Synthesis of Xylyl-Linked Bis-Benzimidazolium Salts and Their Application in the Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling Reaction of Aryl Chlorides

A new series of xylyl-linked bis-benzimidazolium salts were efficiently prepared using a simple preparation method from bis-benzimidazolium precursors featuring highly tunable linkers and wingtips. A highly efficient Suzuki–Miyaura cross-coupling reaction of aryl chlorides within the range of 0.5–2.0 mol% Pd-catalyst loading was observed. Also, di-ortho-substituted biaryl synthesis was achieved.


Introduction
The palladium-catalyzed Suzuki-Miyaura cross-coupling reaction (SMC), which involves the combination of an aryl halide with an arylboronic acid in the presence of a Pd catalyst, is one of the most practical protocols by which to achieve C-C bond formation [1][2][3][4][5]. Aryl chlorides, which are less expensive and more diverse than aryl bromides and iodides, are challenging compounds to use in SMC reactions due to their low C-Cl bond reactivity [6]. Numerous successful examples using a combination of phosphine ligands with Pd have been reported, however, the disadvantages of using such ligands are their difficult preparation, air-sensitivity, expense, and toxicity [7][8][9]. The development of Pd catalysts with phosphine-free ligands has thus received a great amount of attention.
Over the past three decades, the replacement of phosphine ligands with N-heterocyclic carbenes (NHCs) has been shown to be a good choice. Compared with bulky tertiary phosphines, these new NHC ligands exhibit strong σ-donor but poor π-acceptor properties [10]. Metal-NHC complexes exhibit extraordinary heat, air, and moisture stability due to the high dissociation energies of their metal-carbon bonds [11]. Bis-NHC binds to metals to form more stable complexes compared to monodentate NHC complexes, which has led to the development of such ligands attracting great attention in the literature. In addition, the diversity of bis-NHC compounds is also an advantage, as they have tunable linkers and wingtips. In 1998, a chelating bis-NHC ligand was synthesized by Herrmann and co-workers [12] and applied in the Pd-catalyzed SMC reaction of 4-chloroacetophenone and phenylboronic acid at 120 • C for 48 h, resulting in the desired product being formed with a yield of 60%. Numerous successful examples of SMC reactions between aryl chlorides and arylboronic acids employing Pd-bis-NHC complexes or in-situ-formed Pd(OAc) 2 /bis-NHC catalyst systems have been previously reported [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. However, high catalyst loading and the variety of the substrates still present challenge.
The catalytic reaction rate is affected by the nature of the NHC ligand. To obtain efficient bis-NHC ligands, a series of new xylyl-linked bis-benzimidazolium salts was prepared by modifying the wingtips and linkers of a bis-NHC precursor. These salts have the following advantages: (1) our linker contains aryl group which can provide electronic effect, (2) our linker has an additional methylene group compared to currently available NHCs in which the aryl group is directly connected to the bis-benzimidazole moiety that offers more conformational flexibility, and (3) the wingtip delivers electronic and steric effects. Those advantages facilitate the oxidative addition and reductive elimination steps of the SMC reaction. We report herein their application in an in-situ-generated Pd(OAc)2/bis-NHC catalyst system for the SMC reaction of aryl chlorides with arylboronic acids (Figure 1).

Synthesis and Characterization of the Bis-Benzimidazolium Salts 3
According to Scheme 1, the bis-benzimidazolium salts 3 were prepared by the combination of two equivalents of the corresponding N-arylbenzimidazole 2 and one equivalent of the desired dibromides 1 in acetonitrile under reflux to produce the respective products with yields in the range of 50 to 89%. The newly prepared salts were found to be air-and moisture-stable both in the solid state and in solution, and were characterized by 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy.
In the 1 H NMR spectra of 3a-3d, the methylene protons could be observed as a singlet, while the 1 H NMR spectra of 3e and 3f showed an AB spin system for the methylene protons. The benzimidazolium proton signals in the spectra of 3a-3f could be observed in a wide range of between δ 10.15 and 11.57 ppm. The 13 C NMR spectra of 3a-3f showed the NCHN resonances between δ 142.4 and 161.0 ppm.

Synthesis and Characterization of the Bis-Benzimidazolium Salts 3
According to Scheme 1, the bis-benzimidazolium salts 3 were prepared by the combination of two equivalents of the corresponding N-arylbenzimidazole 2 and one equivalent of the desired dibromides 1 in acetonitrile under reflux to produce the respective products with yields in the range of 50 to 89%. The newly prepared salts were found to be air-and moisture-stable both in the solid state and in solution, and were characterized by 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy.
In the 1 H NMR spectra of 3a-3d, the methylene protons could be observed as a singlet, while the 1 H NMR spectra of 3e and 3f showed an AB spin system for the methylene protons. The benzimidazolium proton signals in the spectra of 3a-3f could be observed in a wide range of between δ 10.15 and 11.57 ppm. The 13 C NMR spectra of 3a-3f showed the NCHN resonances between δ 142.4 and 161.0 ppm. Scheme 1. Overview of the synthesis of bis-benzimidazolium salts 3.

The Suzuki-Miyaura Cross-Coupling Reaction
Continuing our previous studies on the application of in-situ-formed catalyst systems for the SMC reaction [28,29], 4-chloroacetophenone 4a and phenylboronic acid 5a were used as model starting materials (Table 1). Under classical conditions (K 3 PO 4 ·H 2 O, Pd(OAc) 2 , t-BuOH, 30 • C, 24 h), the activity of the L/Pd(OAc) 2 catalyst system was first compared with that of 3b/Pd(OAc) 2 (Table 1, entries 1 and 2). It was found that the xylyl-bridged bis-benzimidazolium precursor 3b showed better activity in comparison to alkyl-linked bis-benzimidazolium salt L (Table 1, entries 1 and 2). Next, the activity of the 3/Pd(OAc) 2 catalyst systems was compared. Upon increasing the reaction temperature to 80 • C, the gas chromatography (GC) yield of 6aa increased from 21% to 88% (Table 1, entries 2 and  3). The focus was shifted to investigate the influence that the xylyl-linked spacers and wingtips have on the benzimidazole ring. With the same wingtip on the benzimidazole ring (3b, 3d, and 3f), the bis-benzimidazolium precursor with a benzene ring as a xylyllinked spacer showed better activity in comparison to when pyridine or biphenyl were incorporated in the xylyl-linked bridge bis-benzimidazolium salts (Table 1, entries 3, 6, and 8). The same results were also observed using bis-benzimidazolium salts 3a, 3c, and 3e (Table 1, entries 4, 5, and 7). The activity of the bis-benzimidazolium salts with a mesityl group on the benzimidazole ring as the wingtip (3d and 3f) was better than that when a methoxyphenyl group was incorporated as a wingtip (3c and 3e), regardless of whether pyridine or biphenyl was present as the xylyl-linked bridge in the bis-benzimidazolium salts ( Table 1, entries 5-8). However, both 3a and 3b exhibited similar catalytic activity (Table 1, entries 3 and 4), an observation that shows that having a mesityl group on the benzimidazole ring leads to a sterically hindered effect, which is beneficial in the reductive elimination step of the catalytic cycle.  The effects of different solvents, bases, and Pd loading amounts on the catalytic activity of this reaction are summarized in Table 2. Most of the solvents tested gave the products in good to excellent yields (87-94%, Table 2, entries 1-4) in this work, except for a mixed solvent of t-butanol (BuOH)/H2O, the use of which led to a poor product yield (55%, Table 2, entry 5). It was observed that 1,4-dioxane was the best choice of solvent for producing products with higher conversion rates ( Table 2, entry 2). The replacement of K3PO4‧H2O with KO t Bu or KOAc led to lower GC yields of the respective products ( Table  2, entries 6 and 9) and when K2CO3 or Cs2CO3 was used instead, excellent yields were observed (Table 2, entries 7 and 8). After screening Pd loading amount, the coupling reaction could be carried out in the presence of 0.5 mol% Pd (OAc)2/3b catalyst for 6 h in 98% yield ( Table 2, entry 13). The effects of different solvents, bases, and Pd loading amounts on the catalytic activity of this reaction are summarized in Table 2. Most of the solvents tested gave the products in good to excellent yields (87-94%, Table 2, entries 1-4) in this work, except for a mixed solvent of t-butanol (BuOH)/H 2 O, the use of which led to a poor product yield (55%, Table 2, entry 5). It was observed that 1,4-dioxane was the best choice of solvent for producing products with higher conversion rates ( Table 2, entry 2). The replacement of K 3 PO 4 ·H 2 O with KO t Bu or KOAc led to lower GC yields of the respective products ( Table 2, entries 6 and 9) and when K 2 CO 3 or Cs 2 CO 3 was used instead, excellent yields were observed (Table 2, entries 7 and 8). After screening Pd loading amount, the coupling reaction could be carried out in the presence of 0.5 mol% Pd (OAc) 2 /3b catalyst for 6 h in 98% yield ( Table 2, entry 13). The scope of the SMC reaction was studied after screening the optimized reaction conditions ( Table 3). The coupling reactions of aryl chlorides 4a, 4b, and 4c with electronwithdrawing groups proceeded in quantitative yields in line with an increase in the catalyst loading and temperature (6aa-6ca). Similarly, the SMC reaction was carried out at 80 • C in the presence of the catalyst with 1.0 mol% loading using m-chloropropiophenone and p-chloropropiophenone as starting materials and quantitative yields of the desired products 6da and 6ea were obtained. With other electron-withdrawing groups at the para position, such as in 4f and 4i, 96% and 90% isolated yields were obtained, respectively (6fa and 6ia), whereas, the coupling reactions of 1-chloro-2-nitrobenzene, 4g, and 1-chloro-2,4dinitrobenzene, 4h, with phenylboronic acid showed good yields (81-89%) at 100 • C. Aryl chlorides (4a, 4d, 4e, 4f, and 4i) bearing electron-withdrawing groups at their mor ppositions were coupled with 1-naphthylboronic acid at 100 • C in the presence of a catalyst with 1.5 mol% loading to give the respective products in yield of 90-99% (6ab-6ib). It was observed that the coupling reactions of benzyl chloride with phenylboronic acid or 1-naphthylboronic acid led to 95% and 99% yields of 6ja and 6jb, respectively, under the same reaction conditions. The aryl chlorides 4k and 4l with electron-donating groups gave the corresponding products (6ka and 6la) in poor yields. Interestingly, o-chlorotoluene was coupled with phenylboronic acid in the presence of a 1 mol% 3b/Pd(OAc) 2 catalyst at 80 • C (6ma) to give the desired product in 95% yield. Finally, the di-ortho-substituted biaryl syntheses of o-nitroarenes (4n and 4g) with 1-naphthylboronic acid (5b) led to excellent yields of the respective products, with a 93% yield of 6hb and a 92% yield of 6gb observed. internal standard. 3 Isolated yield in parentheses. 4 L/Pd(OAc)2 was used. The reaction was carried out at 110 °C. 5 t-BuOH/H2O = 6/4 (vol/vol).
The scope of the SMC reaction was studied after screening the optimized reaction conditions ( Table 3). The coupling reactions of aryl chlorides 4a, 4b, and 4c with electronwithdrawing groups proceeded in quantitative yields in line with an increase in the catalyst loading and temperature (6aa-6ca). Similarly, the SMC reaction was carried out at 80 °C in the presence of the catalyst with 1.0 mol% loading using m-chloropropiophenone and p-chloropropiophenone as starting materials and quantitative yields of the desired products 6da and 6ea were obtained. With other electron-withdrawing groups at the para position, such as in 4f and 4i, 96% and 90% isolated yields were obtained, respectively (6fa and 6ia), whereas, the coupling reactions of 1-chloro-2-nitrobenzene, 4g, and 1chloro-2,4-dinitrobenzene, 4h, with phenylboronic acid showed good yields (81-89%) at 100 °C. Aryl chlorides (4a, 4d, 4e, 4f, and 4i) bearing electron-withdrawing groups at their m-or p-positions were coupled with 1-naphthylboronic acid at 100 °C in the presence of a catalyst with 1.5 mol% loading to give the respective products in yield of 90-99% (6ab-6ib). It was observed that the coupling reactions of benzyl chloride with phenylboronic acid or 1-naphthylboronic acid led to 95% and 99% yields of 6ja and 6jb, respectively, under the same reaction conditions. The aryl chlorides 4k and 4l with electron-donating groups gave the corresponding products (6ka and 6la) in poor yields. Interestingly, ochlorotoluene was coupled with phenylboronic acid in the presence of a 1 mol% 3b/Pd(OAc)2 catalyst at 80 °C (6ma) to give the desired product in 95% yield. Finally, the di-ortho-substituted biaryl syntheses of o-nitroarenes (4n and 4g) with 1-naphthylboronic acid (5b) led to excellent yields of the respective products, with a 93% yield of 6hb and a 92% yield of 6gb observed. mmol) in solvent (3.0 mL) under a N2 atmosphere. Determined by GC-FID using undecane as an internal standard. 3 Isolated yield in parentheses. 4 L/Pd(OAc)2 was used. The reaction was carried out at 110 °C. 5 t-BuOH/H2O = 6/4 (vol/vol).
The scope of the SMC reaction was studied after screening the optimized reaction conditions ( Table 3). The coupling reactions of aryl chlorides 4a, 4b, and 4c with electronwithdrawing groups proceeded in quantitative yields in line with an increase in the catalyst loading and temperature (6aa-6ca). Similarly, the SMC reaction was carried out at 80 °C in the presence of the catalyst with 1.0 mol% loading using m-chloropropiophenone and p-chloropropiophenone as starting materials and quantitative yields of the desired products 6da and 6ea were obtained. With other electron-withdrawing groups at the para position, such as in 4f and 4i, 96% and 90% isolated yields were obtained, respectively (6fa and 6ia), whereas, the coupling reactions of 1-chloro-2-nitrobenzene, 4g, and 1chloro-2,4-dinitrobenzene, 4h, with phenylboronic acid showed good yields (81-89%) at 100 °C. Aryl chlorides (4a, 4d, 4e, 4f, and 4i) bearing electron-withdrawing groups at their m-or p-positions were coupled with 1-naphthylboronic acid at 100 °C in the presence of a catalyst with 1.5 mol% loading to give the respective products in yield of 90-99% (6ab-6ib). It was observed that the coupling reactions of benzyl chloride with phenylboronic acid or 1-naphthylboronic acid led to 95% and 99% yields of 6ja and 6jb, respectively, under the same reaction conditions. The aryl chlorides 4k and 4l with electron-donating groups gave the corresponding products (6ka and 6la) in poor yields. Interestingly, ochlorotoluene was coupled with phenylboronic acid in the presence of a 1 mol% 3b/Pd(OAc)2 catalyst at 80 °C (6ma) to give the desired product in 95% yield. Finally, the di-ortho-substituted biaryl syntheses of o-nitroarenes (4n and 4g) with 1-naphthylboronic acid (5b) led to excellent yields of the respective products, with a 93% yield of 6hb and a 92% yield of 6gb observed. internal standard. 3 Isolated yield in parentheses. 4 L/Pd(OAc)2 was used. The reaction was carried out at 110 °C. 5 t-BuOH/H2O = 6/4 (vol/vol).
The scope of the SMC reaction was studied after screening the optimized reaction conditions ( Table 3). The coupling reactions of aryl chlorides 4a, 4b, and 4c with electronwithdrawing groups proceeded in quantitative yields in line with an increase in the catalyst loading and temperature (6aa-6ca). Similarly, the SMC reaction was carried out at 80 °C in the presence of the catalyst with 1.0 mol% loading using m-chloropropiophenone and p-chloropropiophenone as starting materials and quantitative yields of the desired products 6da and 6ea were obtained. With other electron-withdrawing groups at the para position, such as in 4f and 4i, 96% and 90% isolated yields were obtained, respectively (6fa and 6ia), whereas, the coupling reactions of 1-chloro-2-nitrobenzene, 4g, and 1chloro-2,4-dinitrobenzene, 4h, with phenylboronic acid showed good yields (81-89%) at 100 °C. Aryl chlorides (4a, 4d, 4e, 4f, and 4i) bearing electron-withdrawing groups at their m-or p-positions were coupled with 1-naphthylboronic acid at 100 °C in the presence of a catalyst with 1.5 mol% loading to give the respective products in yield of 90-99% (6ab-6ib). It was observed that the coupling reactions of benzyl chloride with phenylboronic acid or 1-naphthylboronic acid led to 95% and 99% yields of 6ja and 6jb, respectively, under the same reaction conditions. The aryl chlorides 4k and 4l with electron-donating groups gave the corresponding products (6ka and 6la) in poor yields. Interestingly, ochlorotoluene was coupled with phenylboronic acid in the presence of a 1 mol% 3b/Pd(OAc)2 catalyst at 80 °C (6ma) to give the desired product in 95% yield. Finally, the di-ortho-substituted biaryl syntheses of o-nitroarenes (4n and 4g) with 1-naphthylboronic acid (5b) led to excellent yields of the respective products, with a 93% yield of 6hb and a 92% yield of 6gb observed. internal standard. 3 Isolated yield in parentheses. 4 L/Pd(OAc)2 was used. The reaction was carried out at 110 °C. 5 t-BuOH/H2O = 6/4 (vol/vol).
The scope of the SMC reaction was studied after screening the optimized reaction conditions ( Table 3). The coupling reactions of aryl chlorides 4a, 4b, and 4c with electronwithdrawing groups proceeded in quantitative yields in line with an increase in the catalyst loading and temperature (6aa-6ca). Similarly, the SMC reaction was carried out at 80 °C in the presence of the catalyst with 1.0 mol% loading using m-chloropropiophenone and p-chloropropiophenone as starting materials and quantitative yields of the desired products 6da and 6ea were obtained. With other electron-withdrawing groups at the para position, such as in 4f and 4i, 96% and 90% isolated yields were obtained, respectively (6fa and 6ia), whereas, the coupling reactions of 1-chloro-2-nitrobenzene, 4g, and 1chloro-2,4-dinitrobenzene, 4h, with phenylboronic acid showed good yields (81-89%) at 100 °C. Aryl chlorides (4a, 4d, 4e, 4f, and 4i) bearing electron-withdrawing groups at their m-or p-positions were coupled with 1-naphthylboronic acid at 100 °C in the presence of a catalyst with 1.5 mol% loading to give the respective products in yield of 90-99% (6ab-6ib). It was observed that the coupling reactions of benzyl chloride with phenylboronic acid or 1-naphthylboronic acid led to 95% and 99% yields of 6ja and 6jb, respectively, under the same reaction conditions. The aryl chlorides 4k and 4l with electron-donating groups gave the corresponding products (6ka and 6la) in poor yields. Interestingly, ochlorotoluene was coupled with phenylboronic acid in the presence of a 1 mol% 3b/Pd(OAc)2 catalyst at 80 °C (6ma) to give the desired product in 95% yield. Finally, the di-ortho-substituted biaryl syntheses of o-nitroarenes (4n and 4g) with 1-naphthylboronic acid (5b) led to excellent yields of the respective products, with a 93% yield of 6hb and a 92% yield of 6gb observed. internal standard. Isolated yield in parentheses. L/Pd(OAc)2 was used. The reaction was carried out at 110 °C. 5 t-BuOH/H2O = 6/4 (vol/vol).
The scope of the SMC reaction was studied after screening the optimized reaction conditions ( Table 3). The coupling reactions of aryl chlorides 4a, 4b, and 4c with electronwithdrawing groups proceeded in quantitative yields in line with an increase in the catalyst loading and temperature (6aa-6ca). Similarly, the SMC reaction was carried out at 80 °C in the presence of the catalyst with 1.0 mol% loading using m-chloropropiophenone and p-chloropropiophenone as starting materials and quantitative yields of the desired products 6da and 6ea were obtained. With other electron-withdrawing groups at the para position, such as in 4f and 4i, 96% and 90% isolated yields were obtained, respectively (6fa and 6ia), whereas, the coupling reactions of 1-chloro-2-nitrobenzene, 4g, and 1chloro-2,4-dinitrobenzene, 4h, with phenylboronic acid showed good yields (81-89%) at 100 °C . Aryl chlorides (4a, 4d, 4e, 4f, and 4i) bearing electron-withdrawing groups at their m-or p-positions were coupled with 1-naphthylboronic acid at 100 °C in the presence of a catalyst with 1.5 mol% loading to give the respective products in yield of 90-99% (6ab-6ib). It was observed that the coupling reactions of benzyl chloride with phenylboronic acid or 1-naphthylboronic acid led to 95% and 99% yields of 6ja and 6jb, respectively, under the same reaction conditions. The aryl chlorides 4k and 4l with electron-donating groups gave the corresponding products (6ka and 6la) in poor yields. Interestingly, ochlorotoluene was coupled with phenylboronic acid in the presence of a 1 mol% 3b/Pd(OAc)2 catalyst at 80 °C (6ma) to give the desired product in 95% yield. Finally, the di-ortho-substituted biaryl syntheses of o-nitroarenes (4n and 4g) with 1-naphthylboronic acid (5b) led to excellent yields of the respective products, with a 93% yield of 6hb and a 92% yield of 6gb observed. out at 110 °C. 5 t-BuOH/H2O = 6/4 (vol/vol).
The scope of the SMC reaction was studied after screening the optimized reaction conditions ( Table 3). The coupling reactions of aryl chlorides 4a, 4b, and 4c with electronwithdrawing groups proceeded in quantitative yields in line with an increase in the catalyst loading and temperature (6aa-6ca). Similarly, the SMC reaction was carried out at 80 °C in the presence of the catalyst with 1.0 mol% loading using m-chloropropiophenone and p-chloropropiophenone as starting materials and quantitative yields of the desired products 6da and 6ea were obtained. With other electron-withdrawing groups at the para position, such as in 4f and 4i, 96% and 90% isolated yields were obtained, respectively (6fa and 6ia), whereas, the coupling reactions of 1-chloro-2-nitrobenzene, 4g, and 1chloro-2,4-dinitrobenzene, 4h, with phenylboronic acid showed good yields (81-89%) at 100 °C. Aryl chlorides (4a, 4d, 4e, 4f, and 4i) bearing electron-withdrawing groups at their m-or p-positions were coupled with 1-naphthylboronic acid at 100 °C in the presence of a catalyst with 1.5 mol% loading to give the respective products in yield of 90-99% (6ab-6ib). It was observed that the coupling reactions of benzyl chloride with phenylboronic acid or 1-naphthylboronic acid led to 95% and 99% yields of 6ja and 6jb, respectively, under the same reaction conditions. The aryl chlorides 4k and 4l with electron-donating groups gave the corresponding products (6ka and 6la) in poor yields. Interestingly, ochlorotoluene was coupled with phenylboronic acid in the presence of a 1 mol% 3b/Pd(OAc)2 catalyst at 80 °C (6ma) to give the desired product in 95% yield. Finally, the di-ortho-substituted biaryl syntheses of o-nitroarenes (4n and 4g) with 1-naphthylboronic acid (5b) led to excellent yields of the respective products, with a 93% yield of 6hb and a 92% yield of 6gb observed. out at 110 °C. 5 t-BuOH/H2O = 6/4 (vol/vol).
The scope of the SMC reaction was studied after screening the optimized reaction conditions ( Table 3). The coupling reactions of aryl chlorides 4a, 4b, and 4c with electronwithdrawing groups proceeded in quantitative yields in line with an increase in the catalyst loading and temperature (6aa-6ca). Similarly, the SMC reaction was carried out at 80 °C in the presence of the catalyst with 1.0 mol% loading using m-chloropropiophenone and p-chloropropiophenone as starting materials and quantitative yields of the desired products 6da and 6ea were obtained. With other electron-withdrawing groups at the para position, such as in 4f and 4i, 96% and 90% isolated yields were obtained, respectively (6fa and 6ia), whereas, the coupling reactions of 1-chloro-2-nitrobenzene, 4g, and 1chloro-2,4-dinitrobenzene, 4h, with phenylboronic acid showed good yields (81-89%) at 100 °C. Aryl chlorides (4a, 4d, 4e, 4f, and 4i) bearing electron-withdrawing groups at their m-or p-positions were coupled with 1-naphthylboronic acid at 100 °C in the presence of a catalyst with 1.5 mol% loading to give the respective products in yield of 90-99% (6ab-6ib). It was observed that the coupling reactions of benzyl chloride with phenylboronic acid or 1-naphthylboronic acid led to 95% and 99% yields of 6ja and 6jb, respectively, under the same reaction conditions. The aryl chlorides 4k and 4l with electron-donating groups gave the corresponding products (6ka and 6la) in poor yields. Interestingly, ochlorotoluene was coupled with phenylboronic acid in the presence of a 1 mol% 3b/Pd(OAc)2 catalyst at 80 °C (6ma) to give the desired product in 95% yield. Finally, the di-ortho-substituted biaryl syntheses of o-nitroarenes (4n and 4g) with 1-naphthylboronic acid (5b) led to excellent yields of the respective products, with a 93% yield of 6hb and a 92% yield of 6gb observed. internal standard. Isolated yield in parentheses. L/Pd(OAc)2 was used. The reaction was carried out at 110 °C. 5 t-BuOH/H2O = 6/4 (vol/vol).
The scope of the SMC reaction was studied after screening the optimized reaction conditions ( Table 3). The coupling reactions of aryl chlorides 4a, 4b, and 4c with electronwithdrawing groups proceeded in quantitative yields in line with an increase in the catalyst loading and temperature (6aa-6ca). Similarly, the SMC reaction was carried out at 80 °C in the presence of the catalyst with 1.0 mol% loading using m-chloropropiophenone and p-chloropropiophenone as starting materials and quantitative yields of the desired products 6da and 6ea were obtained. With other electron-withdrawing groups at the para position, such as in 4f and 4i, 96% and 90% isolated yields were obtained, respectively (6fa and 6ia), whereas, the coupling reactions of 1-chloro-2-nitrobenzene, 4g, and 1chloro-2,4-dinitrobenzene, 4h, with phenylboronic acid showed good yields (81-89%) at 100 °C . Aryl chlorides (4a, 4d, 4e, 4f, and 4i) bearing electron-withdrawing groups at their m-or p-positions were coupled with 1-naphthylboronic acid at 100 °C in the presence of a catalyst with 1.5 mol% loading to give the respective products in yield of 90-99% (6ab-6ib). It was observed that the coupling reactions of benzyl chloride with phenylboronic acid or 1-naphthylboronic acid led to 95% and 99% yields of 6ja and 6jb, respectively, under the same reaction conditions. The aryl chlorides 4k and 4l with electron-donating groups gave the corresponding products (6ka and 6la) in poor yields. Interestingly, ochlorotoluene was coupled with phenylboronic acid in the presence of a 1 mol% 3b/Pd(OAc)2 catalyst at 80 °C (6ma) to give the desired product in 95% yield. Finally, the di-ortho-substituted biaryl syntheses of o-nitroarenes (4n and 4g) with 1-naphthylboronic acid (5b) led to excellent yields of the respective products, with a 93% yield of 6hb and a 92% yield of 6gb observed. out at 110 °C. 5 t-BuOH/H2O = 6/4 (vol/vol).
The scope of the SMC reaction was studied after screening the optimized reaction conditions ( Table 3). The coupling reactions of aryl chlorides 4a, 4b, and 4c with electronwithdrawing groups proceeded in quantitative yields in line with an increase in the catalyst loading and temperature (6aa-6ca). Similarly, the SMC reaction was carried out at 80 °C in the presence of the catalyst with 1.0 mol% loading using m-chloropropiophenone and p-chloropropiophenone as starting materials and quantitative yields of the desired products 6da and 6ea were obtained. With other electron-withdrawing groups at the para position, such as in 4f and 4i, 96% and 90% isolated yields were obtained, respectively (6fa and 6ia), whereas, the coupling reactions of 1-chloro-2-nitrobenzene, 4g, and 1chloro-2,4-dinitrobenzene, 4h, with phenylboronic acid showed good yields (81-89%) at 100 °C . Aryl chlorides (4a, 4d, 4e, 4f, and 4i) bearing electron-withdrawing groups at their m-or p-positions were coupled with 1-naphthylboronic acid at 100 °C in the presence of a catalyst with 1.5 mol% loading to give the respective products in yield of 90-99% (6ab-6ib). It was observed that the coupling reactions of benzyl chloride with phenylboronic acid or 1-naphthylboronic acid led to 95% and 99% yields of 6ja and 6jb, respectively, under the same reaction conditions. The aryl chlorides 4k and 4l with electron-donating groups gave the corresponding products (6ka and 6la) in poor yields. Interestingly, ochlorotoluene was coupled with phenylboronic acid in the presence of a 1 mol% 3b/Pd(OAc)2 catalyst at 80 °C (6ma) to give the desired product in 95% yield. Finally, the di-ortho-substituted biaryl syntheses of o-nitroarenes (4n and 4g) with 1-naphthylboronic acid (5b) led to excellent yields of the respective products, with a 93% yield of 6hb and a 92% yield of 6gb observed.