Astruc D. Chem. Commun.  2003,  2274 

7e Arques A. Auñon D. Molina P. Tetrahedron Lett.  2004,  45:  4337 

7f Alonso DA. Botella L. Najera C. Pacheco MC. Synthesis  2004,  1713 

7g Heuze K. Mery D. Gauss D. Blais JC. Astruc D. Chem. Eur. J.  2004,  10:  3936 

8a Mori A. Kawashima J. Shimada T. Suguro M. Org. Lett.  2000,  2:  2935 

8b Eberhard MR. Wang Z. Jensen CM. Chem. Commun.  2002,  818 

8c Sakai N. Annaka K. Konakahara T. Org. Lett.  2004,  6:  1527 

9a Fukuyama T. Shinmen M. Nishitani S. Sato M. Ryu I. Org. Lett.  2002,  4:  1691 

9b Park SB. Alper H. Chem. Commun.  2004,  1306 

9c Gholap AR. Venkatesan K. Pasricha R. Daniel T. Lahoti RJ. Srinivasan KV. J. Org. Chem.  2005,  70:  4869 

10a Djakovitch L. Rollet P. Adv. Synth. Catal.  2004,  346:  1782 

10b Rollet P. Kleist W. Dufaud V. Djakovitch L. J. Mol. Catal. A: Chem.  2005,  241:  39 

10c Li P. Wang L. Adv. Synth. Catal.  2006,  348:  681 

10d Elizabeth T. Ali A. Julien M. Synlett  2005,  487 

10e Cwik A. Hell Z. Figueras F. Tetrahedron Lett.  2006,  47:  3023 

11a Böhm VPW. Herrmann WA. Eur. J. Org. Chem.  2000,  3679 

11b Kollhofer A. Pullmann T. Plenio H. Angew. Chem. Int. Ed.  2003,  42:  1056 

11c Gelman D. Buchwald SL. Angew. Chem. Int. Ed.  2003,  42:  5993 

11d Soheili A. Albaneze-Walker J. Murry JA. Dormer PG. Hughes DL. Org. Lett.  2003,  5:  4191 

11e Ma Y. Song C. Jiang W. Wu Q. Wang Y. Liu X. Andrus MB. Org. Lett.  2003,  5:  3317 

11f Cheng J. Sun Y. Wang F. Guo M. Xu J.-H. Pan Y. Zhang Z. J. Org. Chem.  2004,  69:  5428 

12a Li C.-J. Chan T.-H. Organic Reactions in Aqueous Media   Wiley; New York: 1997. 

12b Organic Synthesis in Water   Grieco PA. Academic Press; Dordrecht: 1997. 

12c Aqueous-Phase Organometallic Catalysis   2nd ed:  Cornils B. Herrmann WA. Wiley-VCH; Weinheim: 2004. 

12d Leadbeater NE. Chem. Commun.  2005,  2881 

12e Li C.-J. Chem. Rev.  2005,  105:  3095 

13a Casalnuovo AL. Calabrese JC. J. Am. Chem. Soc.  1990,  112:  4324 

13b Dibowski H. Schmidtchen FP. Tetrahedron Lett.  1998,  39:  525 

13c Novak Z. Szabo A. Repasi J. Kotschy A. J. Org. Chem.  2003,  68:  3327 

13d Djakovitch L. Rollet P. Tetrahedron Lett.  2004,  45:  1367 

13e Bhattacharyaa S. Sengupta S. Tetrahedron Lett.  2004,  45:  8733 

13f Wolf C. Lerebours R. Org. Biomol. Chem.  2004,  2:  2161 

13g Gelman D. Buchwald SL. Angew. Chem. Int. Ed.  2005,  44:  6173 

13h Liang B. Dai M. Chen J. Yang Z. J. Org. Chem.  2005,  70:  391 

13i Zhang G. Synlett  2005,  619 

14a Liu L. Zhang Y. Wang Y. J. Org. Chem.  2005,  70:  6122 

14b Liu L. Zhang Y. Xin B. J. Org. Chem.  2006,  71:  3994 

14c Xin B. Zhang Y. Liu L. Wang Y. Synlett  2005,  3083 

14d Xin B. Zhang Y. Cheng K. J. Org. Chem.  2006,  71:  5725 

15

General Procedure for the Sonogashira Reaction of Aryl Iodides
A mixture of NaOH (0.08 g, 2 mmol), Pd(OAc)₂ (2 mg, 1 mol%), distilled H₂O (3 g), and acetone (3 g, 3.8 mL) was stirred for 5 min. Then, aryl iodides (1 mmol) and terminal alkynes (1.2 mmol) were introduced and the mixture of the reaction was heated to 60 °C for 1 h. Afterward, the reaction solution was cooled to r.t. and extracted four times with Et₂O (4 × 10 mL). The combined organic phase was analyzed by GC and GC-MS. Further purification of the product was achieved by flash chromatography on a silica gel column.
1-(2-Phenylethynyl)naphthalene (Table [2] , entry 6): ¹H NMR (500 MHz, CDCl₃, TMS): δ = 8.43-8.45 (d, 1 H, J = 8.35 Hz), 7.72-7.80 (m, 3 H), 7.61-7.63 (m, 2 H), 7.55 (m, 1 H), 7.46-7.48 (m, 1 H), 7.33-7.38 (m, 1 H), 7.30-7.32 (m, 3 H). MS (EI): m/z (%) = 229 (20) [M⁺ + 1], 228 (100) [M⁺], 226 (43).

16

General Procedure for the Sonogashira Reaction of Aryl Bromides and Polyhaloaryls
A mixture of piperidine (0.17 g, 2 mmol; for dihalides, 4 mmol; for trihalides, 6 mmol; for tetrahalides, 8 mmol), PdCl₂ (11 mg, 5 mol%; for dihalides, PdCl₂ = 10 mol%; for trihalides, PdCl₂ = 15 mol%; for tetrahalides, PdCl₂ = 20 mol%), PPh₃ (26 mg, 10 mol%; for dihalides, PPh₃ = 20 mol%; for trihalides, PPh₃ = 30 mol%; for tetrahalides, PPh₃ = 40 mol%), distilled H₂O (3 g), and acetone (3 g, 3.8 mL) was stirred for 5 min under nitrogen. Then, aryl bromides or polyhaloaryls (1 mmol) and terminal alkynes (1.2 mmol; for dihalides, alkynes = 2.4 mmol; for trihalides, alkynes = 3.6 mmol; for tetrahalides, alkynes = 4.8 mmol) were introduced and the mixture of the reaction was heated to 60 °C for the indicated time under nitrogen. Afterwards, the reaction solution was cooled to r.t. and extracted with Et₂O (4 × 10 mL). The combined organic phase was analyzed by GC and GC-MS. Further purification of the product was achieved by flash chromatography on a silica gel column.
1,4-Bis(2-phenylethynyl)benzene (Table [4] , entry 1): ¹H NMR (500 MHz, CDCl₃, TMS): δ = 7.52-7.54 (m, 4 H), 7.50 (s, 4 H), 7.34-7.36 (m, 6 H). MS (EI): m/z (%) = 279 (25) [M⁺ + 1], 278 (100) [M⁺], 139 (10).

17a Yamaguchi Y. Kobayashi S. Miyamura S. Okamoto Y. Wakamiya T. Matsubara Y. Yoshida Z. Angew. Chem. Int. Ed.  2004,  43:  366 

17b Yamaguchi Y. Ochi T. Miyamura S. Tanaka T. Kobayashi S. Wakamiya T. Matsubara Y. Yoshida Z.-I. J. Am. Chem. Soc.  2006,  128:  4504