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Cite this: DOI: 10.1039/c4cc00474d Received 20th January 2014, Accepted 21st February 2014
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Synthesis of unsymmetrical imidazolium salts by direct quaternization of N-substituted imidazoles using arylboronic acids† Shiqing Li, Fan Yang, Taiyong Lv, Jingbo Lan, Ge Gao* and Jingsong You*
DOI: 10.1039/c4cc00474d www.rsc.org/chemcomm
Imidazolium salts were conveniently prepared by direct aryl quaternization using arylboronic acids. This process features the tolerance of a broad range of functional groups and excellent chemoselectivity, and is especially effective for the synthesis of unsymmetrical imidazolium salts.
Imidazolium salts are important precursors of N-heterocyclic carbenes1 (NHCs) and useful motifs of functional materials such as anion receptors,2 fluorophores3 and ionic liquids.4 These organic salts are generally synthesized via Arduengo’s classic multicomponent cyclization5 and many variations.6 However, these methods are not practically applicable for the synthesis of unsymmetrical salts, which are very desirable1b and promising ligands/catalysts for asymmetric catalyses.7 Recently, an upgrade ´ and Mauduit et al. allowed the assembly of this method by Basle of unsymmetrical imidazolium salts, but only arylcycloalkylimidazolium salts were synthesized.8
The direct quaternization of N-substituted imidazoles is apparently a straightforward strategy. However, only primary alkyl halides and aryl halides with strong electron withdrawing Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, PR China. E-mail: [email protected], [email protected]; Fax: +86 28-85412203 † Electronic supplementary information (ESI) available. See DOI: 10.1039/c4cc00474d
This journal is © The Royal Society of Chemistry 2014
groups are suitable substrates.9 In 2002, Yoshida and Kunai et al. reported the use of arynes as the aryl source, but N-arylimidazoles could not be arylated to afford 1,3-diarylimidazolium salts.10 Because of our continuous interest in imidazolium compounds,11 we are keen to find a general, convenient and effective method to access imidazolium salts by direct quaternization. We previously reported the use of diaryliodomium salts to quaternize N-substituted imidazoles through copper(III) catalysis.12 Herein, we present a more convenient method by using arylboronic acids. The key to the success of the direct quaternization of imidazoles using diaryliodonium salts relied on the ‘‘hyperleaving group ability’’ of diaryliodonium salts and the super electrophilicity of copper(III), which was oxidized by diaryliodonium salts.12 However, diaryliodonium salts are not easily prepared and aryl-economical (an aryliodide is formed as waste after each arylation). Arylboronic acids, which are one of the most abundant commercially available aryl sources, are known to arylate N–H of imidazoles.13 However, the quaternization of N-substituted imidazoles has not been disclosed yet. A previous study also demonstrated that the highly reactive copper(III) species could be generated in situ from copper(II) by an exotic oxidant in the reaction flask.14 We therefore envisaged that arylboronic acids could be used to directly quaternize N-substituted imidazoles with the help of a copper salt in combination with a suitable oxidant. We initialized the study with the quaternization of N-phenylimidazole 1a by phenylboronic acid 2a in DMF at 100 1C using 10 mol% Cu(OAc)2H2O as the catalyst. The reaction was run in an open flask equipped with a condenser in expectation of the formation of reactive copper(III) species by the air oxidation. NaBF4 (2.5 equiv.) was chosen as the counterion source, considering the weak coordination ability of the tetrafluoroboron anion. To our delight, the desired 1,3-diphenylimidazolium salt 3aa was obtained in 15% yield after chromatography on silica gel (Table 1, entry 1). The GC–MS analysis showed a considerable amount of the phenol byproduct in the crude mixture, which was formed by the oxidation of phenylboronic acid.15 This bypass could be suppressed by using HBF4 instead of
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Table 1
ChemComm
Optimization of the reaction conditionsa
Table 2
Entry
Additive (equiv.)
Oxidant
Yieldb (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
NaBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4/NaBF4 (1.0/1.0) HBF4/NaBF4 (1.0/1.5) HBF4/NaBF4 (2.5/1.0) HBF4/NaBF4 (1.0/2.5) HBF4/NaBF4 (1.0/2.5) HBF4/NaBF4 (1.0/2.5) HBF4/NH4BF4 (1.0/2.5)
Air Air MnO2c K2S2O8c Fe(NO3)39H2O FeCl3 FeCl3 (no air) FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3
15 45 39 61 65 83 0 65d 62 78 85 90 78 e 75 f 92
Scope of the N-substituted imidazolesa,b
a General conditions: 1a (0.25 mmol), 2a (0.375 mmol), Cu(OAc)2H2O (10 mol%), FeCl3 (10 mol%), HBF4 (1.0 equiv.) and NH4BF4 (2.5 equiv.) were stirred in DMF (1 mL) at 100 1C for 10 h under air. b Isolated yields. c 1.0 equivalent. d At 80 1C. e Cu(OAc)2H2O (5 mol%). f FeCl3 (5 mol%).
NaBF4 and the yield was improved to 45% (Table 1, entry 2). After screening a range of oxidants, K2S2O8 and iron(III) showed better activities, and FeCl3 gave the highest yield of 83% (Table 1, entries 3–6). Air was still necessary and the reaction under the nitrogen atmosphere gave only a trace amount of the product (Table 1, entry 7). The reaction run at a lowered temperature of 80 1C resulted in a significantly decreased yield of 65% (Table 1, entry 8). Further exploration showed that this procedure had very poor substrate generality, which was probably due to the strong acidic conditions. We then varied the buffer solution with different ratios of HBF4 and NaBF4. The yield was promoted to 90% at the HBF4/NaBF4 ratio of 1/2.5 (Table 1, entries 9–12). Attempts to cut the usage of either Cu(OAc)2H2O or FeCl3 led to a large diminution of the yields (Table 1, entries 13 and 14). Finally, we obtained the optimal conditions by using NH4BF416 instead of NaBF4 to afford the diphenylimidazolium BF4 salt 3aa in 92% yield (Table 1, entry 15). With the optimized conditions in hand, a variety of N-substituted imidazoles 1 were tested by using phenylboronic acid 2a, and the results are summarized in Table 2. N-Aryl imidazoles with common substituents such as methyl, methoxy, halide, alkynyl, ester and dimethylamino groups at the ortho, meta and para positions of the phenyl ring were all successfully quaternized to afford the corresponding unsymmetrical imidazolium salts in moderate to high yields (Table 2, 3aa–3la). This reaction was not very sensitive to both the steric and electronic factors on the imidazole substrate side. Bulky mesityl and 2,6-diisopropylphenyl substituted imidazoles were smoothly quaternized by 2.0 equiv. of 2a to afford 3ja and 3ka in 66% and 49% yields, respectively. Heteroaryl substitution was also tolerated in this reaction. N-(2-Pyridyl)-imidazole could be selectively quaternized on the nitrogen of imidazole instead of pyridine to form imidazolium salt 3la in 75% yield.
Chem. Commun.
a Reaction conditions: 1 (0.25 mmol), 2a (0.375 mmol), Cu(OAc)2H2O (10 mol%), FeCl3 (10 mol%), HBF4 (1.0 equiv.) and NH4BF4 (2.5 equiv.) were stirred in DMF (1 mL) at 100 1C for 10 h. b Isolated yields. c 2.0 equiv. of phenylboronic acid was used.
N-tert-Butylphenylimidazolium salt 3ma, which could not be obtained by the quaternization of N-phenylimidazole by tert-butyl halides,10,17 was synthesized by the quaternization of N-tert-butylimidazole using 2a in a high yield of 91%. Diphenylimidazolium salt 3na was obtained in 46% yield probably due to the steric hindrance at the 4 and 5 positions. Starting from (R)-1-(1-phenylethyl)-1H-imidazole, chiral imidazolium salt 3oa was assembled in a high yield of 90%, demonstrating a promising access to chiral NHC precursors. To further examine the substrate scope of this method, other boronic acids were tested and the results are summarized in Table 3. The steric effect on the boronic acid side showed a significant impact on this reaction. While o-methylphenylboronic acid only quaternized 1a to give 3ab in 31% yield, m- and p-methoxyphenylboronic acids delivered 3ac and 3ad in 65% and 70% yields, respectively. Biphenylboronic acid directly quaternized 1a to form the corresponding 3ae in 65% yield. Arylboronic acids with electron-withdrawing groups were also suitable arylating reagents. (3-Nitrophenyl)boronic acid quaternized 1a to afford 3af in 72% yield, and (4-acetylphenyl)boronic acid quaternized 1a to give 3ag in a relatively low yield of 57%. Monohalide-substituted diphenylimidazolium salts were successfully obtained in good yields, as exemplified here by the products with fluoride 3ah and bromide 3ai in 73% and 80% yields, respectively. Difunctional imidazolium salts could also be synthesized, but the yields were lowered: symmetrical 1,3-bis(4-bromophenyl)imidazolium salt 3fi was obtained in 43% yield and unsymmetrical imidazolium salt 3fj equipped with bromo and ester groups was gained in 44% yield. These substituents provided opportunities for the further derivation
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Table 3
Scope of the arylboronic acidsa,b
a Reaction conditions: 1 (0.25 mmol), 2 (0.375 mmol), Cu(OAc)2H2O (10 mol%), FeCl3 (10 mol%), HBF4 (1.0 equiv.) and NH4BF4 (2.5 equiv.) were stirred in DMF (1 mL) at 100 1C for 10 h. b Isolated yields.
of novel NHC precursors. It needs to be pointed out that all the imidazolium salts associated with the BF4 anion could be easily metathesized to the corresponding Cl salts by using anion exchange resins.18 For instance, 3aa (in the BF4 form) was converted into 3aa 0 (in the Cl form) in 94% yield (ESI†). Based on our previous study, a possible mechanism was proposed (Scheme 1).12,14 Firstly, the transmetalation of an arylboronic acid with copper acetate formed aryl copper species, which further coordinated with a N-substituted imidazole to form copper(II) intermediate I. In the presence of the counter anion tetrafluoroboron, I was consequently oxidized by iron(III) to form the highly reactive copper(III) intermediate II. The subsequent fast reductive elimination released the product imidazolium salt and generated copper(I) species. The oxygen in air oxidized copper(I) and iron(II) to regenerate copper(II) and iron(III) for the next catalytic cycle. The proton was involved in these two oxidative processes, interpreting the beneficial effect of the acidic environment as well as the inhibition of the oxidation of boronic acids. In addition, the relative congestion
Scheme 1 Proposed mechanism for the quaternization of N-substituted imidazoles with arylboronic acids.
This journal is © The Royal Society of Chemistry 2014
Communication
around the copper center might impede the oxidation of copper(II) to copper(III), resulting in the inferior activity of this reaction toward sterically hindered boronic acids. In summary, we have successfully developed a novel approach for the direct quaternization of N-substituted imidazoles using commercially available arylboronic acids. This method tolerated a broad range of functional groups such as methoxy, halide, ester, acetyl, nitro and N,N-dimethylamino groups, etc. on both the imidazole side and the boronic acid side. The reaction could be run under an air atmosphere, which makes it very convenient and practical. The easy access to functional and unsymmetrical imidazolium salts is especially attractive for novel ligand and material synthesis. We thank the NSFC (Nos 21172159, 21025205 and 21321061) and the NCET-13-0384 for the financial support.
Notes and references 1 (a) W. A. Herrmann, Angew. Chem., Int. Ed., 2002, 41, 1290; ´lez, (b) S. Bellemin-Laponnaz, E. Despagnet-Ayoub, S. Dı´ez-Gonza L. H. Gade, F. Glorius, J. Louie, S. P. Nolan, E. Peris, T. Ritter, M. M. Rogers, S. S. Stahl and T. N. Tekavec, in N-Heterocyclic Carbenes in Transition Metal Catalysis, Topics in Organometallic Chemistry, ed. F. Glorius, Springer, Berlin, Germany, 2007, vol. 21. 2 For reviews, see: (a) J. Yoon, S. K. Kim, N. J. Singh and K. S. Kim, Chem. Soc. Rev., 2006, 35, 355; (b) Z. Xu, S. K. Kim and J. Yoon, Chem. Soc. Rev., 2010, 39, 1457. 3 A. J. Boydston, P. D. Vu, O. L. Dykhno, V. Chang, A. R. Wyatt II, A. S. Stockett, E. T. Ritschdorff, J. B. Shear and C. W. Bielawski, J. Am. Chem. Soc., 2008, 130, 3143. 4 For reviews, see: (a) T. Welton, Chem. Rev., 1999, 99, 2071; (b) R. Giernoth, Angew. Chem., Int. Ed., 2010, 49, 5608. 5 (a) A. J. Arduengo III, US Pat., 5,077,414, 1991; (b) A. J. Arduengo III, R. L. Harlow and M. Kline, J. Am. Chem. Soc., 1991, 113, 361. 6 For a review, see: L. Benhamou, E. Chardon, G. Lavigne, S. Bellemin´sar, Chem. Rev., 2011, 111, 2705. Laponnaz and V. Ce 7 For recent reviews, see: (a) J. Tornatzky, A. Kannenberg and S. Blechert, Dalton Trans., 2012, 41, 8215; (b) F. Wang, L. Liu, W. Wang, S. Li and M. Shi, Coord. Chem. Rev., 2012, 256, 804. 8 P. Queval, C. Jahier, M. Rouen, I. Artur, J.-C. Legeay, L. Falivene, ´visy, L. Cavallo, O. Basle ´ and M. Mauduit, Angew. L. Toupet, C. Cre Chem., Int. Ed., 2013, 52, 14103. 9 Z.-Q. Zhu, S. Xiang, Q.-Y. Chen, C. Chen, Z. Zeng, Y.-P. Cui and J.-C. Xiao, Chem. Commun., 2008, 5016. 10 H. Yoshida, S. Sugiura and A. Kunai, Org. Lett., 2002, 4, 2767. 11 (a) C. Gao, H. Zhou, S. Wei, Y. Zhao, J. You and G. Gao, Chem. Commun., 2013, 49, 1127; (b) H. Zhou, Z. Wang, C. Gao, J. You and G. Gao, Chem. Commun., 2013, 49, 1832; (c) H. Zhou, Y. Zhao, G. Gao, S. Li, J. Lan and J. You, J. Am. Chem. Soc., 2013, 135, 14908; (d) Z. Wang, H. Zhou, J. Hu, J. You and G. Gao, Acta Chim. Sin., 2013, 71, 1257. 12 (a) T. Lv, Z. Wang, J. You, J. Lan and G. Gao, J. Org. Chem., 2013, 78, 5723; (b) T. Lv, L. Yang, Y. Zhao, F. Song, J. Lan, J. You and G. Gao, Chin. Chem. Lett., 2013, 24, 773. 13 (a) P. Y. S. Lam, C. G. Clark, S. Saubern, J. Adams, M. P. Winters, D. M. T. Chan and A. Combs, Tetrahedron Lett., 1998, 39, 2941; (b) J.-B. Lan, L. Chen, X.-Q. Yu, J.-S. You and R.-G. Xie, Chem. Commun., 2004, 188. 14 H. Wang, Y. Wang, C. Peng, J. Zhang and Q. Zhu, J. Am. Chem. Soc., 2010, 132, 13217. 15 (a) J. Xu, X. Wang, C. Shao, D. Su, G. Chen and Y. Hu, Org. Lett., 2010, 12, 1964; (b) H. Yang, Y. Li, M. Jiang, J. Wang and H. Fu, Chem.–Eur. J., 2011, 17, 5652. 16 Using NH4BF4 gave constantly better yields than using NaBF4 when varying different boronic acids. ´sar and C. W. Lehmann, Chem. ¨rstner, M. Alcarazo, V. Ce 17 A. Fu Commun., 2006, 2176. 18 E. M. Higgins, J. A. Sherwood, A. G. Lindsay, J. Armstrong, R. S. Massey, R. W. Alder and A. C. O’Donoghue, Chem. Commun., 2011, 47, 1559.
Chem. Commun.
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Cite this: DOI: 10.1039/c4cc00474d Received 20th January 2014, Accepted 21st February 2014
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Synthesis of unsymmetrical imidazolium salts by direct quaternization of N-substituted imidazoles using arylboronic acids† Shiqing Li, Fan Yang, Taiyong Lv, Jingbo Lan, Ge Gao* and Jingsong You*
DOI: 10.1039/c4cc00474d www.rsc.org/chemcomm
Imidazolium salts were conveniently prepared by direct aryl quaternization using arylboronic acids. This process features the tolerance of a broad range of functional groups and excellent chemoselectivity, and is especially effective for the synthesis of unsymmetrical imidazolium salts.
Imidazolium salts are important precursors of N-heterocyclic carbenes1 (NHCs) and useful motifs of functional materials such as anion receptors,2 fluorophores3 and ionic liquids.4 These organic salts are generally synthesized via Arduengo’s classic multicomponent cyclization5 and many variations.6 However, these methods are not practically applicable for the synthesis of unsymmetrical salts, which are very desirable1b and promising ligands/catalysts for asymmetric catalyses.7 Recently, an upgrade ´ and Mauduit et al. allowed the assembly of this method by Basle of unsymmetrical imidazolium salts, but only arylcycloalkylimidazolium salts were synthesized.8
The direct quaternization of N-substituted imidazoles is apparently a straightforward strategy. However, only primary alkyl halides and aryl halides with strong electron withdrawing Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu 610064, PR China. E-mail: [email protected], [email protected]; Fax: +86 28-85412203 † Electronic supplementary information (ESI) available. See DOI: 10.1039/c4cc00474d
This journal is © The Royal Society of Chemistry 2014
groups are suitable substrates.9 In 2002, Yoshida and Kunai et al. reported the use of arynes as the aryl source, but N-arylimidazoles could not be arylated to afford 1,3-diarylimidazolium salts.10 Because of our continuous interest in imidazolium compounds,11 we are keen to find a general, convenient and effective method to access imidazolium salts by direct quaternization. We previously reported the use of diaryliodomium salts to quaternize N-substituted imidazoles through copper(III) catalysis.12 Herein, we present a more convenient method by using arylboronic acids. The key to the success of the direct quaternization of imidazoles using diaryliodonium salts relied on the ‘‘hyperleaving group ability’’ of diaryliodonium salts and the super electrophilicity of copper(III), which was oxidized by diaryliodonium salts.12 However, diaryliodonium salts are not easily prepared and aryl-economical (an aryliodide is formed as waste after each arylation). Arylboronic acids, which are one of the most abundant commercially available aryl sources, are known to arylate N–H of imidazoles.13 However, the quaternization of N-substituted imidazoles has not been disclosed yet. A previous study also demonstrated that the highly reactive copper(III) species could be generated in situ from copper(II) by an exotic oxidant in the reaction flask.14 We therefore envisaged that arylboronic acids could be used to directly quaternize N-substituted imidazoles with the help of a copper salt in combination with a suitable oxidant. We initialized the study with the quaternization of N-phenylimidazole 1a by phenylboronic acid 2a in DMF at 100 1C using 10 mol% Cu(OAc)2H2O as the catalyst. The reaction was run in an open flask equipped with a condenser in expectation of the formation of reactive copper(III) species by the air oxidation. NaBF4 (2.5 equiv.) was chosen as the counterion source, considering the weak coordination ability of the tetrafluoroboron anion. To our delight, the desired 1,3-diphenylimidazolium salt 3aa was obtained in 15% yield after chromatography on silica gel (Table 1, entry 1). The GC–MS analysis showed a considerable amount of the phenol byproduct in the crude mixture, which was formed by the oxidation of phenylboronic acid.15 This bypass could be suppressed by using HBF4 instead of
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Table 1
ChemComm
Optimization of the reaction conditionsa
Table 2
Entry
Additive (equiv.)
Oxidant
Yieldb (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
NaBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4 (2.5) HBF4/NaBF4 (1.0/1.0) HBF4/NaBF4 (1.0/1.5) HBF4/NaBF4 (2.5/1.0) HBF4/NaBF4 (1.0/2.5) HBF4/NaBF4 (1.0/2.5) HBF4/NaBF4 (1.0/2.5) HBF4/NH4BF4 (1.0/2.5)
Air Air MnO2c K2S2O8c Fe(NO3)39H2O FeCl3 FeCl3 (no air) FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3
15 45 39 61 65 83 0 65d 62 78 85 90 78 e 75 f 92
Scope of the N-substituted imidazolesa,b
a General conditions: 1a (0.25 mmol), 2a (0.375 mmol), Cu(OAc)2H2O (10 mol%), FeCl3 (10 mol%), HBF4 (1.0 equiv.) and NH4BF4 (2.5 equiv.) were stirred in DMF (1 mL) at 100 1C for 10 h under air. b Isolated yields. c 1.0 equivalent. d At 80 1C. e Cu(OAc)2H2O (5 mol%). f FeCl3 (5 mol%).
NaBF4 and the yield was improved to 45% (Table 1, entry 2). After screening a range of oxidants, K2S2O8 and iron(III) showed better activities, and FeCl3 gave the highest yield of 83% (Table 1, entries 3–6). Air was still necessary and the reaction under the nitrogen atmosphere gave only a trace amount of the product (Table 1, entry 7). The reaction run at a lowered temperature of 80 1C resulted in a significantly decreased yield of 65% (Table 1, entry 8). Further exploration showed that this procedure had very poor substrate generality, which was probably due to the strong acidic conditions. We then varied the buffer solution with different ratios of HBF4 and NaBF4. The yield was promoted to 90% at the HBF4/NaBF4 ratio of 1/2.5 (Table 1, entries 9–12). Attempts to cut the usage of either Cu(OAc)2H2O or FeCl3 led to a large diminution of the yields (Table 1, entries 13 and 14). Finally, we obtained the optimal conditions by using NH4BF416 instead of NaBF4 to afford the diphenylimidazolium BF4 salt 3aa in 92% yield (Table 1, entry 15). With the optimized conditions in hand, a variety of N-substituted imidazoles 1 were tested by using phenylboronic acid 2a, and the results are summarized in Table 2. N-Aryl imidazoles with common substituents such as methyl, methoxy, halide, alkynyl, ester and dimethylamino groups at the ortho, meta and para positions of the phenyl ring were all successfully quaternized to afford the corresponding unsymmetrical imidazolium salts in moderate to high yields (Table 2, 3aa–3la). This reaction was not very sensitive to both the steric and electronic factors on the imidazole substrate side. Bulky mesityl and 2,6-diisopropylphenyl substituted imidazoles were smoothly quaternized by 2.0 equiv. of 2a to afford 3ja and 3ka in 66% and 49% yields, respectively. Heteroaryl substitution was also tolerated in this reaction. N-(2-Pyridyl)-imidazole could be selectively quaternized on the nitrogen of imidazole instead of pyridine to form imidazolium salt 3la in 75% yield.
Chem. Commun.
a Reaction conditions: 1 (0.25 mmol), 2a (0.375 mmol), Cu(OAc)2H2O (10 mol%), FeCl3 (10 mol%), HBF4 (1.0 equiv.) and NH4BF4 (2.5 equiv.) were stirred in DMF (1 mL) at 100 1C for 10 h. b Isolated yields. c 2.0 equiv. of phenylboronic acid was used.
N-tert-Butylphenylimidazolium salt 3ma, which could not be obtained by the quaternization of N-phenylimidazole by tert-butyl halides,10,17 was synthesized by the quaternization of N-tert-butylimidazole using 2a in a high yield of 91%. Diphenylimidazolium salt 3na was obtained in 46% yield probably due to the steric hindrance at the 4 and 5 positions. Starting from (R)-1-(1-phenylethyl)-1H-imidazole, chiral imidazolium salt 3oa was assembled in a high yield of 90%, demonstrating a promising access to chiral NHC precursors. To further examine the substrate scope of this method, other boronic acids were tested and the results are summarized in Table 3. The steric effect on the boronic acid side showed a significant impact on this reaction. While o-methylphenylboronic acid only quaternized 1a to give 3ab in 31% yield, m- and p-methoxyphenylboronic acids delivered 3ac and 3ad in 65% and 70% yields, respectively. Biphenylboronic acid directly quaternized 1a to form the corresponding 3ae in 65% yield. Arylboronic acids with electron-withdrawing groups were also suitable arylating reagents. (3-Nitrophenyl)boronic acid quaternized 1a to afford 3af in 72% yield, and (4-acetylphenyl)boronic acid quaternized 1a to give 3ag in a relatively low yield of 57%. Monohalide-substituted diphenylimidazolium salts were successfully obtained in good yields, as exemplified here by the products with fluoride 3ah and bromide 3ai in 73% and 80% yields, respectively. Difunctional imidazolium salts could also be synthesized, but the yields were lowered: symmetrical 1,3-bis(4-bromophenyl)imidazolium salt 3fi was obtained in 43% yield and unsymmetrical imidazolium salt 3fj equipped with bromo and ester groups was gained in 44% yield. These substituents provided opportunities for the further derivation
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Table 3
Scope of the arylboronic acidsa,b
a Reaction conditions: 1 (0.25 mmol), 2 (0.375 mmol), Cu(OAc)2H2O (10 mol%), FeCl3 (10 mol%), HBF4 (1.0 equiv.) and NH4BF4 (2.5 equiv.) were stirred in DMF (1 mL) at 100 1C for 10 h. b Isolated yields.
of novel NHC precursors. It needs to be pointed out that all the imidazolium salts associated with the BF4 anion could be easily metathesized to the corresponding Cl salts by using anion exchange resins.18 For instance, 3aa (in the BF4 form) was converted into 3aa 0 (in the Cl form) in 94% yield (ESI†). Based on our previous study, a possible mechanism was proposed (Scheme 1).12,14 Firstly, the transmetalation of an arylboronic acid with copper acetate formed aryl copper species, which further coordinated with a N-substituted imidazole to form copper(II) intermediate I. In the presence of the counter anion tetrafluoroboron, I was consequently oxidized by iron(III) to form the highly reactive copper(III) intermediate II. The subsequent fast reductive elimination released the product imidazolium salt and generated copper(I) species. The oxygen in air oxidized copper(I) and iron(II) to regenerate copper(II) and iron(III) for the next catalytic cycle. The proton was involved in these two oxidative processes, interpreting the beneficial effect of the acidic environment as well as the inhibition of the oxidation of boronic acids. In addition, the relative congestion
Scheme 1 Proposed mechanism for the quaternization of N-substituted imidazoles with arylboronic acids.
This journal is © The Royal Society of Chemistry 2014
Communication
around the copper center might impede the oxidation of copper(II) to copper(III), resulting in the inferior activity of this reaction toward sterically hindered boronic acids. In summary, we have successfully developed a novel approach for the direct quaternization of N-substituted imidazoles using commercially available arylboronic acids. This method tolerated a broad range of functional groups such as methoxy, halide, ester, acetyl, nitro and N,N-dimethylamino groups, etc. on both the imidazole side and the boronic acid side. The reaction could be run under an air atmosphere, which makes it very convenient and practical. The easy access to functional and unsymmetrical imidazolium salts is especially attractive for novel ligand and material synthesis. We thank the NSFC (Nos 21172159, 21025205 and 21321061) and the NCET-13-0384 for the financial support.
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