Green and Sustainable Chemistry
Vol.3 No.1(2013), Article ID:28060,4 pages DOI:10.4236/gsc.2013.31003

Carbonylative Coupling of 4,4’-Diiodobiphenyl Catalyzed by Pd(NHC) Complex

Do-Hun Lee1*, Jung-Tai Hahn2, Dai-Il Jung1*

1Department of Chemistry, Dong-A University, Busan, South Korea

2Department of Beautycare, Youngdong University, Youngdong, South Korea

Email: *,

Received September 22, 2012; revised November 3, 2012; accepted November 15, 2012

Keywords: Carbonylative Coupling; Metal Carbonyl; Pd(NHC) Complex; 4,4’-Diiodobiphenyl; Phenylboronic Acid


To develop a luminescent material with high color purity, luminous efficiency, and stability, we synthesized diketone by carbonylative Suzuki coupling in the presence of Pd(NHC) complex as the catalyst. Carbonylative coupling of 4,4’-diiodobiphenyl and phenylboronic acid was investigated to study in detail the catalytic ability of the Pd(NHC) complex. Reactions were carried out using both CO and metal carbonyls. Bis-(1,3-dihydro-1,3-dimethyl-2H-imidazol- 2-ylidene) diiodo palladium was used as the catalytic complex. Reaction products biphenyl-4,4’-diylbis (phenylmethanone) 3 and (4’-iodobiphenyl-4-yl)(phenyl) methanone 4 were obtained as a result of CO insertion into the palladium(II)-aryl bond. However, when pyridine-4-yl boronic acid was used in place of phenylboronic acid as the starting reagent, synthetic reaction yielding 3 and 4 were found not to occur.

1. Introduction

Aryl ketones and flavanoids are common scaffolds in many natural products and biologically active small molecules [1-7]. A carbonylative coupling method for the synthesis of aryl compounds with CO was pioneered by Heck [8-11]. This method is one of the most efficient and direct routes to synthesize aryl ketones as it forms tow carbon-carbon bonds in a single step, in contrast to the conventional method of introducing ketone functional group in a stepwise fashion. Carbonylative coupling has since been further developed to synthesize a range of carbon nucleophiles [12], including those of tin [13-17], copper [18-22], boron [23-25], zinc [26], aluminum [27], magnesium [28], and silicon [29-31]. Our purpose is to synthesize a new distyryl biphenyl arylene (DBA) derivative as a blue-emitting material. To develop such a luminescent material with high color purity, luminous efficiency, and stability, first of all, we synthesized diketone with Pd(NHC) complex as a catalyst under a balloon of CO or metal carbonyl.

During the course of an on-going synthetic project for preparing aryl ketones, we decided to evaluate the applicability of N-heterocyclic carbene (NHC) ligands. NHC ligands have gained popularity in metal-catalyzed crosscoupling reactions for several reasons [32-35]: 1) the steric bulk that they introduce around the metal center facilitates reductive elimination; 2) their strong σ-donating character enables facile oxidative addition; and 3) their greater stability at elevated temperatures relative to phosphineligands enables their use under a broader range of reaction conditions. Carbonylative Suzuki coupling using the synthesized NHC-Pd complex was carried out under a balloon of CO or metal carbonyls. To study the scope of the process, the reaction conditions were optimizied for the cross-coupling of 4,4’-diiodobiphenyl and phenylboronic acid with N-heterocyclic carbene (NHC) ligand under a balloon (1 atm) of CO or metal carbonyls. 4,4’-diiodobiphenyl 1) and phenylboronic acid 2) were reacted under CO (1 bar, a balloon) atmosphere in the presence of the Pd(NHC) complex catalyst formed in situ [36,37].

2. Experimental

2.1. Carbonylative Coupling Reaction under Carbon Monoxide

In a typical reaction, Pd(NHC) complex (2 × 10−3 g, 5 × 10−2 mol) was dissolved in 15 mL anisole under N2 gas. After the formation of a pale brown homogeneous solution, phenylboronic acid (0.112 g, 1 × 10−3 mol), 4,4’- diiodobiphenyl (0.203 g, 5 × 10−4 mol), and potassium carbonate (0.425 g, 1.5 × 10−3 mol) were added. The atmosphere was changed to carbon monoxide and the reaction mixture was kept at 80˚C for 24 h. After elimination of Pd(NHC) complex by filteration, the reaction mixture was diluted water (10 mL) and CH2Cl2 (20 mL). The neutralized solution was extracted with CH2Cl2. The organic layer was dried (Na2SO4), filtered, and concentrated. The reaction mixture was analyzed immediately by GC-MS. The residue was chromatographed on a silica gel (n-hexane:ethylacetate = 20:1, v/v) yield 3 (0.154 g, 42.6%) and 4 (4.9 × 10−2 g, 12.7%).

2.2. Carbonylative Coupling Reaction under Metal Carbonyl

The mixture of 4,4’-diiodobiphenyl (0.203 g, 5 × 10−4 mol), phenylboronic acid (0.112 g, 1 × 103 mol), K2CO3 (0.425 g, 1.5 × 10−3 mol) and Di-(1,3-dihydro-1,3-dimethyl-2H-imidazol-2-ylidene)diiodopalladium (2 × 10−3 g, 5 × 10−2 mol) and Molybdenum hexacarbonyl (9.2 × 10−2 mol, 0.7 eq) was stirred in 15 mL anisole under N2. The reaction mixture was kept at 80˚C for 24 h. After elimination of Pd(NHC) complex by filteration, the reaction mixture was diluted water (10 mL) and CH2Cl2 (20 mL). The neutralized solution was extracted with CH2Cl2. The organic layer was dried (Na2SO4), filtered, and concentrated. The reaction mixture was analyzed immediately by GC-MS. The residue was chromatographed on a silica gel (n-hexane:ethylacetate = 20:1, v/v) yield 3 (0.189 g, 52.3%) and 4 (5.2 × 10−2 g, 13.5%).

2.3. Synthesis of Bis-(1,3-dihydro-1,3-dimethyl- 2H-imidazol-2-ylidene) diiodopalladium

The synthetic scheme for producing bis-(1,3-dihydro-1,3- dimethyl-2H-imidazol-2-ylidene) diiodopalladium catalyst is as follows:

N,N’-dimethyl imidazolium iodide was obtained by the reaction of N-methylimidazole with methyl iodide. Following this, reaction of N,N’-dimethyl imidazolium iodide with palladium acetate resulted in NHC-Pd complex in good yield (72%).

3. Results and Discussion

The desired carbonylative products biphenyl-4,4’-diylbis (phenyl-methanone) 3 and (4’-iodobiphenyl-4-yl)(phenyl) methanone 4 were formed in all cases, irrespective of the reaction conditions.

When metal carbonyl [for Mo(CO)6: 3 = 42.6% and 4 = 12.7%; Mn2(CO)10: 3 = 6.6% and 4 = 33.1%; Co2(CO)8: 3 = 48.6% and 4 = 11.2%; Fe3(CO)12: 3 = 9.9% and 4 = 24.8%; Fe(CO)5: 3 = 62.5% and 4 = 10.6%] was used in place of CO, we achieved the same reaction products.

In reactions with Mn2(CO)10 and Fe3(CO)12 as metal carbonyals, yield of 4 was higher then that of 3. As seen in Table 1, various metal carbonyls were as effective as CO donors as CO itself. The plausible mechanism of diketone formation is assumed to be as shown in Scheme 1.

4. Conclusions

When metal carbonyl was used in place of CO, we achieved the same reaction products.

We assume that the two reactions needed to obtain 3 require a longer reaction time as 4 is formed as a reaction intermediate. When pyridine-4-ylboronic acid is used in place of phenylboronic acid,

carbonylative Suzuki coupling under CO or metal carbonyls [Mo(CO)6, Mn2(CO)10, Co2(CO)8, Fe3(CO)12, and Fe(CO)5] is found not to occur. In future, we intend to

Table 1. Carbonylative Suzuki coupling with phenylboronic acid and 4,4’-diiodobiphenyl.

Scheme 1. Simplified catalytic cycle showing the formation of 3.

synthesize various diketones by using heteroaromatic boronic acid to develop a luminescent material.

5. Acknowledgements

The work was supported by a grant of Dong-A University (2012).


  1. Y. Jiang and P. Tu, “Four New Phenones from the Cortexes of Polygalatenuifolia,” Chemical & Pharmaceutical Bulletin, Vol. 53, No. 9, 2005, pp. 1164-1166. doi:10.1248/cpb.53.1164
  2. Nilar, L.-H. D. Nguyen, G. Venkatraman, K.-Y. Sim and L. J. Harrison, “Xanthones and Benzophenones from Garciniagriffithii and Garcinia mangostana,” Phytochemistry, Vol. 66, No. 14, 2005, pp. 1718-1723. doi:10.1016/j.phytochem.2005.04.032
  3. J. W. Lampe, C. K. Biggers, J. M. Defauw, R. J. Foglesong, S. E. Hall, J. M. Heerding, S. P. Hollinshead, H. Hu, P. F. Hughes, G. E. Jagdmann Jr., M. G. Johnson, Y.-S. Lai, C. T. Lowden, M. P. Lynch, J. S. Mendoza, M. M. Murphy, J. W. Wilson, L. M. Ballas, K. Carter, J. W. Darges, J. E. Davis, F. R. Hubbard and M. L. Stamper, “Synthesis and Protein Kinase Inhibitory Activity of Balanol Analogues with Modified Benzophenone Subunits,” Journal of Medicinal Chemistry, Vol. 45, No. 12, 2002, pp. 2624-2643. doi:10.1021/jm020018f
  4. S. Rancon, A. Chaboud, N. Darbour, G. Comte, C. Bayet, P.-N. Simon, J. Raymond, A. Di Pietro, P. Cabalion and D. Barron, “Natural and Synthetic Benzophenones: Interaction with the Cytosolic Binding Domain of P-Glycoprotein,” Phytochemistry, Vol. 57, No. 4, 2001, pp. 553-557. doi:10.1016/S0031-9422(01)00120-0
  5. H. Ito, E. Nishitani, T. Konoshima, M. Takasaki, M. Kozuka and T. Yoshida, “Flavonoid and Benzophenone Glycosides from Coleogyne ramosissima,” Phytochemistry, Vol. 54, No. 7, 2000, pp. 695-700.
  6. J.-C. Li and T. Nohara, “Benzophenone C-Glucosides from Polygala Telephioides,” Chemical & Pharmaceutical Bulletin, Vol. 48, No. 9, 2000, pp. 1354-1355. doi:10.1248/cpb.48.1354
  7. B. M. O’Keefe, N. Simmons and S. F. Martin, “Carbonylative Cross-Coupling of ortho-Disubstituted Aryl Io dides. Convenient Synthesis of Sterically Hindered Aryl Ketones,” Organic Letters, Vol. 10, No. 22, 2008, pp. 5301-5304. doi:10.1021/ol802202j
  8. R. F. Heck, “A Synthesis of Diaryl Ketones from Arylmercuric Salts,” Journal of the American Chemical Society, Vol. 90, No. 20, 1968, pp. 5546-5548. doi:10.1021/ja01022a040
  9. A. Schoenberg, I. Bartoletti and R. F. Heck, “PalladiumCatalyzed Carboalkoxylation of Aryl, Benzyl, and Vinylic Halides,” Journal of Organic Chemistry, Vol. 39, No. 23, 1974, pp. 3318-3326. doi:10.1021/jo00937a003
  10. A. Schoenberg and R. F. Heck, “Palladium-Catalyzed Amidation of Aryl, Heterocyclic, and Vinylic Halides,” Journal of Organic Chemistry, Vol. 39, No. 23, 1974, pp. 3327-3331. doi:10.1021/jo00937a004
  11. J.-J. Brunetand R. Chauvin, “Synthesis of Diarylketones through Carbonylative Coupling,” Chemical Society Reviews, Vol. 24, No. 2, 1995, p. 89. doi:10.1039/cs9952400089
  12. Y. Tamaru and M. Kimura, “Reactions of Acylpalladium Derivatives with Organometals and Related Carbon Nucleophiles,” Handbook of Organopalladium Chemistry for Organic Synthesis, Vol. 2, 2002, pp. 2425-2454.
  13. V. Farina, V. Krishnamurthy and W. J. Scott, “Stille Reaction,” Organic Reactions, Vol. 50, No. 1, 1997, pp. 1- 652.
  14. S.-K. Kang, T. Yamaguchi, T.-H. Kim and P.-S. Ho, “Copper-Catalyzed Cross-Coupling and Carbonylative Cross-Coupling of Organostannanes and Organoboranes with Hypervalent Iodine Compounds,” Journal of Organic Chemistry, Vol. 61, No. 26, 1996, pp. 9082-9083. doi:10.1021/jo962033w
  15. A. M. Echavarren and J. K. Stille, “Palladium-Catalyzed Coupling of Vinyl Epoxides with Organostannanes,” Journal of the American Chemical Society, Vol. 110, No. 12, 1988, pp. 4039-4041. doi:10.1021/ja00220a054
  16. J. K. Stille, “The Palladium-Catalyzed Cross-Coupling Reaction of Organotin Reagents with Organic Electrophiles,” Angewandte Chemie International Edition English, Vol. 25, No. 6, 1986, pp. 508-524. doi:10.1002/anie.198605081
  17. M. Tanaka, “Unsymmetrical Ketone Synthesis from Organic Halides, Carbon Monoxide, and Organotin Compounds Catalyzed by a Palladium Complex,” Tetrahdron Letters, Vol. 20, No. 28, 1979, pp. 2601-2602. doi:10.1016/S0040-4039(01)86360-7
  18. V. Sans, A. M. Trzeciak, S. Luis and J. J. Ziolkowski, “PdCl2(P(OPh)(3))(2) Catalyzed Coupling and Carbonylative Coupling of Phenylacetylenes with Aryl Iodides in Organic Solvents and in Ionic Liquids,” Catalysis Letters, Vol. 109, No. 1-2, 2006, pp. 37-41. doi:10.1007/s10562-006-0053-7
  19. P. J. Tambade, Y. P. Patil, N. S. Nandurkar and B. M. Bhanage, “Copper-Catalyzed, Palladium-Free Carbonylative Sonogashira Coupling Reaction of Aliphatic and Aromatic Alkynes with Iodoaryls,” Synle, No. 6, 2008, pp. 886-888.
  20. N. Haddad, J. Tan and V. Farina, “Convergent Synthesis of the Quinolone Substructure of BILN 2061 via Carbonylative Sonogashira Coupling/Cyclization,” Journal of Organic Chemistry, Vol. 71, No. 13, 2006, pp. 5031-5034. doi:10.1021/jo060556q
  21. M. S. M. Ahmed and A. Mori, “Carbonylative Sonogashira Coupling of Terminal Alkynes with Aqueous Ammonia,” Organic Letters, Vol. 5, No. 17, 2003, pp. 3057- 3060. doi:10.1021/ol035007a
  22. S. Torii, H. Okomoto, L. H. Xu, M. Sadakane, M. V. Shostakovsky, A. B Ponomaryov and V. N. Kalinin, “Syntheses of Chromones and Quinolones via Pd-Catalyzed Carbonylation of O-Iodophenols and Anilines in the Presence of Acetylenes,” Tetrahdron, Vol. 49, No. 31, 1993, pp. 6773-6784. doi:10.1016/S0040-4020(01)80421-X
  23. T. Ohe, K. Ohe, S. Uemura and N. Sugita, “Palladium- (0)-Catalyzed Carbonylation of Alkenyland Arylborates and Boronic Acids with Carbon Monoxide,” Journal of Organometallic Chemistry, Vol. 344, No. 1, 1988, pp. c5- c7. doi:10.1016/0022-328X(88)80220-1
  24. T. Ishiyama, H. Kizaki, T. Hayashi, A. Suzuki and N. Miyaura, “Palladium-Catalyzed Carbonylative CrossCoupling Reaction of Arylboronic Acids with Aryl Electrophiles:  Synthesis of Biaryl Ketones,” Journal of Organic Chemistry, Vol. 63, No. 14, 1998, pp. 4726-4731. doi:10.1021/jo980417b
  25. M. B. Andrus, Y. Ma, Y. Zang and C. Song, “Palladium-Imidazolium-Catalyzed Carbonylative Coupling of Aryl Diazonium Ions and Aryl Boronic Acids,” Tetrahedron Letters, Vol. 43, No. 50, 2002, pp. 9137-9140. doi:10.1016/S0040-4039(02)02186-X
  26. Q. Wang and C. Chen, “Nickel-Catalyzed Carbonylative Negishi Cross-Coupling Reactions,” Tetrahedron Letters, Vol. 49, No. 18, 2008, pp. 2916-2921. doi:10.1016/j.tetlet.2008.03.035
  27. N. A. Bumagin, A. B. Ponomaryov and I. P. Beletskya, “Ketone Synthesis via Palladium-Catalyzed Carbonylation of Organoaluminium Compounds,” Tetrahedron Letters, Vol. 26, No. 39, 1985, pp. 4819-4822. doi:10.1016/S0040-4039(00)94960-8
  28. T. Yamamoto, T. Kohara and A. Yamamoto, “Selective Formation of Ketone, Diketone and Aldehyde by the Co Insertion into Nickel-Alkyl Bonds of Dialkylnickel Complexes. A Novel Nickel-Catalyzed Syntheses of Ketones and Tertiary Alcohols from Grignard Reagents, Aryl Halides, and Carbon Monoxide,” Chemistry Letters, Vol. 5, No. 11, 1976, pp. 1217-1220. doi:10.1246/cl.1976.1217
  29. Y. Hatanaka, S. Fukushima and T. Hiyama, “Carbonylative Coupling Reaction of Organofluorosilanes with Organic Halides Promoted by Fluoride Ion and Palldium Catalyst,” Tetrahedron, Vol. 48, No. 11, 1992, pp. 2113- 2126. doi:10.1016/S0040-4020(01)88878-5
  30. Y. Hatanaka and T. Hiyama, “Highly Selective CrossCoupling Reactions of Organosilicon Compounds Mediated by Fluoride Ion and a Palladium Catalyst,” Synlett, Vol. 1991, No. 12, 1991, pp. 845-853. doi:10.1055/s-1991-20899
  31. Y. Hatanaka and T. Hiyama, “Palladium-Catalyzed Carbonylative Coupling of Arylfluorosilanes with Aryl Iodides. A Convenient Synthesis of Diaryl Ketones,” Chemistry Letters, Vol. 18, No. 11, 1989, pp. 2049-2052. doi:10.1246/cl.1989.2049
  32. E. A. B. Kantchev, C. J. O’Brien and M. G. Organ, “Palladium Complexes of N-Heterocyclic Carbenes as Catalysts for Cross-Coupling Reactions-A Synthetic Chemist’s Perspective,” Angewandte Chemie International Edition, Vol. 46, No. 16, 2007, pp. 2768-2813. doi:10.1002/anie.200601663
  33. K. J. Covell and D. S. McGuinness, “Redox Processes Involving Hydrocarbylmetal (N-Heterocyclic Carbene) Complexes and Associated Imidazolium Salts: Ramifications for Catalysis,” Coordination Chemistry Reviews, Vol. 248, No. 7-8, 2004, pp. 671-681. doi:10.1016/j.ccr.2004.02.006
  34. W. A. Herrmann, “N-Heterocyclic Carbenes: A New Concept in Organometallic Catalysis,” Angewandte Chemie International Edition, Vol. 41, No. 8, 2002, pp. 1290- 1309. doi:10.1002/1521-3773(20020415)41:8<1290::AID-ANIE1290>3.0.CO;2-Y
  35. A. C. Hillier, G. A. Grasa, M. S. Viciu, H. M. Lee, C. Yang and S. P. Nolan, “Catalytic Cross-Coupling Reactions Mediated by Palladium/Nucleophilic Carbene Systems,” Journal of Organometallic Chemistry, Vol. 653, No. 1-2, 2002, pp. 69-82. doi:10.1016/S0022-328X(02)01154-3
  36. P. Andrea, P. Gabor, P. Zoltan and K. Laszlo, “Carbonylative and Direct Suzuki-Miyaura Cross-Coupling Reactions with 1-Iodo-Cyclohexene,” Journal of Molecular Catalysis, Vol. 255, No. 1-2, 2006, pp. 97-102. doi:10.1016/j.molcata.2006.03.070
  37. L. M. Daniela, M. A. Heiddyand and C. S. A. Lucia, “Microwave-Assisted Suzuki Reaction Catalyzed by Pd(0)- PVP Nanoparticles,” Tetrahedron Letters, Vol. 51, No. 52, 2010, pp. 6814-6817. doi:10.1016/j.tetlet.2010.09.145


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