English

• 1. INTRODUCTION

  Since the Suzuki-Miyaura cross-coupling (SMC) reaction was first published by Suzuki and Miyaura in 1979, it has become one of the most powerful tools for forming C–C bonds, especially for the preparation of biaryls^{[1, 2]}. The biaryl unit presents in many natural products and is an important structure in pharmaceuticals, materials, and catalysis^{[3, 4]}. Transition metals, especially palladium, are important catalysts and can make the SMC reactions go smoothly. Over the past decades, researchers have made an in-depth study on palladium catalysts and the results showed that the introduction of ligands significantly improved the catalytic activity of palladium catalysts^[5]. So far, various ligands have been reported, such as phosphine ligands, nitrogen-based ligands, N-heterocyclic carbene (NHC) ligands, etc^[6-17]. Compared with the high cost and toxicity of phosphine ligands and the tedious synthesis of NHC ligands, nitrogen-based ligands showed some advantages like simplicity, non-toxicity and cheapness^[18].

  So far, various types of nitrogen-based ligands have been reported. However, there are still challenges for sterically hindered aryl chlorides and aryl boronic acids. In our pervious study, we have reported a palladium pre-catalyst bearing bulky imidazole ligands^[19]. Bulky imidazole ligands greatly enhanced the stabilization and improved the initiation of palladium pre-catalysts. It exhibited excellent catalytic activity for SMC reactions of aryl chlorides without steric hindrance at room temperature in air. However, no attempt has been made on sterically hindered aryl chlorides and aryl boronic acids. Therefore, it is urgent to develop simple and efficient palladium(Ⅱ) catalysts for sterically hindered aryl chlorides.

  Herein, a series of new palladium(Ⅱ) complexes with bulky 2-methyl-1-(triphenylmethyl)-1H-imidazole, 4-methyl-1-(triphenylmethyl)-1H-imidazole or 1-(triphenylmethyl)-1H-1,2,4-triazole azole ligands are reported for the SMC reaction of sterically hindered aryl chlorides with arylboronic acids in air.

  2. EXPERIMENTAL

  2.1 Reagents and general techniques

  All reagents and solvents were obtained from commercial sources. 2-Methyl-1-(triphenylmethyl)-1H-imidazole^[20], 4-methyl-1-(triphenylmethyl)-1H-imidazole^[21], and 1-(triphenylmethyl)-1H-1,2,4-triazole^[22] were synthesized according to the references. NMR spectra were recorded on a Bruker AV 400. X-ray diffraction of complex 1 was performed using a Bruker APEXⅡ CCD diffractometer. Suitable crystals of complexes 2 and 3 were selected and put on a SuperNova, Dual, Cu at home/near, AtlasS2 diffractometer.

  2.2 General experimental procedure for the syntheses of complexes 1~3

  Azole ligand (1.0 mmol) and PdCl₂ (0.088 g, 0.5 mmol) were placed in a 25 mL Schlenk flask under N₂ atmosphere. Anhydrous THF (6 mL) was added to the reaction system and then, the mixture was heated to 60 ℃ for 12 h. After the reaction was completed, the mixture was cooled to room temperature and filtered. Yellow solid complexes 1~3 were obtained by washing residues with THF.

  Complex 1  Yield: 95% (391 mg, 0.475 mmol). ¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.32 (s, 19H), 7.11 (s, 2H), 7.06 (d, J = 4.0 Hz, 10H), 6.60 (s, 2H), 2.21 (s, 6H). ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 148.4, 141.1, 129.9, 128.2, 128.2, 126.6, 121.6, 18.7. Anal. Calcd. (%) for C₄₆H₄₀Cl₂N₄Pd: C, 66.88; H, 4.88; N, 6.78. Found (%): C, 67.04; H, 4.57; N, 6.69.

  Complex 2  Yield: 95% (391 mg, 0.475 mmol). ¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.58 (s, 2H), 7.33 (s, 19H), 7.08 (d, J = 4.0 Hz, 10H), 6.42 (s, 2H), 2.65 (s, 6H). ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 141.3, 139.2, 137.5, 129.7, 128.3, 128.2, 118.7, 14.4. Anal. Calcd. (%) for C₄₆H₄₀Cl₂N₄Pd: C, 66.88; H, 4.88; N, 6.78. Found (%): C, 67.11; H, 4.69; N, 6.71.

  Complex 3  Yield: 95% (379 mg, 0.475 mmol). ¹H NMR (400 MHz, CDCl₃) δ (ppm): 8.60 (s, 2H), 8.47 (s, 2H), 7.36 (d, J = 4.0 Hz, 18H), 7.07 (d, J = 4.0 Hz, 12H). ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 150.5, 146.6, 140.5, 129.9, 128.8, 128.3, 80.0. Anal. Calcd. (%) for C₄₂H₃₄Cl₂N₆Pd: C, 63.05; H, 4.28; N, 10.50. Found (%): C, 64.12; H, 4.15; N, 10.69.

  2.3 General procedure for Suzuki-Miyaura coupling reaction of sterically hindered aryl chlorides

  A test tube was charged with aryl chloride (0.125 mmol), boronic acid (0.15 mmol), K₃PO₄ (0.25 mmol), H₂O (0.1 mL), isopropanol (0.1 mL) and pre-catalyst (0.1 mol %), and the mixture was heated at 45 ℃ for 40 h. After the reaction completed, the mixture was extracted three times with CH₂Cl₂ (3 × 2 mL), dried over Na₂SO₄ and filtered, and the solvent was removed under vacuum. Further purification of the products was achieved by flash chromatography on a silica gel column.

  2.4 Structure determination

  Single crystals of complexes 1~3 were obtained by slowly evaporating a concentrated solution of dichloromethane and petroleum ether. Yellow single crystals of complexes 1~3 (0.22mm × 0.21mm × 0.18mm, 0.18mm × 0.17mm × 0.16mm, and 0.25mm × 0.22mm × 0.20mm, respectively) are selected for single-crystal X-ray diffraction analysis and the data of complex 1 were collected on a Bruker SMART APEX Ⅱ CCD diffractometer equipped with a graphite-monochromated MoKa radiation (λ = 0.71073 Å) using a φ-ω scan technique in the range of 2.18≤θ≤26.49° at 296(2) K. The structure was solved by direct methods with SHELXS-2014/7^[23]. A full-matrix least-squares refinement on F² was carried out using SHELXL-2014/7^[24]. The crystals of complexes 2 and 3 were kept at 293(2) K during data collection. Using Olex2^[25], the structures were solved with the ShelXT^[23] structure solution program using Intrinsic Phasing and refined with the ShelXL^[24] refinement package using least-squares minimization. All non-hydrogen atoms were refined anisotropically, and the hydrogen atoms were generated geometrically.

  For complex 1~3, a total of 23981, 7665, and 7744 reflections were recorded respectively in the ranges of 2.18≤θ≤26.49º (–15≤h≤15, –20≤k≤17, –23≤l≤20) with 3997 unique ones (R_int = 0.1226), 4.58≤2θ≤50.02º (–11≤h≤11, –12≤k≤12, –13≤l≤13) with 7665 unique ones (R_sigma = 0.0790), and 4.31≤2θ≤50.02º (–20≤h≤18, –15≤k≤14, –19≤l≤19) with 3114 unique ones (R_int = 0.0320, R_sigma = 0.0446), respectively.

  3. RESULTS AND DISCUSSION

  3.1 Crystal structural description of complexes 1~3

  The crystal structures of complexes 1~3 are shown in Fig. 1. Complex 1 is orthorhombic in Pbca space group, 2 is triclinic in P$ \overline 1 $ space group, and 3 is monoclinic in C2/c space group. Selected bond lengths and bond angles for all complexes are listed in Table 1. The metal palladium centre coordinates with two chlorine atoms and two ligands at the same time, forming a four-coordinated square planar geometry. The two ligands are twisted in the molecule due to the steric hindrance. In complexes 1~3, the Pd(1)–N(1) distances are 2.020(3), 2.019(4) and 2.012(2) Å, the Pd(1)–Cl(1) distances are 2.3044(9), 2.3213(14) and 2.3004(7) Å, and the N(1)– Pd(1)–Cl(1) bond angles are 89.56(8), 88.18(13) and 89.91(6)^o, respectively. The spatial structures of the three complexes are similar to those reported in literatures^[26-29].

  Figure 1

  

  Figure 1.  X-ray single-crystal structures of complexes 1~3. All hydrogen atoms are omitted for clarity

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  Table 1

  

  Table 1.  Selected Bond Lengths (Å) and Bond Angles (°)

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  1			2			3
  Bond	Dist.		Bond	Dist.		Bond	Dist.
  Pd(1)–N(1)	2.020(3)		Pd(1)–N(1)	2.019(4)		Pd(1)–N(1)	2.012(2)
  Angle	(°)		Angle	(°)		Angle	(°)
  N(1)–Pd(1)–Cl(1)	89.56(8)		N(1)–Pd(1)–Cl(1)	88.18(13)		N(1)–Pd(1)–Cl(1)	89.91(6)

  No classical hydrogen bonds are found in complexes 1~3 analyzed by the crystal software (PLATON Windows Taskbar). However, for 1, they are linked together by two non-classical intermolecular hydrogen bonds (C–H···Cl bonds) (Fig. 2). The distance between the acceptors and donors for C(4)– H(4A)···Cl(1) hydrogen bond is 3.432(4) Å. Furthermore, a two-dimensional (2D) supramolecular network was built from supramolecular dimmers through intermolecular hydrogen bonds (C–H···Cl), as shown in Fig. 3.

  Figure 2

  

  Figure 2.  Hydrogen bonds (dashed lines) of complex 1

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  Figure 3

  

  Figure 3.  2D packing diagram of complex 1 formed by hydrogen bonds. Non-hydrogen bonding H atoms are omitted for clarity

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  3.2 Catalytic activity

  The catalytic performance of complexes 1~3 was evaluated utilizing o-methyl chlorobenzene and o-methylben-zeneboronic acid as the model substrates at 45 ℃ under air conditions (Table 2). Initially, the SMC reaction was performed in the presence of 1 (0.1 mol%) using K₃PO₄ as a base and a variety of solvents were screened. The results showed that a high yield of 88% was obtained after 40 h in i-PrOH/H₂O (1:1) (entry 5). For other solvents, such as EtOH, i-PrOH, H₂O and EtOH/H₂O (1:1), relatively low yields of 70%, 75%, 78% and 85%, respectively were obtained (entries 1~4). Next, we screened the bases. For K₂CO₃, NaHCO₃, Cs₂CO₃, and KOH, good to excellent yields were afforded (entries 6~9). So, the optimization of reaction conditions revealed that the best solvent was i-PrOH/H₂O (1:1) and the best base was K₃PO₄. The catalytic performance of 2 and 3 was also investigated under the optimum reaction conditions and they all provided 6Aa in a high yield of 90%.

  Table 2

  

  Table 2.  Optimization of the Suzuki Coupling of o-Methyl Chlorobenzene with o-Methylbenzeneboronic Acid^{a, b}

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  entry	base	solvent	yield (%)b
  1	K3PO4	EtOH	70
  2	K3PO4	i-PrOH	75
  3	K3PO4	H2O	78
  4	K3PO4	EtOH/H2O (1:1)	85
  5	K3PO4	i-PrOH/H2O (1:1)	88
  6	K2CO3	i-PrOH/H2O (1:1)	85
  7	NaHCO3	i-PrOH/H2O (1:1)	65
  8	Cs2CO3	i-PrOH/H2O (1:1)	80
  9	KOH	i-PrOH/H2O (1:1)	78
  10c	K3PO4	i-PrOH/H2O (1:1)	90
  11d	K3PO4	i-PrOH/H2O (1:1)	90
  a Reactions conditions: o-methyl chlorobenzene 4A (0.125 mmol), o-methylbenzeneboronic acid 5a (0.15 mmol), 1 (0.1 mol% Pd), base (0.25 mmol), solvent (0.2 mL), 45 ℃. b Isolated yields. c 2 (0.1 mol%). d 3 (0.1 mol%)

  Encouraged by the above results, we then expanded the range of sterically hindered aryl chlorides to synthesize biaryls 6 with different substituents using palladium precatalysts 1, 2 and 3. As shown in Table 3, o-methyl-phenylboronic acid 5a was easily coupled with aryl chlorides containing different substituents, such as 2-methyl and 2,5-dimethyl, and the products (6Aa and 6Ba) were prepared in good to high yields (85~90%). Reactions of 2-methyl chlorobenzene with 2-methyl-4-fluorophenyl and 2,5-dimethylphenyl boronic acid gave the coupling products 6Ab and 6Ac in excellent yields of 95%~98%, respectively. To our surprise, the reaction of bulky 2,6-dimethyl chlorobenzene with 4-fluorophenyl, 4-methylphenyl, 2-methylphenyl, and 2-methoxyphenyl boronic acid also proceeded smoothly and gave the coupling products 6Cd, 6Ce, 6Ca and 6Cf in good to high yields (83%~90%). However, for 2-fluorophenyl boronic acid, the product 6Cg was obtained in moderate yields (60%~65%). From the above results we could see that the yield of complex 3 is slightly higher than that of 1 and 2. This is mainly due to the good coordination ability of 1-(triphenylmethyl)-1H-1,2,4-triazole ligand, which can effectively improve the stability of complex 3 and improve the rate of transmetalation and reductive elimination.

  Table 3

  

  Table 3.  Suzuki Coupling of Sterically Hindered Aryl Chlorides with Aryl boronic Acids^{a, b}

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  a Reactions conditions: sterically hindered aryl chlorides (0.125 mmol), aryl boronic acids (0.15 mmol), catalyst (0.1 mol% Pd), K3PO4 (0.25 mmol), H2O/i-PrOH (0.2 mL, 1:1, v/v), 45 ℃, 40 h. b Isolated yields

  4. CONCLUSION

  In conclusion, three new palladium(Ⅱ) complexes containing two bulky azole ligands have been developed. Bulky azole ligands not only enhanced the stabilization of pre-catalysts, but also improved the catalytic efficiency of Suzuki-Miyaura cross-coupling of sterically hindered aryl chlorides. Various sterically hindered biaryl products were obtained in good to excellent yields with a low catalyst loading (0.1 mol%) in aqueous media. This provides an important theoretical basis for the study of other transition metal complexes.

  
  
• 1. [1]

     Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Aryl-aryl bond formation one century after the discovery of the Ullmann reaction. Chem. Rev. 2002, 102, 1359–1470. doi: 10.1021/cr000664r

  2. [2]

     Tsuji, J. Palladium Reagents and Catalysts. John Wiley and Sons: New York 1995.

  3. [3]

     Brunel, J. M. Update 1 of: BINOL: a versatile chiral reagent. Chem. Rev. 2007, 107, PR1–PR45. doi: 10.1021/cr078004a

  4. [4]

     Pu, L. 1, 1΄-binaphthyl dimers, oligomers, and polymers:   molecular recognition, asymmetric catalysis, and new materials. Chem. Rev. 1998, 98, 2405–2494. doi: 10.1021/cr970463w

  5. [5]

     Christmann, U.; Vilar, R. Monoligated palladium species as catalysts in cross-coupling reactions. Angew. Chem., Int. Ed. 2005, 44, 366–374. doi: 10.1002/anie.200461189

  6. [6]

     Liu, G. Y.; Han, F. W.; Liu, C. X.; Wu, H. L.; Zeng, Y. F.; Zhu, R. J.; Yu, X.; Rao, S.; Huang, G. P.; Wang, J. H. A highly active catalyst system for Suzuki-Miyaura coupling of aryl chlorides. Organometallics. 2019, 38, 1459–1467. doi: 10.1021/acs.organomet.8b00883

  7. [7]

     Ormerod, D.; Dorbec, M.; Merkul, E.; Kaval, N.; Lefèvre, N.; Hostyn, S.; Eykens, L.; Lievens, J.; Sergeyev, S.; Maes, B. U. W. Synthesis of Pd complexes containing tailed NHC ligands and their use in a semicontinuous membrane-assisted Suzuki cross-coupling process. Org. Process Res. Dev. 2018, 22, 1509–1517. doi: 10.1021/acs.oprd.8b00273

  8. [8]

     Liu, G. Y.; Liu, C. X.; Han, F. W.; Wang, Z. L.; Wang, J. H. Highly active palladium catalysts containing a 1,10-phenanthroline analogue N-heterocyclic carbene for room temperature Suzuki-Miyaura coupling reactions of aryl chlorides with arylboronic acids in aqueous media. Tetra. Lett. 2017, 58, 726–731. doi: 10.1016/j.tetlet.2016.12.071

  9. [9]

     Guram, A. S. Enabling palladium/phosphine-catalyzed cross-coupling reactions for practical applications. Org. Process Res. Dev. 2016, 20, 1754–1764. doi: 10.1021/acs.oprd.6b00233

  10. [10]

      Gildner, P. G.; Colacot, T. J. Reactions of the 21st century: two decades of innovative catalyst design for palladium-catalyzed cross-couplings. Organometallics. 2015, 34, 5497–5508. doi: 10.1021/acs.organomet.5b00567

  11. [11]

      Melvin, P. R.; Nova, A.; Balcells, D.; Dai, W.; Hazari, N.; Hruszkewycz, D. P.; Shah, H. P.; Tudge, M. T. Design of a versatile and improved precatalyst scaffold for palladium-catalyzed cross-coupling: (η³-1-^tBu-indenyl)₂(μ-Cl)₂Pd₂. ACS Catal. 2015, 5, 3680–3688. doi: 10.1021/acscatal.5b00878

  12. [12]

      Li, H. B.; Johansson Seechurn, C. C. C.; Colacot, T. J. Development of preformed Pd catalysts for cross-coupling reactions, beyond the 2010 Nobel Prize. ACS Catal. 2012, 2, 1147–1164. doi: 10.1021/cs300082f

  13. [13]

      Valente, C.; Çalimsiz, S.; Hoi, K. H.; Mallik, D.; Sayah, M.; Organ, M. G. The development of bulky palladium NHC complexes for the most-challenging cross-coupling reactions. Angew. Chem., Int. Ed. 2012, 51, 3314–3332. doi: 10.1002/anie.201106131

  14. [14]

      Miura, M. Rational ligand design in constructing efficient catalyst systems for Suzuki-Miyaura coupling. Angew. Chem., Int. Ed. 2004, 43, 2201–2203. doi: 10.1002/anie.200301753

  15. [15]

      Han, F. W.; Xu, Y.; Zhu, R. J.; Liu, G. Y.; Chen, C.; Wang, J. H. Highly active NHC-Pd(Ⅱ) complexes for cross coupling of aryl chlorides and arylboronic acids: an investigation of the effect of remote bulky groups. New J. Chem. 2018, 42, 7422–7427. doi: 10.1039/C8NJ01047A

  16. [16]

      Li, Y.; Han, F. W.; Xu, Z. Y.; Wang, R.; Yan, C. X.; Ou, Y. J.; Lu, Q.; Liu, G. Y.; Zeng, Y. F. Synthesis, crystal structure and catalytic activity of a Pd-PEPPSI complex bearing bromine group. Chin. J. Struct. Chem. 2019, 38, 429–433.

  17. [17]

      Aydın, A. A new palladium complex containing the mixture of carbene and phosphine ligands: synthesis, crystal structure and spectral FT-IR, NMR and UV-Vis researches. Chin. J. Struct. Chem. 2019, 38, 1664–1672.

  18. [18]

      de Meijere, A.; Diederich, F. Metal-catalyzed cross coupling reactions, 2nd edn., Wiley-VCH, Weinheim 2004.

  19. [19]

      Liu, C. X.; Liu, G. Y.; Zhao, H. K. A highly active Pd(Ⅱ) complex with 1-tritylimidazole ligand for Suzuki-Miyaura and Heck coupling reactions. Chin. J. Chem. 2016, 34, 1048–1052. doi: 10.1002/cjoc.201600272

  20. [20]

      Liu, Y.; Ren, W. M.; Liu, C.; Fu, S.; Wang, M.; He, K. K.; Li, R. R.; Zhang, R.; Lu, X. B. Mechanistic understanding of dinuclear cobalt(Ⅲ) complex mediated highly enantioselective copolymerization of meso-epoxides with CO₂. Macromolecules. 2014, 47, 7775–7788. doi: 10.1021/ma5019186

  21. [21]

      Tran, P. T.; Hoang, V. H.; Thorat, S. A.; Kim, S. E.; Ann, J.; Chang, Y. J.; Nam, D. W.; Song, H.; Mook-Jung, I.; Lee, J.; Lee, J. Structure-activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template. Bioorgan. Med. Chem. 2013, 21, 3821–3830. doi: 10.1016/j.bmc.2013.04.005

  22. [22]

      Rezaei, Z.; Khabnadideh, S.; Pakshir, K.; Hossaini, Z.; Amiri, F.; Assadpour, E. Design, synthesis, and antifungal activity of triazole and benzotriazole derivatives. Eur. J. Med. Chem. 2009, 44, 3064–3067. doi: 10.1016/j.ejmech.2008.07.012

  23. [23]

      Sheldrick, G. M. SHELXT-integrated space-group and crystal structure determination. Acta Crystallogr. A 2015, 71, 3–8. doi: 10.1107/S2053273314026370

  24. [24]

      Sheldrick, G. M. Crystal structure refinement with SHELXL. Acta Crystallogr. C 2015, 71, 3–8. doi: 10.1107/S2053229614024218

  25. [25]

      Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. OLEX₂: a complete structure solution, refinement and analysis program. J. Appl. Crystallogr. 2009, 42, 339–341. doi: 10.1107/S0021889808042726

  26. [26]

      Xi, C. J.; Wu, Y. W.; Yan, X. Y. cis-Fashioned palladium(Ⅱ) complexes of 2-phenylbenzimidazole ligands: synthesis, characterization, and catalytic behavior towards Suzuki-Miyaura reaction. J. Organomet. Chem. 2008, 693, 3842–3846. doi: 10.1016/j.jorganchem.2008.09.042

  27. [27]

      Gurbuz, N.; Özdemir, İ.; Çetinkaya, B.; Seçkin, T. Silica-supported 3-4,5-dihydroimidazol-1-yl-propyltriethoxysilanedichloropalladium(Ⅱ) complex: Heck and Suzuki cross-coupling reactions. Appl. Organomet. Chem. 2003, 17, 776–780. doi: 10.1002/aoc.524

  28. [28]

      Trivedi, M.; Singh, G.; Nagarajan, R.; Rath, N. P. Imidazole containing palladium(Ⅱ) complexes as efficient pre-catalyst systems for Heck and Suzuki coupling reaction: synthesis, structural characterization and catalytic properties. Inorg. Chim. Acta. 2013, 394, 107–116. doi: 10.1016/j.ica.2012.08.003

  29. [29]

      Szulmanowicz, M. S.; Zawartka, W.; Gniewek, A.; Trzeciak, A. M. Structure, dynamics and catalytic activity of palladium(Ⅱ) complexes with imidazole ligands. Inorg. Chim. Acta. 2010, 363, 4346–4354. doi: 10.1016/j.ica.2010.08.037

• 

  Figure 1  X-ray single-crystal structures of complexes 1~3. All hydrogen atoms are omitted for clarity

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  Figure 2  Hydrogen bonds (dashed lines) of complex 1

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  Figure 3  2D packing diagram of complex 1 formed by hydrogen bonds. Non-hydrogen bonding H atoms are omitted for clarity

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  Table 1.  Selected Bond Lengths (Å) and Bond Angles (°)

  1			2			3
  Bond	Dist.		Bond	Dist.		Bond	Dist.
  Pd(1)–N(1)	2.020(3)		Pd(1)–N(1)	2.019(4)		Pd(1)–N(1)	2.012(2)
  Angle	(°)		Angle	(°)		Angle	(°)
  N(1)–Pd(1)–Cl(1)	89.56(8)		N(1)–Pd(1)–Cl(1)	88.18(13)		N(1)–Pd(1)–Cl(1)	89.91(6)

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  Table 2.  Optimization of the Suzuki Coupling of o-Methyl Chlorobenzene with o-Methylbenzeneboronic Acid^{a, b}

  entry	base	solvent	yield (%)b
  1	K3PO4	EtOH	70
  2	K3PO4	i-PrOH	75
  3	K3PO4	H2O	78
  4	K3PO4	EtOH/H2O (1:1)	85
  5	K3PO4	i-PrOH/H2O (1:1)	88
  6	K2CO3	i-PrOH/H2O (1:1)	85
  7	NaHCO3	i-PrOH/H2O (1:1)	65
  8	Cs2CO3	i-PrOH/H2O (1:1)	80
  9	KOH	i-PrOH/H2O (1:1)	78
  10c	K3PO4	i-PrOH/H2O (1:1)	90
  11d	K3PO4	i-PrOH/H2O (1:1)	90
  a Reactions conditions: o-methyl chlorobenzene 4A (0.125 mmol), o-methylbenzeneboronic acid 5a (0.15 mmol), 1 (0.1 mol% Pd), base (0.25 mmol), solvent (0.2 mL), 45 ℃. b Isolated yields. c 2 (0.1 mol%). d 3 (0.1 mol%)

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  Table 3.  Suzuki Coupling of Sterically Hindered Aryl Chlorides with Aryl boronic Acids^{a, b}

  a Reactions conditions: sterically hindered aryl chlorides (0.125 mmol), aryl boronic acids (0.15 mmol), catalyst (0.1 mol% Pd), K3PO4 (0.25 mmol), H2O/i-PrOH (0.2 mL, 1:1, v/v), 45 ℃, 40 h. b Isolated yields

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•