palladium-catalyzed suzuki cross-coupling of phenylhydrazine or (phenylsulfonyl)hydrazine

Job/Unit: O40126 /KAP1 Date: 14-04-14 16:23:56 Pages: 7

SHORT COMMUNICATION

DOI: 10.1002/ejoc.201400126

Palladium-Catalyzed Suzuki Cross-Coupling of Phenylhydrazine or(Phenylsulfonyl)hydrazine

Yahui Li,[a] Wei Liu,[a] Qingshan Tian,[a] Qing Yang,[b] and Chunxiang Kuang*[a]

Keywords: Synthetic methods / Cross-coupling / Palladium / Biaryls / Hydrazides

The palladium-catalyzed Suzuki cross-coupling of phenyl-hydrazine or (phenylsulfonyl)hydrazine was developed forthe preparation of biaryl compound in high yields. Moreover,

Introduction

Palladium-catalyzed cross-coupling reactions[1] throughselective cleavage of unreactive bonds, such as carbon–hydrogen,[2] carbon–carbon,[3] carbon–nitrogen,[4] and car-bon–sulfur bonds,[4] are valuable tools in modern organicsynthesis because they provide unique organic transforma-tions that are difficult to be performed using other meth-ods.[4] Among these reactions, the cross-coupling reactionthrough cleavage of the carbon–nitrogen[4] or carbon–sulfurbond[4] is rarely reported, especially for unreactive carbon–nitrogen and carbon–sulfur bonds. Generally, compoundscontaining carbon–nitrogen bonds may serve as candidatesfor the electrophilic counterparts in cross-coupling reac-tions; for example, diazonium salts,[4a–4c]ammonium salts,[5]

and aza heterocycles[6] have been utilized in several cross-coupling reactions. However, existing methods are stillplagued with problems such as limited substrate scope, un-stable nature of the substrates, and the need to use strongacids and an air-sensitive nickel catalyst.

Recently, Blakey and MacMillan developed a carbon–carbon bond-formation strategy through the nickel-cata-lyzed cleavage of unactivated carbon–nitrogen bonds byusing aryltrimethylammonium salts.[7] Inspired by thesepioneering studies, we speculated that phenylhydrazinemight also be utilized as an electrophile in cross-couplingreactions to form aryl–aryl bonds. Herein, we report thefirst Suzuki reaction of phenylhydrazine or (phenylsulfon-yl)hydrazine (Scheme 1) with various organoboron rea-

[a] Department of Chemistry, Tongji University,Siping Road 1239, Shanghai 200092, ChinaE-mail: [email protected]://chemweb.tongji.edu.cn/Teachers/Details/a1a31ffb-88aa-4733-8fa5-8db01611b440

[b] School of Life Sciences, Fudan University,Handan Road 220, Shanghai 200433,China

[c] Key Laboratory of Yangtze River Water Environment, Ministryof Education,Siping Road 1239, Shanghai 200092, ChinaSupporting information for this article is available on theWWW under http://dx.doi.org/10.1002/ejoc.201400126.

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these hydrazines were also used in other cross-coupling reac-tions, and a possible pathway of this reaction was examined.

gents. This new reaction may be used as a complement tothe classical Suzuki cross-coupling reaction.

Scheme 1. Pd-catalyzed cross-coupling of phenylhydrazine or(phenylsulfonyl)hydrazine with arylboronic acids.

Results and Discussion

Initially, phenylhydrazine (1a) and 4-methoxyphenyl-boronic acid (2a) were first chosen as the substrates for themodel reaction in the presence of Pd(OAc)2 (5 mol-%) andK2CO3 (2 equiv.) with toluene as the solvent in air. Thetarget cross-coupling product was obtained in 45% yield.However, the desired product was not observed if we usedortho-substituted phenylhydrazine or introduced electron-withdrawing groups on the aryl boronic acid. As such, vari-ous conditions were screened, and the results are summa-rized in Table 1. First, various catalysts, such as Pd-(PPh3)4, CuI, CuCl, Cu(OAc)2, CuO2, and CuBr2, werescreened (Table 1, entries 1–8). Pd(PPh3)4 (2 mol-%) pro-vided product 3a in the highest yield (86 %; Table 1, en-try 9). If the amount of the Pd catalyst was decreased to1 mol-%, coupling product 3a was obtained in 76 % yield(entry 13, Table 1). No reaction occurred in toluene if nocatalyst was used (Table 1, entry 5). It was found that thebase played a crucial role in this reaction. Na2CO3 pro-duced a higher yield of the product than K2CO3 and


Y. Li, W. Liu, Q. Tian, Q. Yang, C. KuangSHORT COMMUNICATIONCs2CO3 (Table 1, entries 2, 9, 10). The loading of the basealso played an important role in the reaction. The yield de-creased to 52% if the loading of the base was reduced from2 to 1 equiv. (Table 1, entry 12), and decreased to 30 % inthe absence of any base (Table 1, entry 11). Further investi-gation demonstrated that air was crucial for the reactionbecause a low yield of the product was observed in its ab-sence. After surveying a variety of catalysts, bases, and cata-lyst loadings, the combination of Pd(PPh3)4 (2 mol-%) andNa2CO3 (2 equiv.) in toluene at 40 °C for 2 h was deter-mined as the optimal conditions for this reaction. Further-more, this reaction proceeded smoothly at room tempera-ture, although higher efficiency was observed at 40 °C.Thus, this transformation is facile and practical, as it doesnot require the use of strong bases, an expensive catalyst,or the rigorous exclusion of air.

Table 1. Optimization of the reaction conditions.

[a] Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), catalyst(2 mol-%), and base (2 equiv.) in solvent (1 mL) in air at 40 °C for2 h in a sealed tube. [b] Yield of isolated product; n.r.: no reaction.[c] Na2CO3 (1 equiv.). [d] Pd(PPh3)4 (1 mol-%). [e] 2,2��-Bipyridine(5 mol-%). [f] 1,10-Phenanthroline (5 mol-%).

With the optimized reaction condition in hand, the gen-erality of this novel process was explored, and the resultsare summarized in Table 2. As already outlined, a widerange of phenylhydrazines incorporating electron-donatingand electron-withdrawing groups in the ortho, meta, andpara positions gave the desired products in good yields(Table 2, entries 6–11, 18, 19). Generally, electron-richphenylhydrazines were more reactive than electron-poorphenylhydrazines. An ortho-substituted phenylhydrazine

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also reacted readily to give the desired product in goodyield (Table 2, entries 8). The tolerance of ortho-substitutedarylyhydrazines is an advantage over diazonium salts, whichare sensitive to steric hindrance. To further illustrate theutility of this coupling reaction, different aryl boronic acidswere evaluated under the optimal reaction conditions. Awide range of aryl boronic acids incorporating electron-donating and electron-withdrawing groups in the ortho,meta, and para positions were also efficient in this Suzukireaction (Table 2, entries 1–6, 10, 14–17). For example, 1areacted with 2a to produce the coupling biaryl product in86% yield, whereas the reaction between 1a and 2d affordedthe product in 80% yield. Notably, many functional groupssuch as cyano and ester were compatible with this reaction(Table 2, entries 6, 17).

Table 2. Suzuki reaction of arylhydrazines with arylboronic acids.

[a] Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), Pd(PPh3)4

(2 mol-%), and Na2CO3 (2 equiv.) in toluene (1 mL) in air at 40 °Cfor 2 h. [b] Yield od isolated product.

Significant chemoselectivities were observed upon using(chlorophenyl)hydrazine and (bromoaryl)boronic acids inthis coupling reaction. For example, 1c reacted with 2a to


Preparation of Biaryls by Suzuki Cross-Coupling

form the desired product as the major product (Table 2, en-try 8), and 1e reacted with 2i to produce the desired productin 70 % yield (Table 2, entry 15). Relative to aryl bromides,arylhydrazines were more efficient electrophilic counter-parts under the reaction conditions. This feature is expectedto have many important applications in medicine and mate-rials chemistry.

We also explored whether this substrate could be ex-tended to some other cross-coupling reactions. As shownin Table 3, phenylhydrazine also worked well in couplingreactions with aryl halides to form cross-coupled productsin good yields; for example, 1a reacted with 4-iodophene-tole to form the cross-coupled product in 72 % yield. Uponemploying 1a in the Hiyama coupling reaction, the biphenylproduct was obtained in 62% yield (Scheme 2). The aboveresults indicate that phenylhydrazine should be an electro-philic coupling substrate at low temperatures and act as anucleophilic coupling partner at high temperatures underoptimized conditions.

Table 3. Cross-coupling of phenylhydrazines with aryl iodides.


(2 mol-%), and Na2CO3 (2 equiv.) in toluene (1 mL) in air at 80 °Cfor 4 h. [b] Yield of isolated product.

On the basis of the reaction of phenylhydrazine witharylboronic acids, we hypothesize that (phenylsulfonyl)-hydrazine could also react with arylboronic acids under thesame catalytic conditions. As shown in Table 4, the reactionof (4-methylphenylsulfonyl)hydrazide with (2-methoxy-phenyl)boronic acid resulted in high yields (71%).

Scheme 3. Proposed mechanism for the Suzuki cross-coupling of phenylhydrazine with arylboronic acids.

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Scheme 2. Hiyama reaction of phenylhydrazine with arylsilane.

Table 4. Cross-coupling of (phenylsulfonyl)hydrazine with aryl-boronic acids.


(2 mol-%), and Na2CO3 (2 equiv.) in toluene (1 mL) in air at 80 °Cfor 4 h. [b] Yield of isolated product.

A plausible reaction mechanism is outlined in Scheme 3;this mechanism is based on the literature[9] and the resultsof our experiments. First, arylhydrazine A is dehydrogen-ated in the presence of the base to produce diazene B.Oxidative addition of B to the Pd catalyst results in theformation of intermediate C. The existence of palladadiazir-idine complex C was established in previous work.[10] Theoxidative addition of palladium(0) to initially formed palla-dadiaziridine complex C cleaves the C–N bond to give two-palladium(II)-centered complex D, which promotes thetransmetalation of the arylboronic acid to form diarylpalla-dium species F and palladadiaziridine complex E, whichcollapses to give palladium(0), nitrogen gas, and water inthe presence of oxygen. Reductive elimination of F resultsin the formation of biaryl product G and regenerates thePd catalyst.


Y. Li, W. Liu, Q. Tian, Q. Yang, C. KuangSHORT COMMUNICATION

Conclusions

In conclusion, a new procedure for the preparation ofbiaryl compounds through the Pd-catalyzed Suzuki cross-coupling of arylhydrazines or (phenylsulfonyl)hydrazinewith various organoboron reagents was developed. Thisnovel method provides easy access to biaryl compounds byusing commercially available and inexpensive phenyl-hydrazine. The reaction did not require too much time,harsh reaction conditions, an expensive catalyst, or the ex-clusion of air. This cost-effective methodology will be veryattractive for both academia and industry because commer-cially available arylhydrazines are used as the coupling part-ners. This new reaction may be used in the future as a com-plement to the classical Suzuki cross-coupling reaction.

Experimental SectionGeneral: Unless stated otherwise, all reactions were performed un-der an air atmosphere. All solvents were used without further puri-fication. 1H NMR spectra were obtained at 400 MHz and recordedrelative to the tetramethylsilane signal (δ = 0 ppm) or residual pro-tiosolvent. 13C NMR spectra were obtained at 100 or 125 MHz,and chemical shifts were recorded relative to the solvent resonance(CDCl3, δ = 77.0 ppm). Data for 1H NMR are denoted as follows:chemical shift (δ, ppm), multiplicity [s = singlet, d = doublet, t =triplet, q = quartet, m = multiplet or unresolved, br. s = broadsinglet], coupling constant(s) (in Hz, integration). Data for 13CNMR are reported in terms of chemical shift (δ, ppm). Mass spec-tra (MS) were measured with an Agilent 6890/5973N.

General Procedure A: A mixture of phenylhydrazine (0.5 mmol,54 mg), 4-methoxyphenylboronic acid (1 mmol, 152 mg), Pd(PPh3)4 (2 mol-%), and Na2CO3 (1 mmol, 106 mg) in toluene (1 mL) wasstirred at 40 °C for 2 h in a sealed tube. The mixture was filteredand washed with CH2Cl2. The organic phase was filtered and con-centrated in vacuo. The resulting residue was purified by prepara-tive silica gel TLC to yield product 3.

General Procedure B: A mixture of phenylhydrazine (0.5 mmol,54 mg), 4-iodoanisole (1 mmol, 233 mg), Pd(PPh3)4 (2 mol-%), andNa2CO3 (1 mmol, 106 mg) in toluene (1 mL) was stirred at 80 °Cfor 4 h in a sealed tube. The mixture was filtered and washed withCH2Cl2. The organic phase was filtered and concentrated in vacuo.The resulting residue was purified by preparative silica gel TLC toyield product 3.

General Procedure C: A mixture of phenylhydrazine (0.5 mmol,54 mg), trimethoxyphenylsilane (1 mmol, 183 mg), Pd(PPh3)4

(2 mol-%), and KF(1 mmol, 52 mg) in 1,2-dichloroethane (1 mL)was stirred at 100 °C for 12 h in a sealed tube. The mixture wasfiltered and washed with CH2Cl2. The organic phase was filteredand concentrated in vacuo. The resulting residue was purified bypreparative silica gel TLC to yield product 3.

General Procedure D: A mixture of (phenylsulfonyl)hydrazide(0.5 mmol, 86 mg), 4-methoxyphenylboronic acid (1 mmol,152 mg), Pd(PPh3)4 (2 mol-%), and Na2CO3 (1 mmol, 106 mg) intoluene (1 mL) was stirred at 80 °C for 4 h in a sealed tube. Themixture was filtered and washed with CH2Cl2. The organic phasewas filtered and concentrated in vacuo. The resulting residue waspurified by preparative silica gel TLC to yield product 3.

4-Methoxybiphenyl:[1] According to general procedure A, the crudeproduct was purified by preparative silica gel TLC (n-hexane/ethyl


acetate = 10:1) to give 3a. White crystals, 86% yield. 1H NMR(400 MHz, CDCl3): δ = 7.54 (t, J = 8.2 Hz, 4 H), 7.42 (t, J =7.6 Hz, 2 H), 7.30 (t, J = 7.4 Hz, 1 H), 6.98 (d, J = 8.7 Hz, 2 H),3.85 (s, 3 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 159.24,140.90, 133.84, 128.80, 128.22, 126.80, 126.73, 114.29, 55.38 ppm.MS (EI): m/z = 184 [M+].

3-Methoxybiphenyl:[1] According to general procedure A, the crudeproduct was purified by preparative silica gel TLC (n-hexane/ethylacetate = 15:1) to give 3b. Pale yellow liquid, 88% yield. 1H NMR(400 MHz, CDCl3): δ = 7.59 (d, J = 7.2 Hz, 2 H), 7.44 (t, J =7.5 Hz, 2 H), 7.39–7.32 (m, 2 H), 7.18 (d, J = 7.8 Hz, 1 H), 7.13(d, J = 1.9 Hz, 1 H), 6.90 (dd, J = 8.2, 1.9 Hz, 1 H), 3.87 (s, 3 H)ppm. 13C NMR (101 MHz, CDCl3): δ = 160.10, 142.89, 141.23,129.90, 128.88, 127.55, 127.33, 119.80, 113.04, 112.81, 55.36 ppm.MS (EI): m/z = 184 [M+].

2-Methoxybiphenyl:[2] According to general procedure A, the crudeproduct was purified by preparative silica gel TLC (n-hexane/ethylacetate = 20:1) to give 3c. White power, 82% yield. 1H NMR(400 MHz, CDCl3): δ = 7.53 (d, J = 7.2 Hz, 2 H), 7.41 (t, J =7.5 Hz, 2 H), 7.33 (ddd, J = 6.8, 4.3, 2.4 Hz, 3 H), 7.08–6.95 (m, 2H), 3.82 (s, 3 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 156.53,138.61, 130.94, 130.80, 129.59, 128.65, 128.02, 126.95, 120.88,111.31, 55.59 ppm. MS (EI): m/z = 184 [M+].

3-Nitrobiphenyl:[3] According to general procedure A, the crudeproduct was purified by preparative silica gel TLC (n-hexane/ethylacetate = 10:1) to give 3d. Pale yellow solid, 80% yield. 1H NMR(400 MHz, CDCl3): δ = 8.46 (d, J = 1.8 Hz, 1 H), 8.21 (dd, J =8.2, 1.2 Hz, 1 H), 7.92 (d, J = 7.8 Hz, 1 H), 7.72–7.57 (m, 3 H),7.50 (t, J = 7.4 Hz, 2 H), 7.44 (t, J = 7.3 Hz, 1 H) ppm. 13C NMR(126 MHz, CDCl3): δ = 148.77, 142.91, 138.69, 133.04, 129.72,129.18, 128.56, 127.17, 122.04, 121.97 ppm. MS (EI): m/z = 199[M+].

2-Fluorbiphenyl:[4] According to general procedure A, the crudeproduct was purified by preparative silica gel TLC (n-hexane/ethylacetate = 20:1) to give 3e. Pale yellow solid, 72% yield. 1H NMR(400 MHz, CDCl3): δ = 7.56 (d, J = 8.0 Hz, 2 H), 7.48–7.41 (m, 3H), 7.37 (t, J = 7.3 Hz, 1 H), 7.31 (dd, J = 10.0, 4.6 Hz, 1 H), 7.24–7.12 (m, 2 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 159.8 (JCF

= 246 Hz, CF), 135.8 (C6H5), 130.8 (JCF = 3.6 Hz, CH), 129.2(C6H5), 129.0 (JCF = 3 Hz, CH), 128.9 (C6H5), 128.7 (C6H5), 128(C6H5), 127.4 (JCF = 36 Hz, C6H5F), 124.3 (JCF = 3.6 Hz, CH),116.1 (JCF = 22.5 Hz, CH) ppm. MS (EI): m/z = 172 [M+].

Methyl Biphenyl-3-carboxylate:[10] According to general pro-cedure A, the crude product was purified by preparative silica gelTLC (n-hexane/ethyl acetate = 10:1) to give 3f. Pale yellow solid,74% yield. 1H NMR (400 MHz, CDCl3): δ = 8.28 (s, 1 H), 8.02 (d,J = 7.7 Hz, 1 H), 7.79 (d, J = 7.8 Hz, 1 H), 7.63 (d, J = 7.3 Hz, 2H), 7.31–7.45 (m, 4 H), 3.95 (s, 3 H) ppm. 13C NMR (126 MHz,CDCl3): δ = 167.02, 145.66, 140.03, 130.12, 128.94, 128.16, 127.29,127.06, 52.13 ppm. MS (EI): m/z = 212 [M+].

3-Nitro-4�-methylbiphenyl:[4] According to general procedure A, thecrude product was purified by preparative silica gel TLC (n-hexane/ethyl acetate = 10:1) to give 3g. Pale yellow solid, 83% yield. 1HNMR (400 MHz, CDCl3): δ = 8.47 (s, 1 H), 8.20 (dd, J = 8.2,1.3 Hz, 1 H), 7.92 (d, J = 8.1 Hz, 1 H), 7.62 (t, J = 8.0 Hz, 1 H),7.56 (d, J = 8.1 Hz, 2 H), 7.33 (d, J = 7.9 Hz, 2 H), 2.46 (s, 3 H)ppm. 13C NMR (126 MHz, CDCl3): δ = 148.77, 142.84, 138.58,135.79, 132.81, 129.88, 129.64, 126.99, 121.73, 21.16 ppm. MS (EI):m/z = 213 [M+].

2,4-Dichloro-4�-methylbiphenyl:[5] According to general pro-cedure A, the crude product was purified by preparative silica gel



TLC (n-hexane/ethyl acetate = 10:1) to give 3h. Pale yellow liquid,72% yield. 1H NMR (400 MHz, [D6]DMSO): δ = 7.53 (d, J =2.0 Hz, 1 H), 7.31 (dd, J = 8.3, 2.1 Hz, 1 H), 7.23 (d, J = 8.3 Hz,1 H), 7.19 (d, J = 8.7 Hz, 2 H), 6.85 (d, J = 8.7 Hz, 2 H), 3.63 (s, 3H) ppm. 13C NMR (126 MHz, CDCl3): δ = 159.35, 138.74, 133.32,133.27, 132.09, 130.67, 130.55, 129.69, 127.13, 113.62, 55.32 ppm.MS (EI): m/z = 252 [M+].

2-(4-Methoxyphenyl)naphthalene:[6] According to general pro-cedure A, the crude product was purified by preparative silica gelTLC (n-hexane/ethyl acetate = 20:1) to give 3i. White solid, 88%yield. 1H NMR (400 MHz, CDCl3): δ = 7.91 (t, J = 8.9 Hz, 2 H),7.84 (d, J = 8.1 Hz, 1 H), 7.57–7.38 (m, 6 H), 7.04 (d, J = 8.5 Hz,2 H), 3.90 (s, 3 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 159.06,140.02, 133.97, 133.23, 131.95, 131.21, 128.37, 127.44, 127.02,126.17, 126.03, 125.80, 125.51, 113.83, 55.41 ppm. MS (EI): m/z =234 [M+].

4-Fluoro-2�-methoxybiphenyl:[4] According to general procedure A,the crude product was purified by preparative silica gel TLC (n-hexane/ethyl acetate = 20:1) to give 3j. Pale yellow solid, 81 % yield.1H NMR (400 MHz, CDCl3): δ = 7.53–7.44 (m, 4 H), 7.10 (t, J =8.7 Hz, 2 H), 6.97 (d, J = 8.7 Hz, 2 H), 3.85 (s, 3 H) ppm. 13CNMR (126 MHz, CDCl3): δ = 162 (d, JCF = 245.1 Hz), 159.13,136.98, 132.87, 128.1 (d, JCF = 7.4 Hz), 128.04, 115.61, 115.44,114.27, 55.37 ppm. MS (EI): m/z = 202 [M+].

3-Nitro-4�-methoxybiphenyl:[4] According to general procedure A,the crude product was purified by preparative silica gel TLC (n-hexane/ethyl acetate = 20:1) to give 3k. Pale yellow solid, 80%yield. 1H NMR (400 MHz, CDCl3): δ = 8.41 (s, 1 H), 8.15 (d, J =8.2 Hz, 1 H), 7.87 (d, J = 7.1 Hz, 1 H), 7.59–7.55 (m, 3 H), 7.02(d, J = 7.7 Hz, 2 H), 3.87 (s, 3 H) ppm. 13C NMR (126 MHz,CDCl3): δ = 160.10, 148.79, 142.50, 132.51, 131.11, 129.63, 128.28,121.41, 121.38, 114.61, 55.42 ppm. MS (EI): m/z = 229 [M+].

4-Fluoro-2�-methoxybiphenyl:[4] According to general procedure A,the crude product was purified by preparative silica gel TLC (n-hexane/ethyl acetate = 20:1) to give 3l. Pale yellow solid, 83% yield.1H NMR (400 MHz, CDCl3): δ = 7.48 (tt, J = 14.7, 5.1 Hz, 4 H),7.14–7.06 (m, 2 H), 7.00–6.94 (m, 2 H), 3.85 (s, 3 H) ppm. 13CNMR (126 MHz, CDCl3): δ = 162 (d, JCF = 245.1 Hz), 159.13,136.98, 132.87, 128.1 (d, JCF = 7.4 Hz), 128.04, 115.61, 115.44,114.27, 55.37 ppm. MS (EI): m/z = 202 [M+].

2-Fluoro-4�-methoxybiphenyl:[7] According to general procedure A,the crude product was purified by preparative silica gel TLC (n-hexane/ethyl acetate = 20:1) to give 3m. Yellow solid, 76% yield.1H NMR (400 MHz, CDCl3): δ = 7.50 (d, J = 7.3 Hz, 2 H), 7.41(td, J = 7.8, 1.5 Hz, 1 H), 7.29 (dd, J = 10.8, 4.9 Hz, 1 H), 7.18(ddd, J = 23.6, 13.9, 5.6 Hz, 2 H), 6.99 (d, J = 8.8 Hz, 2 H), 3.86(s, 3 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 159.8 (d, J =247 Hz), 159.2, 130.57, 130.53, 130.2, 130.1, 128.5, 128.4, 128.2,124.3 (d, J = 3.7 Hz), 116.1 (d, J = 23.1 Hz), 113.9, 55.3 ppm. MS(EI): m/z = 202 [M+].

2-Bromo-4�-methoxybiphenyl:[8] According to general procedure A,the crude product was purified by preparative silica gel TLC (n-hexane/ethyl acetate = 10:1) to give 3n. Pale yellow liquid, 70%yield. 1H NMR (400 MHz, CDCl3): δ = 7.66 (d, J = 8.1 Hz, 1 H),7.39–7.29 (m, 4 H), 7.21–7.12 (m, 1 H), 7.01–6.93 (m, 2 H), 3.86(s, 3 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 159.17, 142.28,133.61, 133.18, 131.44, 130.63, 128.49, 127.45, 122.98, 113.46,55.32 ppm. MS (EI): m/z = 262 [M+].

4-Methoxybiphenyl-4�-carbonitrile:[11] According to general pro-cedure A, the crude product was purified by preparative silica gelTLC (n-hexane/ethyl acetate = 10:1) to give 3o. Pale yellow liquid,


70% yield. 1H NMR (400 MHz, CDCl3): δ = 7.70 (d, J = 8.3 Hz,2 H), 7.64 (d, J = 8.3 Hz, 2 H), 7.54 (d, J = 8.7 Hz, 2 H), 7.01 (d,J = 8.7 Hz, 2 H), 3.87 (s, 3 H) ppm. 13C NMR (126 MHz, CDCl3):δ = 160.26, 145.22, 132.58, 131.49, 128.37, 127.11, 119.11, 114.59,110.11, 55.42 ppm. MS (EI): m/z = 209 [M+].

4-Methoxy-2�-methoxybiphenyl:[11] According to general pro-cedure A, the crude product was purified by preparative silica gelTLC (n-hexane/ethyl acetate = 10:1) to give 3p. Pale yellow liquid,82% yield. 1H NMR (400 MHz, CDCl3): δ = 7.49 (d, J = 8.7 Hz,2 H), 7.30 (dd, J = 11.8, 4.5 Hz, 2 H), 7.07–6.92 (m, 4 H), 3.84 (s, 3H) ppm. 13C NMR (126 MHz, CDCl3): δ = 158.74, 156.54, 130.99,130.75, 130.67, 130.43, 128.24, 120.91, 113.57, 111.30, 55.59,55.31 ppm. MS (EI): m/z = 214 [M+].

4-Ethoxybiphenyl:[9] According to general procedure B, the crudeproduct was purified by preparative silica gel TLC (n-hexane/ethylacetate = 10:1) to give 3q. White crystal, 72% yield. 1H NMR(400 MHz, CDCl3): δ = 7.54 (dd, J = 13.4, 8.1 Hz, 4 H), 7.41 (t, J

= 7.6 Hz, 2 H), 7.30 (t, J = 7.4 Hz, 1 H), 6.97 (d, J = 8.6 Hz, 2 H),4.08 (q, J = 7.0 Hz, 2 H), 1.44 (t, J = 7.0 Hz, 3 H) ppm. 13C NMR(126 MHz, CDCl3): δ = 158.57, 140.92, 133.65, 128.74, 128.15,126.74, 126.64, 114.81, 63.55, 14.91 ppm. MS (EI): m/z = 198 [M+].

Biphenyl:[1] According to general procedure C, the crude productwas purified by preparative silica gel TLC (n-hexane) to give 3r.White crystals, 62% yield. 1H NMR (400 MHz, CDCl3): δ = 7.63–7.57 (m, 4 H), 7.45 (t, J = 7.6 Hz, 4 H), 7.35 (t, J = 7.3 Hz, 2 H)ppm. 13C NMR (126 MHz, CDCl3): δ = 141.28, 128.78, 127.28,127.20 ppm. MS (EI): m/z = 154 [M+].

2-Methoxy-4�-methylbiphenyl:[10] According to general pro-cedure C, the crude product was purified by preparative silica gelTLC (n-hexane/ethyl acetate = 20:1) to give 3s. Yellow solid, 71%yield. 1H NMR (400 MHz, CDCl3): δ = 7.43 (d, J = 8.0 Hz, 2 H),7.31 (td, J = 6.0, 3.0 Hz, 2 H), 7.22 (d, J = 7.8 Hz, 2 H), 7.05–6.95(m, 2 H), 3.81 (s, 3 H), 2.66 (s, 3 H) ppm. 13C NMR (101 MHz,CDCl3): δ = 156.54, 136.63, 135.63, 130.83, 130.74, 129.44, 128.78,128.41, 120.83, 111.21, 55.56, 21.26 ppm. MS (EI): m/z = 198 [M+].

Supporting Information (see footnote on the first page of this arti-cle): Copies of the 1H and 13C NMR spectra.

Acknowledgments

The authors thank the National Natural Science Foundation ofChina (NSFC) (grant number 21272174), the Key Projects ofShanghai in Biomedicine (grant number 08431902700), and theScientific Research Foundation of the State Education Ministry forReturned Overseas Chinese Scholars for support of this research.

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Received: January 24, 2014Published Online: �



Cross-Coupling

Y. Li, W. Liu, Q. Tian, Q. Yang,C. Kuang* ......................................... 1–7

Palladium-Catalyzed Suzuki Cross-Cou-pling of Phenylhydrazine or (Phenylsulf-onyl)hydrazine

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palladium-catalyzed suzuki cross-coupling of phenylhydrazine or (phenylsulfonyl)hydrazine

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