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Article

Pd-Catalyzed, Highly Selective C(sp2)-Br Bond Coupling Reactions of o-(or m-, or p-) Chloromethyl Bromobenzene with Arylboronic Acids

by
Ming-ming Pei
,
Ping Liu
*,
Yan Liu
,
Xin-ming Lv
,
Xiao-wei Ma
* and
Bin Dai
School of Chemistry and Chemical Engineering/Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, Shihezi 832003, China
*
Authors to whom correspondence should be addressed.
Molecules 2018, 23(2), 433; https://doi.org/10.3390/molecules23020433
Submission received: 25 January 2018 / Revised: 13 February 2018 / Accepted: 13 February 2018 / Published: 15 February 2018
(This article belongs to the Special Issue Palladium Catalysts 2018)
Browse Figures
Versions Notes

Abstract

:
Highly selective C(sp2)–C(sp2) cross-coupling of dihalogenated hydrocarbons comprising C(sp2)–Br and C(sp3)–Cl bonds with arylboronic acids is reported. This highly selective coupling reaction of the C(sp2)–Br bond is successfully achieved using Pd(OAc)2 and PCy3·HBF4 as the palladium source and ligand, respectively. A series of chloromethyl-1,1′-biphenyl compounds are obtained in moderate-to-excellent yields. Moreover, this protocol can be extended to the one-pot dual arylation of 1-bromo-4-(chloromethyl)benzene with two arylboronic acids, leading to diverse unsymmetrical 4-benzyl-1,1′-biphenyl derivatives.

Graphical Abstract

1. Introduction

Transition-metal-catalyzed cross-coupling reactions between electrophiles and arylboronic acids are an important method in the C–C bond formation [1,2,3]. Over the past decades, aryl and benzyl halides have been used as electrophiles for constructing C(sp2)–C(sp2) and C(sp3)–C(sp2) bonds, respectively [4,5,6,7,8,9,10]. To the best of our knowledge, the selective reaction of dihalogenated hydrocarbons containing the C(sp2)–X and C(sp3)–X bonds with arylboronic acids in the presence of palladium catalyst has been rarely reported [11,12,13,14,15,16]. Duchêne and Thibonnet reported the Pd(PPh3)4-catalyzed selective coupling reaction of C(sp3)–Br at the benzylic position of the starting bromobenzyl bromides with arylboronic acids, affording C(sp3)–C(sp2) as the coupling products (Scheme 1a) [11,12]. Gueiffier also developed a Pd(PPh3)4-catalyzed one-pot two-step reaction of bromobenzyl chloride with arylboronic acids by first C(sp3)–C(sp2) coupling and subsequent C(sp2)–C(sp2) coupling, affording numerous new unsymmetrical methylene-linked biaryl systems (Scheme 1a)[13]. Çetinkaya et al. achieved the palladium-catalyzed C(sp2)–C(sp2) coupling reactions with 1-bromo-4-(bromomethyl)benzene and arylboronic acids by using saturated N-heterocarbene ligands [17]. In 2010, Maseras conducted an experimental and theoretical study on the role of phosphine ligands in palladium-catalyzed Suzuki cross-coupling of competitive and selective C(sp3)–Br versus C(sp2)–Br bond activation [18]. Their results indicated that as a less-hindered phosphine, PPh3 is associated with a bisligated form of the catalyst, which favors the activation of the C(sp3)–Br bond of the α-bromosulfoxide side. As the more hindered phosphine, P(1-napthyl)3 is related to the monoligated form of the catalyst, which promotes the activation of the C(sp2)–Br bond of the bromoaryl moiety.
Inspired by this study and based on our previous studies [19,20,21,22,23,24,25], we reported Pd-catalyzed, highly selective C(sp2)-Br bond coupling reactions of o-(or m-, or p-)chloromethyl bromobenzene with arylboronic acids in the presence of the ligand PCy3·HBF4, which does not afford C(sp3)–C(sp2) coupling products; instead, the reaction provided highly selective of C(sp2)–C(sp2) coupling products (Scheme 1b).

2. Results and Discussion

Initially, 1-bromo-4-(chloromethyl)benzene and p-tolylboronic acid were selected as model substrates to optimize the reaction conditions. Table 1 summarizes the results obtained. The screened bases were examined by using PCy3·HBF4 and Pd(OAc)2 as the ligand and palladium source, respectively, in toluene/water (1/0.1) at 80 °C for 2 h; Cs2CO3 was the most effective base, affording the desired product in 99% yield (entry 5). On the other hand, other bases such as K2CO3, K3PO4·3H2O, NaOH, and NEt3 afforded the desired products in 16–84% yields (entries 1–4). Remarkably, the ligand was found to play an important role in this reaction, and PPh3 was not effective for this selective C(sp2)–C(sp2) coupling reaction (entry 6). Moreover, with the decrease in the reaction temperature to 60 °C, the product was obtained in only 74% yield (entry 7). With the decrease in the catalyst amount from 1 mol % to 0.2 mol %, the desired product was still obtained in a gas chromatography-mass spectrometer (GC–MS) yield of 99% (entries 8–10). However, with the decrease in the catalyst loading to 0.1 mol %, the yield was significantly reduced (entry 11). Finally, the combination of Pd(OAc)2 (0.2 mol %)/PCy3·HBF4 (0.4 mol %) and Cs2CO3 (2 equiv.) at 80 °C for 2 h in toluene/water (1 mL/0.1 mL) was found to constitute the optimum reaction conditions.
With the optimized reaction conditions in hand, the substrate scope of this selective Suzuki–Miyaura reaction was examined. First, the coupling reactions of 1-bromo-4-(chloromethyl)benzene with arylboronic acid were explored under the optimized reaction conditions. 4-Substituted arylboronic acids bearing electron-donating or electron-withdrawing groups selectively underwent the coupling reaction, affording corresponding products 3b–3g in 75–93% yields (Table 2). Furthermore, the selective coupling reaction of 1-bromo-4-(chloromethyl)benzene, with m-tolylboronic acid, and (3-chlorophenyl)boronic acid afforded the desired products 3h and 3i in 98% and 73% yields, respectively. Sterically demanding ortho substituents, such as o-tolylboronic acid, did not impair the coupling reaction, affording the desired product 3j in 90% yield. However, (2,3-difluorophenyl)boronic acid and (2,6-dimethylphenyl)boronic acid as substrates afforded coupling products 3k and 3l, respectively, in low yields. In addition, thiophen-3-ylboronic acid, naphthalen-2-ylboronic acid, and 4-vinylphenylboronic acid were tolerated, affording desired products 3n–3p in 57–86% yields.
Next, the selective coupling reactions of 1-bromo-3-(chloromethyl)benzene with various arylboronic acids were investigated (Table 3). The results indicated that neither the electronic property nor the steric hindrance of the substrates clearly affects the coupling reaction: The desired products 4a–4h were obtained in 73–95% yields.
To further ascertain the application scope of the catalytic system, the reaction of 1-bromo-2-(chloromethyl)benzene with arylboronic acids was examined. The present catalytic method can be applied for the selective coupling of 1-bromo-2-(chloromethyl)benzene with arylboronic acids, affording the desired products 5a–5h in yields of 80–95% (Table 4).
A one-pot dual Suzuki coupling reaction for successively substituting 4-bromobenzyl chloride with distinct aryl groups was contemplated, which could provide a straightforward route for obtaining diverse 4-benzyl-1,1′-biphenyl derivatives (Table 5). First, 4-bromobenzyl chloride was treated with 1.1 equivalent of p-tolylboronic acid in the presence of 2 mol % of Pd(OAc)2, 0.4 mol % of PCy3·HBF4, and 5.0 equiv. of Cs2CO3 in a mixture of toluene and water (10:1). After heating for 2 h at 80 °C, 1.0 equivalent of arylboronic acid and 4.0 mol % of PPh3 were added to the reaction system. The reaction mixture was stirred for 5 h at 80 °C, affording the desired products 6a–6d in 57–96% yields.
Next, the coupling reactions of 1-bromo-4-(bromomethyl)benzene (1d) with p-tolylboronic acid (2a) were investigated under the optimized conditions. We found that the selective reaction of C(sp2)–Br bond with arylboronic acids could proceed smoothly to give 42% of the desired product 7a, also accompanied by 25% yield of bis-coupling product 7b (Scheme 2). This experimental result shows that the selectivity of the reaction depends not only on the regulatory effect of the phosphine ligand but also on the structure of the C(sp3)–X bond.
The selectivity depended exclusively on the palladium ligands.
To demonstrate the importance of phosphine ligand for palladium-catalyzed selective coupling reactions of C(sp2)–Br bond or C(sp3)–Cl bond with arylboronic acid, the external competition experiment was performed. To this end, we designed an experiment in which mixtures of bromobenzene and (chloromethyl)benzene were allowed to react with p-tolylboronic acid (Scheme 3). As expected, the formation of the Csp2–Csp2 cross-coupling product (7c) was achieved in the competitive experiment when PCy3∙HBF4 was used as the phosphine ligand in the palladium catalyst.

3. Materials and Methods

Chemicals were obtained commercially and used as received. Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker DPX–400 spectrometer (Bruker Co., Billerica, MA, USA) using tetramethylsilane (TMS) as the internal standard. Electric impact ionization (EI)–Mass spectrum was measured on a gas chromatography time of flight high resolution mass spectrometry (GCTOF-HRMS) (Waters Co, Milford, MA, USA). or GC-MS (Agilent 7890A/5975C, Santa Clara, CA, USA) instrument. Electrospray ionization (ESI)–Mass spectrum was measured on a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) (Bruker Co., Bremen, Germany). To all copies of 1H NMR, 13C NMR and HRMS spectra, please see Figures S2–S45 in Supplementary Materials. All products were isolated by short chromatography on a silica gel (200–300 mesh) column using petroleum ether (60–90 °C), unless otherwise noted. Arylboronic acids and o-(or m-, or p-)chloromethyl bromobenzene were of analytical grade quality, purchased from Adamas-beta Pharmaceuticals, Inc. (Shanghai, China).

3.1. General Procedure for the Selective Coupling Reaction of o-(or m-, or p-)chloromethyl Bromobenzene with Arylboronic Acid

A Schlenk tube (20 mL) was charged with o-(or m-, or p-)chloromethyl bromobenzene (0.3 mmol), arylboronic acid (0.33 mmol), Pd(OAc)2 (0.2 mol %), PCy3·HBF4 (0.4 mol %), and Cs2CO3 (2 equiv.). The tube was degassed for 30 s and then was filled with argon. This operation was repeated three times. After toluene (1.0 mL) and H2O (0.1 mL) were added under argon atmosphere, the resulting reaction mixture was stirred at 80 °C for 2 h under argon. After the completion of the reaction, the reaction mixture was allowed to cool to room temperature. The solution was quenched with water (10 mL) and extracted with EtOAc (3 × 10 mL). The combined EtOAc extracts were dried over anhydrous Na2SO4 and filtered, followed by solvent removal under reduced pressure. The residue was purified by flash column chromatography on silica gel using petroleum ether/EtOAc as the eluent.

3.2. General Procedure for One-Pot Dual Arylations of 1-Bromo-4-(chloromethyl)benzene

A Schlenk tube (20 mL) was charged with 1-bromo-4-(chloromethyl)benzene (0.3 mmol), arylboronic acid (0.33 mmol), 2 mol % Pd(OAc)2, 0.4 mol % PCy3·HBF4, and 5 equiv. Cs2CO3. The tube was degassed for 30 s and then was filled with argon. This operation was repeated for three times. After toluene (1.0 mL) and H2O (0.1 mL) were added under argon atmosphere, the resulting reaction mixture was stirred at 80 °C for 2 h under argon. After the completion of the reaction, the solution was allowed to cool to room temperature. Then, another arylboronic acid (0.33 mmol) and 4 mol % PPh3 were introduced under argon. The reaction mixture was heated at 80 °C for 5 h. The solution was quenched with water (10 mL) and extracted with EtOAc (3 × 10 mL). The combined EtOAc extracts were dried over anhydrous Na2SO4, filtrated, and then the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel with PE/EtOAc as the eluent.
4-(chloromethyl)-4′-methyl-1,1′-biphenyl (3a) [26]: Colorless oil (64.3 mg, 99%). 1H-NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 4.63 (s, 2H), 2.40 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 141.48, 137.75, 137.53, 136.28, 129.69, 129.18, 127.43, 127.10, 46.27, 21.27.
4-(chloromethyl)-1,1′-biphenyl (3b) [27]: Yellow oil (47.9 mg, 79%). 1H-NMR (400 MHz, CDCl3) δ 7.58 (d, J = 7.2 Hz, 4H), 7.51–7.40 (m, 4H), 7.39–7.32 (m, 1H), 4.63 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 141.53, 140.63, 136.58, 129.19, 128.96, 127.67, 127.63, 127.26, 46.19.
4-(chloromethyl)-4′-methoxy-1,1′-biphenyl (3c) [28]: Colorless oil (60.7 mg, 87%). 1H-NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 4.63 (s, 2H), 3.85 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 159.50, 141.16, 135.94, 133.15, 129.19, 128.29, 127.17, 114.41, 55.51, 46.30.
4-(chloromethyl)-4′-propyl-1,1′-biphenyl (3d): Colorless oil (60.9 mg, 83%). 1H-NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.26 (s, 1H), 7.24 (d, J = 2.8 Hz, 1H), 4.63 (s, 2H), 2.65–2.60 (m, 2H), 1.68 (dq, J = 14.8, 7.2 Hz, 2H), 0.97 (t, J = 7.3 Hz, 3H). 13C-NMR (100 MHz, CDCl3) δ 142.33, 141.51, 137.97, 136.24, 129.16, 129.09, 127.44, 127.07, 46.27, 37.84, 24.69, 14.03. HRMS (ESI) m/z calcd for C16H17ClNa+ (M + Na)+ 267.09110, found 267.09195.
4-(chloromethyl)-4′-pentyl-1,1′-bipheny (3e) [29]: White solid (75.8 mg, 93%). 1H-NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.26 (s, 1H), 7.25 (d, J = 3.2 Hz, 1H), 4.63 (s, 2H), 2.67–2.61 (m, 2H), 1.65 (p, J = 7.4 Hz, 2H), 1.39–1.32 (m, 4H), 0.93–0.88 (m, 3H). 13C-NMR (100 MHz, CDCl3) δ 142.60, 141.51, 137.93, 136.24, 129.16, 129.03, 127.44, 127.09, 46.28, 35.73, 31.70, 31.31, 22.71, 14.19.
4-(chloromethyl)-4′-fluoro-1,1′-biphenyl (3f) [30]: Colorless oil (54.9 mg, 83%). 1H-NMR (400 MHz, CDCl3) δ 7.55 (d, J = 3.2 Hz, 1H), 7.54–7.51 (m, 3H), 7.45 (d, J = 8.0 Hz, 2H), 7.12 (t, J = 8.8 Hz, 2H), 4.63 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 162.74, 140.53, 136.63, 129.41, 129.25, 128.82, 127.48, 115.85, 46.10.
4-(chloromethyl)-4′-(trifluoromethyl)-1,1′-biphenyl (3g) [31]: Colorless oil (60.9 mg, 75%). 1H-NMR (400 MHz, CDCl3) δ 7.69 (d, J = 1.6 Hz, 4H), 7.59 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 4.64 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 144.14, 140.03, 137.63, 129.95–129.57 (m), 129.39, 127.79, 127.55, 125.93 (q, J = 4.0 Hz),123.78 (dd, J =420.0, 271.0 Hz) 45.94.
4′-(chloromethyl)-3-methyl-1,1′-biphenyl (3h): Colorless oil (63.7 mg, 98%). 1H-NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.8 Hz, 2H), 7.31 (t, J = 7.6 Hz, 1H), 7.16 (d, J = 7.6 Hz, 1H), 4.61 (s, 2H), 2.40 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 141.61, 140.59, 138.52, 136.45, 129.11, 128.85, 128.40, 128.02, 127.59, 124.35, 46.20, 21.66. HRMS (EI): m/z calcd for C14H13Cl [M]: 216.0723, found [M]: 216.0723.
3-chloro-4′-(chloromethyl)-1,1′-biphenyl (3i): Colorless oil (51.9 mg, 73%). 1H-NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.4 Hz, 3H), 7.47–7.42 (m, 3H), 7.38–7.30 (m, 2H), 4.62 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 142.42, 140.02, 137.24, 134.84, 130.18, 129.28, 127.66, 127.56, 127.35, 125.37, 45.99. HRMS (EI): m/z calcd for C13H10Cl2 [M]: 236.0169, found [M]: 236.0160.
4′-(chloromethyl)-2-methyl-1,1′-biphenyl (3j) [32]: Colorless oil (58.5 mg, 90%). 1H-NMR (400 MHz, CDCl3) δ 7.43 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.28–7.25 (m, 2H), 7.25–7.19 (m, 2H), 4.64 (s, 2H), 2.27 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 142.29, 141.35, 136.06, 135.44, 130.52, 129.86, 129.71, 128.49, 127.60, 125.97, 46.28, 20.59.
4′-(chloromethyl)-2,3-difluoro-1,1′-biphenyl (3k): Yellow oil (33.6 mg, 47%). 1H-NMR (400 MHz, CDCl3) δ 7.54 (d, J = 6.8 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.21–7.08 (m, 3H), 4.63 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 151.25 (dd, J = 247.0, 14.0 Hz), 148.12 (dd, J = 249.0, 14.0 Hz), 137.55, 134.96 (d, J = 4.0 Hz), 130.75 (d, J = 10.0 Hz), 129.45 (d, J = 3.0 Hz), 128.95, 125.46–125.27 (m), 124.29 (dd, J = 7.0, 5.0 Hz), 116.46 (d, J = 20.0 Hz), 45.96. HRMS (EI): m/z calcd for C13H9ClF2 [M]: 238.0369, found [M]: 238.0361.
4′-(chloromethyl)-2,6-dimethyl-1,1′-biphenyl (3l): Colorless oil (34.6 mg, 50%). 1H-NMR (400 MHz, CDCl3) δ 7.44 (d, J = 8.0 Hz, 2H), 7.15 (t, J = 2.9 Hz, 2H), 7.13 (s, 1H), 7.10 (d, J = 7.6 Hz, 2H), 4.65 (s, 2H), 2.02 (s, 6H). 13C-NMR (100 MHz, CDCl3) δ 140.29, 139.54, 137.04, 132.09, 129.33, 128.84, 127.43, 122.00, 46.05, 29.85. HRMS (ESI) m/z calcd for C15H16Cl+ (M + H)+ 231.09350, found 231.09262.
4′-(chloromethyl)-3,4,5-trifluoro-1,1′-biphenyl (3m) [33]: Colorless oil (56.2 mg, 73%). 1H-NMR (400 MHz, CDCl3) δ 7.48 (d, J = 1.6 Hz, 4H), 7.17 (dd, J = 6.4, 6.4 Hz, 2H), 4.62 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 151.60 (ddd, J = 248.0, 10.0, 4.0 Hz), 141.05–138.04 (m), 138.43, 137.88, 136.74 (td, J = 7.7, 4.6 Hz), 129.46, 127.3, 111.34–111.04 (m), 45.77.
3-(4-(chloromethyl)phenyl)thiophene (3n) [34]: Colorless oil (48.2 mg, 77%). 1H-NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.4 Hz, 2H), 7.45 (dd, J = 1.6, 1.6 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 1.2 Hz, 1H), 7.37 (s, 1H), 4.60 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 141.78, 136.3, 136.13, 129.26, 126.88, 126.52, 126.38, 120.84, 46.21.
2-(4-(chloromethyl)phenyl)naphthalene (3o) [35]: Colorless oil (65.2 mg, 86%). 1H-NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.90–7.82 (m, 3H), 7.71–7.66 (m, 3H), 7.51–7.44 (m, 4H), 4.62 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 141.43, 137.93, 136.68, 133.76, 132.86, 129.30, 128.66, 128.36, 127.89, 127.79, 126.53, 126.24, 126.02, 125.53, 46.21.
4-(chloromethyl)-4′-vinyl-1,1′-biphenyl (3p): Colorless oil (39.1 mg, 57%). 1H-NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H), 7.49 (s, 1H), 7.47 (d, J = 2.8 Hz, 2H), 7.45 (s, 1H), 6.76 (dd, J = 10.8, 10.8 Hz, 1H), 5.80 (d, J = 17.6 Hz, 1H), 5.28 (d, J = 10.8 Hz, 1H), 4.64 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 140.98, 139.91, 137.00, 136.62, 136.44, 129.21, 127.39, 127.31, 126.83, 114.24, 46.17. HRMS (ESI) m/z calcd for C15H13ClNa+ (M + Na)+ 251.05980, found 251.06100.
3-(chloromethyl)-1,1′-biphenyl (4a) [36]: Yellow solid (57.8 mg, 95%). 1H-NMR (400 MHz, CDCl3) δ 7.62–7.59 (m, 2H), 7.58 (d, J = 0.8 Hz, 1H), 7.55 (dd, J = 7.6, 1.2 Hz, 1H), 7.47–7.41 (m, 3H), 7.38 (s, 1H), 7.36 (d, J = 1.6 Hz, 1H), 4.65 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 141.96, 140.73, 138.10, 129.32, 128.96, 127.69, 127.56, 127.54, 127.36, 127.31, 46.41.
3-(chloromethyl)-4′-methyl-1,1′-biphenyl (4b) [36]: Colorless oil (58.5 mg, 90%). 1H-NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.40 (t, J = 7.6 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.24 (d, J = 7.6 Hz, 2H), 4.62 (s, 2H), 2.38 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 141.87, 138.04, 137.83, 137.50, 129.67, 129.27, 127.35, 127.26, 127.16, 127.13, 46.46, 21.25.
3-(chloromethyl)-4′-(trifluoromethyl)-1,1′-biphenyl (4c) [37]: Colorless oil (74.7 mg, 92%). 1H-NMR (400 MHz, CDCl3) δ 7.70–7.64 (m, 4H), 7.59 (s, 1H), 7.52 (dt, J = 7.4, 1.6 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 4.63 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 144.23, 140.49, 138.44, 129.78 (d, J = 32.0 Hz), 129.57, 128.45, 127.63, 127.60, 127.46, 125.91 (q, J = 4.0 Hz), 124.38 (q, J = 270.0 Hz), 46.15.
3-(chloromethyl)-3′-methyl-1,1′-biphenyl (4d): Colorless oil (60.4 mg, 93%). 1H-NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.40 (q, J = 7.6 Hz, 3H), 7.33 (dd, J = 13.6, 5.6 Hz, 2H), 7.17 (d, J = 7.2 Hz, 1H), 4.63 (s, 2H), 2.41 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 142.06, 140.70, 138.55, 138.02, 129.24, 128.85, 128.42, 128.08, 127.55, 127.44, 127.36, 124.40, 46.43, 1.66. GC-MS (m/z): 217.
3-chloro-3′-(chloromethyl)-1,1′-biphenyl (4e): Colorless oil (65.4 mg, 92%). 1H-NMR (400 MHz, CDCl3) δ 7.55 (d, J = 4.0 Hz, 2H), 7.49 (d, J = 7.2 Hz, 1H), 7.44 (d, J = 7.2 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.39–7.34 (m, 2H), 7.33–7.31 (m, 1H), 4.62 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 142.56, 140.55, 138.32, 134.87, 130.20, 129.48, 128.14, 127.71, 127.50, 127.45, 127.31, 125.47, 46.23. HRMS (EI): m/z calcd for C13H10Cl2 [M]: 236.0172, found [M]: 236.0160.
3′-(chloromethyl)-2-methyl-1,1′-biphenyl (4f) [32]: Colorless oil (56.6 mg, 87%). 1H-NMR (400 MHz, CDCl3) δ 7.36 (dd, J = 12.4, 7.2 Hz, 3H), 7.27 (d, J = 9.6 Hz, 3H), 7.22 (t, J = 5.4 Hz, 2H), 4.61 (s, 2H), 2.26 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 142.59, 141.37, 137.43, 135.41, 130.50, 129.84, 129.54, 129.36, 128.60, 127.61, 127.07, 125.95, 46.38, 20.56.
3-(3-(chloromethyl)phenyl)thiophene (4g) [32]: Colorless oil (59.5 mg, 95%). 1H-NMR (400 MHz, CDCl3) δ 7.61 (s, 1H), 7.55 (dt, J = 7.6, 1.6 Hz, 1H), 7.47 (dd, J = 2.4, 2.0 Hz, 2H), 7.43–7.34 (m, 4H), 7.31 (d, J = 8.0 Hz, 1H), 4.62 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 141.83, 138.13, 136.52, 129.35, 127.38, 126.79, 126.61, 126.52, 126.39, 120.86, 46.35.
2-(3-(chloromethyl)phenyl)naphthalene (4h): Yellow oil (55.3 mg, 73%). 1H-NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.89 (t, J = 7.2 Hz, 2H), 7.85 (d, J = 7.2 Hz, 1H), 7.71 (d, J = 6.4 Hz, 2H), 7.65 (d, J = 7.6 Hz, 1H), 7.52–7.46 (m, 2H), 7.44 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 7.6 Hz, 1H), 4.66 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 141.86, 138.22, 138.03, 133.76, 132.86, 129.43, 128.66, 128.35, 127.79, 127.64, 126.53, 126.24, 126.07, 125.58, 46.44. HRMS (EI): m/z calcd for C17H10Cl [M]: 252.0723, found [M]: 252.0706.
2-(chloromethyl)-1,1′-biphenyl (5a) [38]: Yellow oil (58.9 mg, 97%). 1H-NMR (400 MHz, CDCl3) δ 7.55–7.51 (m, 1H), 7.44 (d, J = 8.8 Hz, 1H), 7.42–7.33 (m, 6H), 7.27 (d, J = 9.2 Hz, 1H), 4.52 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 142.21, 140.31, 135.05, 130.64, 130.46, 129.28, 128.64, 128.44, 128.07, 127.59, 44.60.
2-(chloromethyl)-4′-methyl-1,1′-biphenyl (5b) [39]: Yellow oil (61.7 mg, 95%). 1H-NMR (400 MHz, CDCl3) δ 7.55–7.50 (m, 1H), 7.38–7.33 (m, 2H), 7.31 (d, J = 8.2 Hz, 2H), 7.28–7.22 (m, 3H), 4.53 (s, 2H), 2.41 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 142.19, 137.38, 137.29, 135.08, 130.61, 130.50, 129.15, 129.13, 128.61, 127.86, 44.68, 21.33.
2-(chloromethyl)-4′-(trifluoromethyl)-1,1′-biphenyl (5c) [39]: Colorless oil (72.3 mg, 89%). 1H-NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 7.6 Hz, 3H), 7.46–7.38 (m, 2H), 7.27 (d, J = 10.0 Hz, 1H), 4.48 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 143.98, 140.80, 135.04, 130.92, 130.28,129.89 (dt, J = 95.0, 30 Hz), 129.68, 128.91, 128.79, 125.43 (q, J = 4.0 Hz), 124.34 (q, J = 270.0 Hz), 44.25.
2-(chloromethyl)-3′-methyl-1,1′-biphenyl (5d) [39]: Yellow oil (59.8 mg, 92%). 1H-NMR (400 MHz, CDCl3) δ 7.56–7.51 (m, 1H), 7.38–7.34 (m, 2H), 7.31 (d, J = 7.2 Hz, 1H), 7.29–7.25 (m, 1H), 7.21 (d, J = 6.8 Hz, 5H), 4.53 (s, 2H), 2.41 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 142.32, 140.25, 138.06, 135.03, 130.58, 130.40, 130.03, 128.56, 128.31, 128.29, 127.95, 126.33, 44.64, 21.62.
3′-chloro-2-(chloromethyl)-1,1′-biphenyl (5e) [39]: Yellow oil (62.3 mg, 88%). 1H-NMR (400 MHz, CDCl3) δ 7.53 (dd, J = 7.6, 2.0 Hz, 1H), 7.40 (d, J = 1.2 Hz, 1H), 7.38 (dd, J = 4.8, 1.6 Hz, 1H), 7.37–7.32 (m, 3H), 7.32–7.29 (m, 1H), 7.25–7.22 (m, 1H), 4.49 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 142.04, 140.74, 135.02, 134.33, 130.76, 130.29, 129.67, 129.37, 128.78, 128.55, 127.79, 127.49, 44.31.
2-(chloromethyl)-2′-methyl-1,1′-biphenyl (5f) [40]: Colorless oil (56.5 mg, 87%). 1H-NMR (400 MHz, CDCl3) δ 7.55 (d, J = 6.8 Hz, 1H), 7.42–7.30 (m, 3H), 7.30–7.20 (m, 3H), 7.20–7.11 (m, 2H), 4.43–4.26 (m, 2H), 2.07 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 141.57, 139.60, 136.16, 135.41, 130.17, 130.09, 129.69, 128.41, 128.01, 127.92, 125.64, 44.26, 20.30.
3-(2-(chloromethyl)phenyl)thiophene (5g) [41]: Colorless oil (59.4 mg, 95%). 1H-NMR (400 MHz, CDCl3) δ 7.51 (dd, J = 7.2 3.6 Hz, 1H), 7.42 (dd, J = 2.8, 1.2 Hz, 1H), 7.39 (dd, J = 5.2, 3.2 Hz, 1H), 7.35 (d, J = 3.2 Hz, 3H), 7.26–7.22 (m, 1H), 4.58 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 140.44, 136.90, 135.18, 130.92, 130.41, 128.98, 128.80, 128.08, 125.76, 123.44, 44.95.
2-(2-(chloromethyl)phenyl)naphthalene (5h) [42]: Yellow oil (60.6 mg, 80%). 1H-NMR (400 MHz, CDCl3) δ 7.90–7.83 (m, 4H), 7.57–7.51 (m, 2H), 7.51–7.46 (m, 2H), 7.38 (dd, J = 2.8, 2.0 Hz, 1H), 7.37–7.33 (m, 2H), 4.54 (s, 2H). 13C-NMR (100 MHz, CDCl3) δ 142.13, 137.76, 135.26, 133.28, 130.72, 130.66, 128.68, 128.29, 128.16, 128.04, 127.84, 127.49, 126.54
4-benzyl-4′-methyl-1,1′-biphenyl (6a) [43]: Yellow oil (60.4 mg, 78%). 1H-NMR (400 MHz, CDCl3) δ 7.51 (d, J = 2.0 Hz, 1H), 7.48 (dd, J = 3.6, 2.0 Hz, 2H), 7.45 (d, J = 2.0 Hz, 1H), 7.30 (t, J = 6.4 Hz, 2H), 7.26–7.20 (m, 7H), 4.01 (s, 2H), 2.38 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 141.20, 140.07, 139.11, 138.26, 136.96, 129.59, 129.42, 129.11, 128.65, 127.16, 126.98, 126.26, 41.73, 21.24.
4-(4-methoxybenzyl)-4′-methyl-1,1′-biphenyl (6b) [44]: Yellow oil (83.1 mg, 96%). 1H-NMR (400 MHz, CDCl3) δ 7.49 (s, 1H), 7.47 (d, J = 2.0 Hz, 2H), 7.45 (s, 1H), 7.23 (s, 2H), 7.21 (s, 2H), 7.14 (s, 1H), 7.12 (s, 1H), 6.85 (s, 1H), 6.83 (s, 1H), 3.95 (s, 2H), 3.77 (s, 3H), 2.37 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 158.14, 140.54, 139.02, 138.29, 136.93, 133.32, 130.03, 129.57, 129.28, 127.13, 126.97, 114.06, 55.41, 40.82, 21.23.
4-(4-fluorobenzyl)-4′-methyl-1,1′-biphenyl (6c): Yellow oil (73.7 mg, 89%).1H-NMR (400 MHz, CDCl3) δ 7.50 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.24–7.20 (m, 4H), 7.17 (dd, J = 8.8, 5.6 Hz, 2H), 6.98 (t, J = 8.8 Hz, 2H), 3.97 (s, 2H), 2.38 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 161.59 (d, J = 243.9 Hz), 139.86 (d, J = 1.4 Hz), 139.26, 138.16, 137.04, 136.85 (d, J = 3.3 Hz), 130.45 (d, J = 7.8 Hz), 129.60, 129.31, 127.22, 126.98, 115.40 (d, J = 21.2 Hz), 40.86, 21.24. HRMS (ESI) m/z calcd for C20H19FK+ (M + K)+ 315.09459, found 315.09357.
3-((4′-methyl-[1,1′-biphenyl]-4-yl)methyl)thiophene (6d): Colorless oil (45.2 mg, 57%). 1H-NMR (400 MHz, CDCl3) δ 7.50 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.0 Hz, 2H), 7.26 (t, J = 2.4 Hz, 2H), 7.23 (d, J = 8.0 Hz, 3H), 6.95 (dd, J = 4.8, 2.8 Hz, 2H), 4.01 (s, 2H), 2.38 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 139.53, 139.20, 136.99, 129.59, 129.24, 128.61, 127.17, 126.98, 125.81, 121.44, 36.30, 21.24. HRMS (ESI) m/z calcd for C18H17S+ (M + H)+ 265.10455, found 265.10495.
4-(bromomethyl)-4′-methyl-1,1′-biphenyl (7a) [45]: White solid (32.6 mg, 42%). 1H-NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 6.4Hz, 2H), 4.55 (s, 2H), 2.40 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 141.48, 137.69,137.56, 137.58, 129.70, 129.61, 127.48, 127.08, 33.63, 21.27.
4-methyl-4′-(4-methylbenzyl)-1,1′-biphenyl (7b) [46]: White solid, MP: 77–78 °C (20.4 mg, 25%). 1H-NMR (400 MHz, CDCl3) δ 7.51–7.44 (m, 4H), 7.23 (dd, J = 8.0 3.6 Hz, 4H), 7.11 (s, 4H), 3.97 (s, 2H), 2.38 (s, 3H), 2.32 (s, 3H). 13C-NMR (100 MHz, CDCl3) δ 140.38, 139.02, 138.31, 138.16, 136.92, 135.74, 129.57, 129.34, 128.97, 127.13, 126.98, 41.30, 21.23, 21.17.
4-methyl-1,1′-biphenyl (7c) [25]: White solid (46.8 mg, 92%). 1H-NMR (400 MHz, CDCl3) δ 7.57 (dd, J = 8.4, 1.6 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.41 (t, J = 7.6 Hz, 2H), 7.31 (t, J = 7.6 Hz, 1H), 7.24 (d, J = 8.0 Hz, 3H), 2.38 (s, 3H).

4. Conclusions

In conclusion, an efficient method for the selective Suzuki–Miyaura coupling of o-(or m-, or p-)chloromethyl bromobenzene with arylboronic acids was described. This Pd-catalyzed highly selective coupling reaction of the C(sp2)–Br bond was achieved by using PCy3·HBF4 as the ligand and Cs2CO3 as the base in a mixture of toluene/water (10:1). A series of chloromethyl-1,1′-biphenyl compounds were obtained in moderate-to-excellent yields. Importantly, the catalytic system exhibited a wide substrate scope and good functional group tolerance. Moreover, this protocol was extended to the one-pot dual arylation of 1-bromo-4-(chloromethyl)benzene, affording numerous unsymmetrical methylene-linked biaryl derivatives.

Supplementary Materials

Supplementary materials are available online. Figures S2–S46: 1H-, 13C-NMR, and HRMS of products.

Acknowledgments

We gratefully acknowledge financial support of this work by the National Natural Science Foundation of China (No. 21563025), the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT_15R46), and the Yangtze River scholar research project of Shihezi University (No. CJXZ201601).

Author Contributions

P.L. and X.-w.M. conceived and designed the experiments; M.-m.P. performed the experiments; B.D. and X.-m.L. contributed reagents/materials/analysis tools; Y.L. wrote the paper.

Conflicts of Interest

The authors declare no conflict of interest.

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  46. Zhang, Y.; Feng, M.T.; Lu, J.M. N-Heterocyclic carbene–palladium(II)–1-methylimidazole complex catalyzed Suzuki–Miyaura coupling of benzylic chlorides with arylboronic acids or potassium phenyltrifluoroborate in neat water. Org. Biomol. Chem. 2013, 11, 2266–2272. [Google Scholar] [CrossRef] [PubMed]
Sample Availability: Samples of the compounds are not available from the authors.
Molecules 23 00433 sch001 550
Scheme 1. Selective palladium-catalyzed Suzuki-Miyaura coupling reaction. (a) C(sp3)–C(sp2) coupling; (b) C(sp2)–C(sp2) coupling.
Scheme 1. Selective palladium-catalyzed Suzuki-Miyaura coupling reaction. (a) C(sp3)–C(sp2) coupling; (b) C(sp2)–C(sp2) coupling.
Molecules 23 00433 sch001
Molecules 23 00433 sch002 550
Scheme 2. Selective coupling reaction of 1-bromo-4-(bromo methyl)benzene with p-tolylboronic acid.
Scheme 2. Selective coupling reaction of 1-bromo-4-(bromo methyl)benzene with p-tolylboronic acid.
Molecules 23 00433 sch002
Molecules 23 00433 sch003 550
Scheme 3. Selective coupling reaction of bromobenzene or (chloromethyl)benzene with p-tolylboronic acid.
Scheme 3. Selective coupling reaction of bromobenzene or (chloromethyl)benzene with p-tolylboronic acid.
Molecules 23 00433 sch003
Table
Table 1. Optimized reaction conditions a.
Table 1. Optimized reaction conditions a.
Molecules 23 00433 i001
EntryPd(OAc)2PCy3∙HBF4Base/Equiv.T/°CYield/% b
12 mol %4 mol %NEt380(37) c
22 mol %4 mol %NaOH80(14) c
32 mol %4 mol %K3PO4∙3H2O80(69) c
42 mol %4 mol %K2CO380(84) c
52 mol %4 mol %Cs2CO38099(97) c
62 mol %PPh3/4 mol %Cs2CO3800
72 mol %4 mol %Cs2CO36074
81 mol %2 mol %Cs2CO38099
90.5 mol %1 mol %Cs2CO38099
100.2 mol %0.4 mol %Cs2CO38099
110.1 mol %0.2 mol %Cs2CO38023
a Reaction conditions: 1-bromo-4-(chloromethyl)benzene 0.30 mmol, p-tolylboronic acid 0.33 mmol, base 2 equiv., 1.0 mL toluene and 0.1 mL H2O, 2 h, Ar protection. b Gas chromatography-mass spectrometry (GC–MS) yield. c Isolated yield.
Table
Table 2. Selective coupling reaction of 1-bromo-4-(chloromethyl)benzene with arylboronic acid a.
Table 2. Selective coupling reaction of 1-bromo-4-(chloromethyl)benzene with arylboronic acid a.
Molecules 23 00433 i002
Molecules 23 00433 i003
3b, 79%		Molecules 23 00433 i004
3c, 87%		Molecules 23 00433 i005
3d, 83%
Molecules 23 00433 i006
3e, 93%		Molecules 23 00433 i007
3f, 83%		Molecules 23 00433 i008
3g, 75%
Molecules 23 00433 i009
3h, 98%		Molecules 23 00433 i010
3i, 73%		Molecules 23 00433 i011
3j, 90%
Molecules 23 00433 i012
3k, 47%		Molecules 23 00433 i013
3l, 50%		Molecules 23 00433 i014
3m, 73%
Molecules 23 00433 i015
3n, 77%		Molecules 23 00433 i016
3o, 86%		Molecules 23 00433 i017
3p, 57%
a Reaction conditions: 1-bromo-4-(chloromethyl)benzene 0.30 mmol, arylboronic acid 0.33 mmol, 0.2 mol % Pd(OAc)2, 0.4 mol % PCy3∙HBF4, 2 equiv. Cs2CO3, 1.0 mL toluene and 0.1 mL H2O, 80 °C, 2 h, Ar protection. The yields of isolated products are given.
Table
Table 3. Selective coupling reaction of arylboronic acid with 1-bromo-3-(chloromethyl)benzene a.
Table 3. Selective coupling reaction of arylboronic acid with 1-bromo-3-(chloromethyl)benzene a.
Molecules 23 00433 i018
Molecules 23 00433 i019
4a, 95%		Molecules 23 00433 i020
4b, 90%		Molecules 23 00433 i021
4c, 92%		Molecules 23 00433 i022
4d, 93%
Molecules 23 00433 i023
4e, 92%		Molecules 23 00433 i024
4f, 87%		Molecules 23 00433 i025
4g, 95%		Molecules 23 00433 i026
4h, 73%
a Reaction conditions: 1-bromo-3-(chloromethyl)benzene 0.30 mmol, arylboronic acid 0.33 mmol, 0.2 mol % Pd(OAc)2, 0.4 mol % PCy3∙HBF4, 2 equiv. Cs2CO3, 1.0 mL toluene and 0.1 mL H2O, 80 °C, 2 h, Ar protection. The yields of isolated products are given.
Table
Table 4. Selective coupling reaction of arylboronic acid with 1-bromo-2-(chloromethyl)benzene a.
Table 4. Selective coupling reaction of arylboronic acid with 1-bromo-2-(chloromethyl)benzene a.
Molecules 23 00433 i027
Molecules 23 00433 i028
5a, 97%		Molecules 23 00433 i029
5b, 95%		Molecules 23 00433 i030
5c, 89%		Molecules 23 00433 i031
5d, 92%
Molecules 23 00433 i032
5e, 88%		Molecules 23 00433 i033
5f, 87%		Molecules 23 00433 i034
5g, 95%		Molecules 23 00433 i035
5h, 80%
a Reaction conditions: 1-bromo-3-(chloromethyl)benzene 0.30 mmol, arylboronic acid 0.33 mmol, 0.2 mol % Pd(OAc)2, 0.4 mol % PCy3∙HBF4, 2 equiv. Cs2CO3, 1.0 mL toluene and 0.1 mL H2O, 80 °C, 2 h, Ar protection. The yields of isolated products are given.
Table
Table 5. One-pot dual arylations of 1-bromo-4-(chloromethyl)benzene a.
Table 5. One-pot dual arylations of 1-bromo-4-(chloromethyl)benzene a.
Molecules 23 00433 i036
Molecules 23 00433 i037
6a, 78%		Molecules 23 00433 i038
6b, 96%
Molecules 23 00433 i039
6c, 89%		Molecules 23 00433 i040
6d, 57%
a Reaction conditions: (1) 1-bromo-4-(chloromethyl)benzene 0.30 mmol, arylboronic acid 0.33 mmol, 2 mol % Pd(OAc)2, 0.4 mol % PCy3∙HBF4, 5 equiv. Cs2CO3, 1.0 mL toluene and 0.1 mL H2O, 80 °C, 2 h, Ar protection; (2) 4.0 mol % PPh3, arylboronic acid 0.33 mmol, 80 °C, 5 h, Ar protection. The yields of isolated products are given.

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Pei, M.-m.; Liu, P.; Liu, Y.; Lv, X.-m.; Ma, X.-w.; Dai, B. Pd-Catalyzed, Highly Selective C(sp2)-Br Bond Coupling Reactions of o-(or m-, or p-) Chloromethyl Bromobenzene with Arylboronic Acids. Molecules 2018, 23, 433. https://doi.org/10.3390/molecules23020433

AMA Style

Pei M-m, Liu P, Liu Y, Lv X-m, Ma X-w, Dai B. Pd-Catalyzed, Highly Selective C(sp2)-Br Bond Coupling Reactions of o-(or m-, or p-) Chloromethyl Bromobenzene with Arylboronic Acids. Molecules. 2018; 23(2):433. https://doi.org/10.3390/molecules23020433

Chicago/Turabian Style

Pei, Ming-ming, Ping Liu, Yan Liu, Xin-ming Lv, Xiao-wei Ma, and Bin Dai. 2018. "Pd-Catalyzed, Highly Selective C(sp2)-Br Bond Coupling Reactions of o-(or m-, or p-) Chloromethyl Bromobenzene with Arylboronic Acids" Molecules 23, no. 2: 433. https://doi.org/10.3390/molecules23020433

APA Style

Pei, M. -m., Liu, P., Liu, Y., Lv, X. -m., Ma, X. -w., & Dai, B. (2018). Pd-Catalyzed, Highly Selective C(sp2)-Br Bond Coupling Reactions of o-(or m-, or p-) Chloromethyl Bromobenzene with Arylboronic Acids. Molecules, 23(2), 433. https://doi.org/10.3390/molecules23020433

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