Ligand-Free Copper-Catalyzed Cross-Coupling Reaction of Alkynes with Aryl Iodides and Vinyl Halides

Abstract

A copper-catalyzed cross-coupling reaction of alkynes with aryl iodides is described. The system tolerates a broad range of functional groups and enables the sterically demanding substrates presented during the catalysis with only 5–10 mol% of Cu₂O as the catalyst.

Key words

copper - cross-coupling - Sonogashira reaction - ligand-free - aryl iodide - vinyl halide

• References and Notes

• 1a Nicolaou KC, Dai W.-M. Angew. Chem., Int. Ed. Engl. 1991; 30: 1387
• 1b Grissom JW, Gunawardena GU, Klingberg D, Huang D. Tetrahedron 1996; 52: 6453
• 2 Sonogashira K In Handbook of Organopalladium Chemistry for Organic Synthesis . Negishi E. Wiley-Interscience; New York: 2002: 493-529
• 3a de Haro T, Nevado C. J. Am. Chem. Soc. 2010; 132: 1512
• 3b Panda B, Sarkar TK. Tetrahedron Lett. 2010; 51: 301
• 3c Carril M, Correa A, Bolm C. Angew. Chem. Int. Ed. 2008; 47: 4862

For reviews, see:
• 4a Heravi MM, Sadjadi S. Tetrahedron 2009; 65: 7761
• 4b Chinchilla R, Nájera C. Chem. Rev. 2007; 107: 874
• 4c Doucet H, Hierso J.-C. Angew. Chem. Int. Ed. 2007; 46: 834
• 4d Nicolaou KC, Bulger PG, Sarlah D. Angew. Chem. Int. Ed. 2005; 44: 4442
• 4e Negishi E, Anastasia L. Chem. Rev. 2003; 103: 1979
• 4f Littke AF, Fu GC. Angew. Chem. Int. Ed. 2002; 41: 4176
• 4g Siemsen P, Livingston RC, Diederich F. Angew. Chem. Int. Ed. 2000; 39: 2632
• 4h Martin RE, Diederich F. Angew. Chem. Int. Ed. 1999; 38: 1350
• 5 Okuro K, Furuune M, Enna M, Miura M, Nomura M. J. Org. Chem. 1993; 58: 4716
• 6 Gujadhur RK, Bates CG, Venkataraman D. Org. Lett. 2001; 3: 4315
• 7 Saejueng P, Bates CG, Venkataraman D. Synthesis 2005; 1706
• 8 Ma D, Liu F. Chem. Commun. 2004; 1934
• 9 Wang YF, Deng W, Liu L, Guo QX. Chin. Chem. Lett. 2005; 16: 1197
• 10 Li J.-H, Li J.-L, Wang D.-P, Pi S.-F, Xie Y.-X, Zhang M.-B, Hu X.-C. J. Org. Chem. 2007; 72: 2053
• 11 Xie Y.-X, Deng C.-L, Pi S.-F, Li J.-H, Yin D.-L. Chin. J. Chem. 2006; 24: 1290
• 12 Monnier F, Turtaut F, Duroure L, Taillefer M. Org. Lett. 2008; 10: 3203
• 13 Zuidema E, Bolm C. Chem. Eur. J. 2010; 16: 4181

For more selected examples, see:
• 14a Hosseinzadeh R, Mohadjerani M, Tavakoli R. Synth. Commun. 2010; 40: 282
• 14b Thakur KG, Jaseer EA, Naidu AB, Sekar G. Tetrahedron Lett. 2009; 50: 2865
• 14c Guan JT, Yu G.-A, Chen L, Weng TQ, Yuan JJ, Liu SH. Appl. Organomet. Chem. 2009; 23: 75
• 14d Mao J, Guo J, Ji S.-J. J. Mol. Catal. A: Chem. 2008; 284: 85
• 14e Tang B.-X, Wang F, Li J.-H, Xie Y.-X, Zhang M.-B. J. Org. Chem. 2007; 72: 6294
• 14f Colacino E, Daïch L, Martinez J, Lamaty F. Synlett 2007; 1279
• 14g Thathagar MB, Beckers J, Rothenberg G. Green Chem. 2004; 6: 215
• 14h Liu Y, Yang J, Bao W. Eur. J. Org. Chem. 2009; 5317
• 14i Xie X, Xu XB, Li HF, Xu XL, Yang JY, Li YZ. Adv. Synth. Catal. 2009; 351: 1263
• 14j Wu M, Mao J, Guo J, Ji S. Eur. J. Org. Chem. 2008; 4050
• 14k Bates CG, Saejueng P, Venkataraman D. Org. Lett. 2004; 6: 1441
• 14l Okuro K, Furuune M, Enna M, Miura M, Nomura M. J. Org. Chem. 1993; 58: 4716
• 14m Okuro K, Furuune M, Miura M, Nomura M. Tetrahedron Lett. 1992; 33: 5363
• 15 Mao J, Xie G, Wu M, Guo J, Jia S. Adv. Synth. Catal. 2008; 350: 2477
• 16 Thathagar MB, Beckers J, Rothenberg G. Green Chem. 2004; 6: 215
• 17 Biffis A, Scattolin E, Ravasio N, Zaccheria F. Tetrahedron Lett. 2007; 48: 8761
• 18 Yuan Y, Zhu H, Zhao D, Zhang L. Synthesis 2011; 1792
• 19 Gonda Z, Tolnai GL, Novák Z. Chem. Eur. J. 2010; 16: 11822
• 20 Zou L.-H, Johansson AJ, Zuidema E, Bolm C. Chem. Eur. J. 2013; 19: 8144
• 21 Li T, Qu X, Xie G, Mao J. Chem. Asian J. 2011; 6: 1325
• 22a Tsai W.-T, Lin Y.-Y, Wang Y.-J, Lee C.-F. Synthesis 2012; 44: 1507
• 22b Lin Y.-Y, Wang Y.-J, Cheng J.-H, Lee C.-F. Synlett 2012; 23: 930
• 22c Lin C.-H, Wang Y.-J, Lee C.-F. Eur. J. Org. Chem. 2010; 4368
• 23 ICP-MS analysis showed 2 ppb of palladium in Cu₂O; no palladium has been detected in Cs₂CO₃ and phenylacetylene.
• 24 General Procedure for the Synthesis of Compounds 3a–e A sealable vial equipped with a magnetic stir bar was charged with Cs₂CO₃ (652 mg, 2.0 mmol) and Cu₂O (7.0 mg, 0.05 mmol) under a nitrogen atmosphere. The aperture of the vial was then covered with a rubber septum. Under a nitrogen atmosphere, aryl alkyne 1 (1.5 mmol), aryl iodide 2 (1.0 mmol), and DMF (0.5 mL) were added by syringe. The septum was then replaced by a screw cap containing a Teflon-coated septum, and the reaction vessel was placed at 135 °C. After stirring at this temperature for 24 h, the heterogeneous mixture was cooled to r.t. and diluted with EtOAc (20 mL). The resulting solution was filtered through a pad of silica gel, then washed with EtOAc (20 mL), and concentrated to give the crude material which was then purified by column chromatography on silica gel to yield alkyne 3. Data for Five Representative Examples Diphenylacetylene (3a)²⁵ Following the general procedure, using Cs₂CO₃ (652 mg, 2.0 mmol) and Cu₂O (7.0 mg, 0.05 mmol) in DMF (0.5 mL), then purified by column chromatography (SiO₂, hexane) to provide 3a as a white solid (168 mg, 94% yield); mp 58–59 °C (lit.²⁵ 60–61 °C). ¹H NMR (400 MHz, CDCl₃): δ = 7.26–7.41 (m, 6 H), 7.56–7.60 (m, 4 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 89.4, 123.2, 128.2, 128.3, 131.6 ppm. Phenyl-p-tolylacetylene (3b)²⁵ Following the general procedure, using phenylacetylene (0.0167 mL, 1.5 mmol) and 4-iodotoluene (218 mg, 1.0 mmol), then purified by column chromatography (SiO₂, hexane) to provide 3b as a white solid (181 mg, 94% yield); mp 69–70 °C (lit.²⁵ 71–72.5 °C). ¹H NMR (400 MHz, CDCl₃): δ = 2.17 (s, 3 H), 6.96–6.97 (m, 1 H), 6.14–6.16 (m, 2 H), 7.28–7.38 (m, 2 H), 7.37–7.39 (m, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 21.5, 88.7, 89.5, 120.1, 123.4, 128.0, 128.3, 129.1, 131.5, 131.5, 138.4 ppm. 4-(Phenylethynyl)aniline (3c)^19c Following the general procedure, using phenylacetylene (0.167 mL, 1.5 mmol) and 4-iodoaniline (218 mg, 1.0 mmol), then purified by column chromatography (SiO₂, hexane–EtOAc = 9:1) provide 3c as a brown solid (166 mg, 86% yield); mp 123–124 °C (lit.^19c 126–127 °C). ¹H NMR (400 MHz, CDCl₃): δ = 3.75 (br s, 2 H), 6.57 (d, J = 8.0 Hz, 2 H), 7.28–7.33 (m, 5 H), 7.48–7.50 (m, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 87.3, 90.1, 112.5, 114.7, 123.8, 127.6, 128.2, 131.3, 132.9, 146.6 ppm. (4-Methoxyphenyl)phenylacetylene (3d)²⁵ Following the general procedure, using phenylacetylene (0.083 mL, 0.75 mmol) and 4-iodoanisole (120 mg, 0.5 mmol), then purified by column chromatography (SiO₂, hexane–EtOAc = 10:1) to provide 3d as a white solid (92 mg, 88% yield); mp 55–57 °C (lit.²⁵ 58–60 °C). ¹H NMR (400 MHz, CDCl₃): δ = 3.75 (s, 3 H), 6.83–6.85 (m, 2 H), 7.28–7.31 (m, 3 H), 7.44–7.52 (m, 4 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 55.1, 88.0, 89.4, 113.9, 115.3, 123.5, 127.9, 128.2, 131.4, 133.0, 159.6 ppm. 2-(Phenylethynyl)anisole (3e)^19c Following the general procedure, using phenylacetylene (0.167 mL, 1.5 mmol) and 2-iodoanisole (0.130 mL, 1.0 mmol), then purified by column chromatography (SiO₂, hexane–EtOAc = 9:1) to provide 3e as a yellow oil (132 mg, 64% yield). ¹H NMR (400 MHz, CDCl₃): δ = 3.86 (s, 3 H), 6.84–6.93 (m, 2 H), 7.24–7.33 (m, 4 H), 7.48–7.50 (m, 1 H), 7.54–7.57 (m, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 55.7, 85.7, 93.3, 110.6, 112.3, 120.4, 123.5, 128.0, 128.2, 129.7, 131.5, 133.5, 159.9 ppm.
• 25 Li P, Wang L, Li H. Tetrahedron 2005; 61: 8633