General and highly efficient fluorinated-N-heterocyclic carbene–based catalysts for the palladium-catalyzed Suzuki–Miyaura reaction

Tetrahedron 68 (2012) 6535e6547

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General and highly efficient fluorinated-N-heterocyclic carbeneebased catalysts for the palladium-catalyzed SuzukieMiyaura reaction Taoping Liu, Xiaoming Zhao, Qilong Shen, Long Lu * Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, PR China

a r t i c l e i n f o

a b s t r a c t

Article history: Received 13 March 2012 Received in revised form 14 May 2012 Accepted 18 May 2012 Available online 26 May 2012

A general and highly efficient trifluoromethylated-N-heterocyclic carbene (NHC)-based catalyst for the palladium-catalyzed SuzukieMiyaura reaction was reported. In the presence of the catalyst, reactions of non-activated aryl chlorides and triflates with aryl boronic acids occurred at room temperature with good to excellent yields (63e98%). In addition, catalysts generated from a combination of Pd(OAc)2/ imidazolium salt 6a is not only effective for the coupling of heteroaryl boronic acid with aryl halides and heteroaryl halides, but also efficient for coupling of other heteroaryl halides and heteroaryl boronic acids. Finally, the catalyst is highly effective for SuzukieMiyaura reaction of aryl bromides and chlorides with 0.01e0.1 mol % loading if the temperature was raised at refluxed THF/H2O. Ó 2012 Elsevier Ltd. All rights reserved.

Keywords: SuzukieMiyaura reaction Fluoride N-Heterocyclic carbene Aryl halides Heteroaryl halides

1. Introduction The SuzukieMiyaura reaction, coupling of an aryl halide with an organoboron reagent, has become arguably one of the most efficient methods for the construction of carbonecarbon bond in organic synthesis both in a laboratory and industrial scale.1 Early works in the SuzukieMiyaura reaction were conducted using triarylphosphines as the ancillary ligand. In the last 10 years, extensive efforts from the groups of Buchwald,2 Fu,3 Herrmann,4 Nolan,5 Beller,6 and others7,8 have led to the discovery of much more efficient catalysts by employing electron-rich, sterically bulky dialkylbiarylphines, trialkyl-phosphines, or N-heterocyclic carbenes. The enhanced reactivity of the catalysts has dramatically expanded the scope of the SuzukieMiyaura reaction to include unactivated aryl chlorides, aryl tosylates, heteroaryl halides or boronic acids, and hindered substrates. Among these catalysts, highly reactive palladium complexes containing N-heterocyclic carbenes (NHCs)9 are especially attractive because they are: (1) sterically demanding ligands with better s-donor ability than tertiary phosphines; (2) low toxicity; (3) high dissociation energies of the PdeNHC bond; and (4) convenient preparation. Herrmann initially reported Pd(NHC)2 (NHC¼1,3-bisadamantlyimidazolin-2-ylidene) catalyzed the coupling of aryl chlorides with arylboronic acids at room temperature.4 More recently, Nolan and Organ disclosed independently that monocarbene-

* Corresponding author. E-mail address: [email protected] (L. Lu). 0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2012.05.068

palladium complex (carbene)Pd(cinnamyl)Cl or (carbene)Pd(3bromopyridine)Cl2 displays much higher reactivity in the SuzukieMiyaura cross-coupling of aryl chlorides with low catalyst loading.5,8 We recently initiated a project to study if fluoroalkylated NHCs will enhance the catalytic activity of the catalyst since it is well known that the fluoroalkyl group is electron withdrawing and can adjust the electronic effect of the ligand. Herein, we report that catalysts generated from a combination of Pd(OAc)2 and fluorinated NHCs are much more reactive for the SuzukieMiyaura reaction than those catalysts from non-fluorinated counterparts. The scope of the reaction was studied to include room temperature coupling of unactivated aryl chlorides, coupling of heteroaryl halides or heteroaryl boronic acids, and coupling of aryl bromides and chlorides with low catalyst loadings. 2. Results and discussion 2.1. Preparation of trifluoromethylated NHCs Trifluoromethylated NHCs9 were prepared from readily available 2,4,6-tribromoaniline acetate in six steps, as illustrated in Scheme 1. Treatment of 2,4,6-tribromoaniline acetate 1 with 3,3,3-trifluoro-1-propene under the Heck conditions, followed by hydrogenation and deprotection under acidic conditions gave 2,4,6-tri(trifluoromethylpropanyl)-aniline 4 in 57% yield over three steps. Condensation of compound 4 with glyoxal, subsequent reduction by NaBH4, and cyclization with HC(OEt)3 afforded the desired imidazolium salt 6a in 62% yield of three steps (Scheme 1).

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T. Liu et al. / Tetrahedron 68 (2012) 6535e6547

Br

NHCOCH3 Br CF3

+ Br

NHCOCH3

15 mol% Pd(OAc)2 5.0 equiv. NaOAc 3.0 equiv. Bu4NBr

F3C

CF3

DMF, 90 oC, 24 h 78% CF3 3

1 NH2 i) H2 (1atm), Pd/C, EtOAc, RT ii) Me3OBF4, CH2Cl2, RT iii) CF3COOH, MeOH, RT

F3C

CF3

57%

H

H

O

O

MeOH, HCO2H, RT, 24 h 86% CF3 4

R R

R N

R

N

R

i) NaBH4, THF/MeOH, 95% ii) HC(OEt)3, NH4Cl, 76% R R

R N

R

R

N Cl

R R

R = CH2CH2CF3, 6a

R = CH2CH2CF3, 5 Scheme 1. Preparation of imidazolium salt 6a.

Initially, the SuzukieMiyaura reaction of p-chloroanisole and phenylboronic acid was investigated in the presence of in situ generated palladium catalysts from 3 mol % of Pd(OAc)2 and 6 mol % of 6a with different bases in different solvents at room temperature. Less than 5% of the coupled product was observed when the reaction was conducted in THF using K2CO3 or K3PO4 as the base (Table 1, entries 1 and 2). We reasoned that the low solubility of the base in THF is likely the cause of low conversion. When the reaction was conducted in THF/H2O (5:1, v/v) mixed solvent with K2CO3 as the base, the yield of the product was significantly improved to 62% (Table 1, entry 3). Switching the base to K3PO4 led to even higher yield (91%, Table 1, entry 5). The amount of water influences the reaction slightly. Reactions in the presence of different amount of added water occurred to high yields if the ratio of THF/H2O is higher than 2:1 (Table 1, entries 9e11). Effects of palladium precursors were further studied and it was found that using other palladium precursors such as Pd(PPh3)4, Pd2(dba)3, or PdCl2 resulted in much lower yields or no product (Table 1, entries 6e8). In contrast with Nolan’s conclusion that the ligand/palladium ratio close to 1 generally enhances the catalytic activity,5a the reaction catalyzed by Pd(OAc)2/6a was insensitive to the ligand precursor/ palladium ratio when the catalyst loading is higher than 0.5 mol %. Reactions in the presence of both 1:1 or 2:1 ratio of ligand precursor/palladium occurred to full conversion and gave the desired products in 90% and 91% yields, respectively (Table 1, entries 5 and 12). However, when the catalyst loading was lowered to 0.1 mol %, reactions in the presence of catalyst with 2:1 ratio of ligand precursor 6a/palladium occurred to 56% yield, while the same reaction in the presence of catalyst with 1:1 ratio of ligand 6a/palladium gave the desired product in 16% yield.

2.2. Study of the activity of palladium complexes generated from trifluorinated imidazolim salt 6a and non-perfluorinated imidazolium salts 6be6e and 7ae7c in the SuzukieMiyaura reaction To probe the fluorine-effect of imidazolium salt 6a that gave rise to high reactivity, we prepared a number of non-fluorinated analogs

Table 1 Effect of different catalysts, solvents, and bases on the SuzukieMiyaura reaction of pchloroanisole with phenylboronic acid at room temperaturea

Cl + MeO

PhB(OH)2

Catalyst Base Solvent, RT

Ph MeO

Entry

Catalyst/ligand

Base

Solvent

Yieldb (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(PPh3)4 PdCl2 Pd2(dba)3 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2

K2CO3 K3PO4 K2CO3 Na2CO3 K3PO4 K3PO4 K3PO4 K3PO4 K3PO4 K3PO4 K3PO4 K3PO4 K3PO4 K3PO4

THF THF THF/H2O THF/H2O THF/H2O THF/H2O THF/H2O THF/H2O THF/H2O THF/H2O THF/H2O THF/H2O THF/H2O THF/H2O

<5 <5 62 21 91 <5 d d 92 95 78 90c 16d 56e

(5:1) (5:1) (5:1) (5:1) (5:1) (5:1) (10:1) (2:1) (1:5) (5:1) (5:1) (5:1)

a Standard conditions: Pd(OAc)2 (3 mol %), 6a (6 mol %), p-chloroanisole (0.8 mmol), phenyl boronic acid (1.2 mmol), K3PO4 (2.8 mmol), THF/H2O (5:1), room temperature, 3 h. b Isolated yield. c Pd(OAc)2 (0.5 mol %) and 6a (1.0 mol %) were used, room temperature, 12 h. d Pd(OAc)2 (0.1 mol %) and 6a (0.1 mol %) were used. e Pd(OAc)2 (0.1 mol %) and 6a (0.2 mol %) were used.

6bee and 8aec of imidazolium salt 6a and evaluated the catalytic reactivity of complexes containing non-fluorinated NHCs derived from 6bee and 8aec. Imidazolium salts 6bee with saturated backbone and 8aed with unsaturated backbone were prepared according to the procedure reported in the literature. A comparison of the performance of the catalysts generated from these imidazolium salts in the SuzukieMiyaura reaction of p-chloroanisole and phenylboronic acid at room temperature is shown in Table 2. Interestingly, catalysts generated from non-fluorinated imidazolium salts 6bee gave the coupling product in much lower yields after 3 h at room temperature. For example, imidazolium salt 6d

T. Liu et al. / Tetrahedron 68 (2012) 6535e6547 Table 2 SuzukieMiyaura reaction in the presence of the catalyst generated from different imidazolium saltsa

Cl + PhB(OH)2 MeO R R

R N

R

Ph

K3PO4 THF/H2O (5:1) MeO RT R RR

N Cl

Pd(OAc)2/NHC

R

N R

R = CH2CH2CH3, 6b CH2CH2CH2CH3, 6c CH2CH2CH(CH3)2, 6d CH3, 6e

R

N Cl

R

6537

give the desired products after 12 h at room temperature in excellent yield (Table 3, entries 1e6). Reactions of sterically hindered aryl chlorides at mild conditions are challenging. With the catalyst generated from trifluoromethylated imidazolium salt 6a, 2-chloroanisole and 2-chlorotoluene coupled with arylboronic acids in excellent yields (Table 3, entries 7e9). Even hindered 2,6dimethylphenyl chloride gave the coupled product in good to excellent yields (Table 3, entries 11 and 12). Electron-poor arylchloride such as 4-acetylphenyl chloride also was equally effective in the presence of catalyst generated from trifluoromethylated imidazolium salt 6a and excellent yields were obtained when coupled with arylboronic acid (Table 3, entry 13).

R

R = CH2CH2CH3, 8a CH2CH2CH2CH3, 8b CH3, 8c

Entry

Catalyst

Conversionb (%)

1 2 3 4 5 6 7 8

Pd(OAc)2/6a Pd(OAc)2/6b Pd(OAc)2/6c Pd(OAc)2/6d Pd(OAc)2/6e Pd(OAc)2/8a Pd(OAc)2/8b Pd(OAc)2/8c

100c (91) 28 38 56 18 39 51 28

a

Standard condition: Pd(OAc)2 (3 mol %), 6a (6 mol %), p-chloroanisole (0.8 mmol), phenyl boronic acid (1.2 mmol), K3PO4 (2.8 mmol), THF/H2O (5:1), room temperature, 3 h. b Determined by GC. c Isolated yield.

with an iso-pentyl group, which is sterically similar to a 3,3,3-trifluoro-propyl group formed much less reactive catalysts than did imidazolium salt 6a (Table 2, entry 4). Imidazolium salts 6be6c and 6e with smaller steric hindrance formed much lesser active catalyst than did imidazolium salt 6a. The catalysts from these imidazolium salts formed the coupled product in 18e38% yields (Table 2, entries 2, 3, and 5). Likewise, catalysts generated from imidazolium salts 8aec with unsaturated backbone were much less reactive than those from imidazolium salt 6a. Reactions of 4-chloroanisole with phenylboronic acid in the presence of 3 mol % these catalysts gave the desired products in 28e51% yields. From these studies, we conclude that the steric hindrance of the trifluoromethyl group in the imidazolium salt 6a does not contribute significantly to the high reactivity of the catalyst but is very important for reactivity of the catalyst. We attribute the high reactivity of the catalyst from imidazolium salt 6a to the strong electron withdrawing trifluoromethyl group that (1) decreases the electron density of the corresponding carbene, which facilitate the dissociation of NHC from Pd(NHC)2 to generate active monocarbenepalladium species; (2) makes the monocarbene-palladium species less electron-rich, which promotes the reductive-elimination in the catalytic cycle to form the product. 2.3. Scope of the SuzukieMiyaura reaction of electron-rich aryl chlorides at room temperature Under the optimized reaction conditions as shown in Table 1, entry 12, we next explored the scope of the SuzukieMiyaura reaction of a variety of aryl chlorides with arylboronic acids, and the results were summarized in Table 2. Reactions of electron-rich aryl chlorides such as 4-methoxyphenylchloride and 4-chlorotoluene with a number of arylboronic acids occurred to full conversion to

2.4. SuzukieMiyaura reaction of aryl triflates at room temperature Aryl triflates are very useful coupling partners in the crosscoupling reaction and considered as attractive alternatives to aryl halides since they can be easily prepared from readily available phenols. The catalyst generated from trifluoromethylated imidazolium salt 6a was effective for the coupling of aryl triflates at room temperature. Reactions of o, m, p-tolyl triflates occurred to give the desired products in good to excellent yields (Table 4, entries 1e5). 2.5. SuzukieMiyaura reaction of heteroaryl halides or heteroaryl boronic acids Hetero-biaryls are important structure motifs in many biologically active molecules, pharmaceuticals, and therapeutic drugs.10 In recent years, tremendous efforts have been focused on the discovery of active catalyst for coupling of heteroaryl halides or heteroaryl boronic acids including substrates containing nitrogen heterocycles.11 The presence of such groups often causes the deactivation of the catalysts and requires high catalyst loading. For example, thiophenes are found in numerous natural products as well as molecules for highly conducting oligomers and polymers. However, the SuzukieMiyaura reaction of thiophene boronic acid was problematic. It was found that catalysts generated from imidazolium salt 6a were highly effective for SuzukieMiyaura reaction of 3-thiophene boronic acid. 3-Thiophene boronic acid coupled with a variety of aryl chlorides to give the desired coupled products in 85e95% yields (Table 5, entries 1e5). More interesting, reactions of 3-thiophene boronic acid with unactivated heteroaryl chlorides such as 3-chloropyridine and 5-methyl-2-chlorothiophene occurred to full conversion after 12 h at reflux to give the desired coupled products in 87% and 90% yield, respectively (Table 5, entries 6 and 7). Catalysts generated from imidazolium salt 6a are not only effective for the coupling of 3-thiophene boronic acid with aryl halides and heteroaryl halides, but also efficient for coupling of other heteroaryl halides and heteroaryl boronic acids. Unactivated heteroaryl halides are challenging substrates in SuzukieMiyaura reactions. However, by using 3 mol % Pd(OAc)2/6 mol % imidazolium salt 6a, reactions of a variety of unactivated aryl or heteroaryl chlorides proceeded smoothly in good to excellent yields (Table 5, entries 12e17). Other heteroaryl boronic acids such as 3-pyridyl boronic acid or 2-benzofuryl boronic acid also coupled with unactivated aryl or heteroaryl chlorides under the Pd(OAc)2/imidazolium salt 6a in excellent yields (Table 5, entries 8e10). 2.6. SuzukieMiyaura reaction of aryl halides with low catalyst loading Lowering the loading of the homogeneous catalyst is highly desirable due to not only the decreased cost of the catalyst and more importantly the ease for its removal, particularly on industrial

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T. Liu et al. / Tetrahedron 68 (2012) 6535e6547

Table 3 Room-temperature SuzukieMiyaura coupling of aryl chlorides with arylboronic acidsa Entry

Aryl chloride

Arylboronic acid

1

MeO

Cl

2

MeO

Cl

MeO

Cl

MeO

Cl

5

MeO

Cl

6

Me

B(OH)2

Yieldc (%)

Product

MeO

Me B(OH)2

9b

97b

9c

95b

9d

95b

9e

91b

9f

89

9g

98

9h

87

MeO CF3

B(OH)2

MeO MeO

OMe 4

91

Me

F3C 3

9a

B(OH)2

t-Bu

B(OH)2

B(OH)2

Cl

MeO

MeO

Bu-t

Me

OMe

OMe

7

B(OH)2

Cl OMe

Me

Me

8

Cl

B(OH)2 MeO

Me

Me

OMe

9

Cl

9i

87b,d

9j

96

9k

84b

9l

63b

B(OH)2 MeO

MeO

MeO

Cl

10

B(OH)2

Me

Me Cl

11

MeO

OMe

B(OH)2

Me

Me

Me Cl

12

Me OMe

OMe B(OH)2

Me 13

a b c d

Me

O Cl

B(OH)2

O

9m

98

Standard condition: Pd(OAc)2 (0.5 mol %), 6a (1.0 mol %), aryl chloride (0.8 mmol), aryl boronic acid (1.2 mmol), K3PO4 (2.8 mmol), THF/H2O (5:1), room temperature, 12 h. Pd(OAc)2 (3 mol %) and 6a (6 mol %)were used. Isolated yield. Along with 3e5% of biphenyl, respectively.

T. Liu et al. / Tetrahedron 68 (2012) 6535e6547

6539

Table 4 Room-temperature SuzukieMiyaura coupling of aryl triflates with arylboronic acidsa Entry

Aryl triflate

Arylboronic acid

Me

Me

1

B(OH)2

OTf Me

9n

96

9o

92

9p

92

9q

83

9r

95

Me

2

B(OH)2

OTf

3

Yieldb (%)

Product

Me

OTf

B(OH)2

Me

Me

Me

4

OTf

Me

MeO

B(OH)2

OMe

Me

OMe

5

OTf

B(OH)2 MeO

a Standard condition: Pd(OAc)2 (0.5 mol %), 6a (1.0 mol %), aryl chloride (0.8 mmol), aryl boronic acid (1.2 mmol), K3PO4 (2.8 mmol) 10a, THF/H2O (5:1), room temperature, 12 h. b Isolated yield.

scale for questions of toxicity of the impurity in the final product.12 It was found that catalysts generated from imidazolium salt 6a is highly effective for SuzukieMiyaura reaction with 0.01e0.1 mol % loading if the temperature was raised at refluxed THF/H2O (5:1), as shown in Table 6. For example, reactions of hindered 2bromoanisole with electronic neutral or rich aryl boronic acids occurred with 0.01 mol % Pd(OAc)2 to give the desired products in good to excellent yields (75e95%) (Table 6, entries 1e4). Reactions with electron-poor aryl boronic acids required 0.1 mol % catalyst to full conversion (Table 6, entries 5 and 6). Reactions of activated aryl chlorides and bromides with aryl boronic acids occurred with 0.01e0.05 mol % loading to afford the desired products in good to excellent yields (Table 6, entries 8e12). Nolan has shown that monocarbene-palladium complex (carbene) Pd(cinnamyl)Cl displays much higher reactivity than Pd(NHC)2 in the SuzukieMiyaura cross-coupling.5a However, in our cases, the high reactive catalyst required 2 equiv of trifluoromethylated NHC for one palladium to give high efficiency. When the ratio of NHC/Pd dropped to 1, reaction of p-chloroanisole with phenyl boronic acid occurred with 17% yield in the presence of 0.1 mol % catalyst. 3. Conclusions In summary, we have demonstrated that catalyst generated from trifluoromethylated imidazolium salt 6a is a highly reactive and practical catalyst for SuzukieMiyaura coupling of aryl and heteroaryl chlorides, bromides and triflates. Reactions of nonactivated aryl chlorides and triflates occurred smoothly in good to excellent yields in the presence of 0.5 mol % Pd(OAc)2 and 1.0 mol % 6a. Reactions of heteroaryl halides or heteroaryl boronic acids however, required higher catalyst loading (3 mol % Pd(OAc)2 and 6 mol % 6a). At high temperature, the catalyst loading can be lowered to 0.01e0.1 mol % for reactions of aryl bromides and chlorides with a variety of arylboronic acids to generate the corresponding

products in good to excellent yields. The mechanism of the reaction is under investigation currently in our lab. 4. Experimental section 4.1. General Unless otherwise noted, all reactions were performed in an ovendried glasswares under an Ar atmosphere. Commercially obtained reagents were used without further purification. All solvents were purified by standard methods. 1H, 13C, and 19F NMR spectra were recorded on 300 MHz (or 400 MHz), 100.5 MHz, and 282 MHz spectrometer. 1H NMR and 13C NMR chemical shifts were determined relative to internal standard TMS at d 0.0 and 19F NMR chemical shifts were determined relative to CFCl3 as internal standard. All reactions were monitored by TLC or 19F NMR spectroscopy. Flash column chromatography was performed on silica gel (300e400 mesh) unless otherwise stated. 4.2. Preparation of 2,4,6-tribromo-N-acetylaniline 1 2,4,6-Tribromoaninile (60 g, 180 mmol) was added to acetic anhydride (400 mL) in a three-neck round-bottom flask equipped with a mechanic stirrer, a thermometer, and a reflux condenser. The mixture was stirred and the temperature increased quickly. A few drops of sulfuric acid was added when the temperature was dropped to 60  C. The mixture was allowed to stir for 6 h and was cooled to room temperature. The solid was filtered and recrystallized from ethanol to give 2,4,6-tribromo-N-acetylaniline 1 (58 g, 87%). 1H NMR (300 M, DMSO-d6) d 2.03 (s, 3H), 8.01 (s, 2H), 9.91 (s, 1H). 4.2.1. N-[2,4,6-Tri-(3,3,3-trifluoro-1-propenyl)-phenyl]-act-amide 3. Into a three-neck round-bottom flask were added 2,4,6tribromo-N-acetylaniline (30.0 g, 80.6 mmol), Pd(OAc)2 (2.70 g,

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T. Liu et al. / Tetrahedron 68 (2012) 6535e6547

Table 5 SuzukieMiyaura coupling of heteroaryl substratesa Entry

Aryl chloride

Arylboronic acid

Yieldb (%)

Product

B(OH)2 1

MeO

MeO

Cl

S

S B(OH)2

OMe

B(OH)2

4

10c

85

10d

94

10e

95

10f

87

10g

90

10h

89

10i

82

10j

85

10k

85

10l

92

10m

82

10n

97

S

S B(OH)2

O

95

Me

3

Cl

10b

S

S

Me

92

OMe

2

Cl

10a

O

Cl

S

S B(OH)2 5

Me

Me

Cl

S

S B(OH)2

Cl 6

N

S

N

S B(OH)2

7

Me

Me

Cl

S

S

S

S

OMe

OMe

B(OH)2

8

Cl

N

N B(OH)2

9

S

Cl

N

S

N

Cl

B(OH)2

10

N

11

N

N

MeO

Cl

Cl

B(OH)2

O

N

OMe O

MeO

OMe

12

B(OH)2

N Cl

N Me

Me

13

B(OH)2

N

N F

F 14

B(OH)2

N

Cl

N

T. Liu et al. / Tetrahedron 68 (2012) 6535e6547

6541

Table 5 (continued ) Entry

Aryl chloride

15

Arylboronic acid

B(OH)2

Cl

S

S

Cl

S

B(OH)2

Cl

18

Cl

a b

S

Me

Ph

B(OH)2

S

86

10q

92

10r

43

N

Ph

Me

10p

N Et

N

88

S

B(OH)2

N Et

17

10o

MeO

OMe 16

Yieldb (%)

Product

Cl

Me Ph

S

Me

S

Ph

Standard conditions: Pd(OAc)2 (3 mol %), 6a (6 mol %), aryl chloride (0.8 mmol), aryl boronic acid (1.2 mmol), K3PO4 (2.8 mmol), THF/H2O (5:1), reflux, 12 h. Isolated yield.

12.1 mmol), NaOAc (33.0 g, 403 mmol), n-Bu4NBr (55.0 g, 242 mmol), and DMF (200 mL) under argon atmosphere. The atmosphere was exchanged three times with 3,3,3-trifluoropropene. The mixture was vigorously stirred for 24 h at 120  C and then allowed to cool to room temperature. The solvent was removed under vacuum. The residue was dissolved in ethyl acetate (100 mL) and washed with water (200 mL). The organic layer was separated and dried over Na2SO4. The solvent was removed under vacuum and the residue was purified by flash chromatography (Et2O as the eluent) to give the desired product as a white solid. Mp 239e240  C. 1 H NMR (300 MHz, CD3OD) d 2.24 (s, 3H), 6.57e6.80 (m, 3H), 7.26e7.36 (m, 3H), 8.03 (s, 2H). 19F NMR (CD3OD) d 65.42 (dd, J¼2.0 Hz, 7.3 Hz, 6F), 65.15 (dd, J¼2.0 Hz, 7.3 Hz, 3F); 13C NMR (CD3OD) d 20.5, 117.2 (q, J¼28.4 Hz), 118.5 (q, J¼28.4 Hz), 123.0 (q, J¼268 Hz), 123.1 (q, J¼268 Hz), 126.5, 123.1, 123.2, 133.1, 135.0, 135.5, 170.8. MS (EI) m/z 417 (14), 375 (100), 356 (4), 334 (5), 316 (23), 266 (24), 43(41). IR (film, cm1) n 3246, 1669, 1585, 1515, 1465, 1437, 1378, 1303, 1281, 1116, 973. HRMS for C17H13F9NO (MþHþ): calcd 418.0848, found 418.0855. 4.2.2. 2,4,6-Tri(3,3,3-trifluoro-1-propyl)aniline 4. Into a roundbottom flask were added 2,4,6-tri-(3,3,3-trifluoro-1-propenyl)acetylaniline (8.0 g, 19.2 mmol), Pd/C (10%, 400 mg), and EtOAc (100 mL). Hydrogen was bubbled into the mixture for 30 min and a balloon containing hydrogen gas was connected to the reaction system. The mixture was stirred at room temperature for 24 h. The mixture was filtered and washed with ethyl acetate (10 mL3). The solvent was removed under vacuum and the residue was used directly without further purification. The solid obtained from the previous step was dissolved in methylene chloride (200 mL). MeO3$BF4 (3.6 g, 24 mmol) was added dropwise. The mixture was stirred at room temperature for 12 h until the disappearance of the starting material as determined by TLC. To the mixture was added CF3CO2H (20 mL) and methanol (10 mL). The resulted mixture was allowed to stir for 2 h. The pH of the mixed solution was adjusted to 8e9 with saturated aqueous NaHCO3. The organic layer was separated and the water phase was washed with ethyl acetate (10 mL3). The organic phase was combined and dried over Na2SO4. The solvent was removed under vacuum and the residue was purified by flash

chromatography (petroleum ether/ethyl acetate¼50:1 as the eluent) to give the desired product 4 as a white solid (4.5 g, 58%). Mp 145e146  C. 1H NMR (300 MHz, CDCl3) d 2.28e2.44 (m, 6H), 2.72e2.77 (m, 6H), 3.57 (s, 2H), 6.81 (s, 2H); 19F NMR (CDCl3) d 67.23 (t, J¼11.0 Hz, 6F), 67.04 (t, J¼11.0 Hz, 3F); 13C NMR (CDCl3) d 24.2, 27.3, 33.0 (q, J¼28.4 Hz), 36.0 (q, J¼28.4 Hz), 121.2, 126.6 (q, J¼276.7 Hz), 126.7 (q, J¼276.7 Hz), 128.5, 129.4, 140.1. MS (ESI) m/z 382.1 (MþHþ). IR (film, cm1) n 3425, 2989, 1635, 1613, 1489, 1463, 1383, 1313, 1254, 1134, 1091, 989. HRMS for C15H17F9N (MþHþ): calcd 382.1211, found 382.1211. Anal. Calcd for C15H16F9N: C, 47.25; H, 4.23; N, 3.67. Found: C, 47.39; H, 4.00; N, 3.42. 4.2.3. N,N 0 -Bis-[2,4,6-tri(3,3,3-trifluoro-propyl)phenyl]-1,4diazadiene 5. To a mixture of aniline (2.3 g, 6.0 mmol) and glyoxal (3 mol, 40% aqueous solution) in methanol was added a few drops of formic acid. The mixture was stirred at room temperature for 24 h, and the yellow precipitations appeared. After the reaction was completed, the solid was filtered, washed with methanol, and dried under vacuum to give N,N0 -bis-[2,4,6-tri(3,3,3-trifluoro-propyl) phenyl]-1,4-diazadiene 5 (2.0 g, 85%) as yellow solid. Mp 126e128  C. 1H NMR (300 MHz, CDCl3) d 2.26e2.44 (m, 12H), 2.71e276 (m, 6H), 2.82e2.87 (m, 3H), 7.00 (s, 4H), 8.13 (s, 2H). 19F NMR (CDCl3) d 67.49 (t, J¼11.0 Hz, 12 F), 66.98 (t, J¼11.0 Hz, 6F). 13 C NMR (CDCl3) d 22.8, 27.6, 33.7 (q, J¼28.8 Hz), 35.6 (q, J¼28.8 Hz), 126.5 (q, J¼276.7 Hz), 126.6 (q, J¼276.7 Hz), 128.3, 128.4, 136.5, 147.8, 163.5. MS (ESI) m/z 785.2 (MþHþ). IR (film, cm1): n 2983, 2934, 1639, 1456, 1385, 1311, 1251, 1223, 1151, 1132, 1097, 993. Anal. Calcd for C32H30F18N2: C, 48.99; H, 3.85; N, 3.57. Found: C, 49.13; H, 4.09; N, 3.34. 4.2.4. N,N0 -Bis-[2,4,6-tri(3,3,3-trifluoro-propyl)phenyl]-ethylene-diamine 5a. To a solution of N,N0 -bis-[2,4,6-tri(3,3,3-trifluoro-propyl)-phenyl]-1,4-diazadiene (552 mg, 0.7 mmol) in 20 mL of MeOH/THF (2:3) was added NaBH4 (267 mg, 7 mmol). The yellow color of the reaction mixture turned into white after 1.5 h. The reaction was quenched by a saturated aqueous NH4Cl. The resulting mixture was extracted with ether, and washed with deionized water. The organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure to afford the diamine

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Table 6 .SuzukieMiyaura coupling at low catalyst loadinga Entry

Aryl halide

Arylboronic acid

Loading (mol %)

Yieldb (%)

11a

0.01

75

11b

0.01

95

11c

0.01

95

11d

0.01

91

11e

0.1

69

11f

0.1

99

11g

0.1

76

11h

0.01

98

11i

0.01

97

0.01

84

0.003

64

11k

0.05

98

11l

0.05

63

11m

0.05

45

Product

OMe

OMe

1

B(OH)2

Br OMe

OMe

t-Bu

2

Br

B(OH)2

tBu

OMe

OMe

3

Me

Br OMe

B(OH)2

Me OMe

Me

4

Br

B(OH)2

Me

OMe

OMe

CF3

5

Br

B(OH)2 F3C

OMe

OMe

F3C

6

Br

B(OH)2 CF3

Br 7

B(OH)2

N

N

8

Br

B(OH)2

O

9

O

F3C

O

Br

B(OH)2

Br

B(OH)2

CF3

O

10

Cl

11j

Cl

11

11

O

O

B(OH)2

Cl

CN

CN 12

B(OH)2

Cl

13

a b

Me

Cl

MeO

B(OH)2

Me

OMe

Standard conditions: Pd(OAc)2/6a as indicated in the table, aryl chloride (0.8 mmol), aryl boronic acid (1.2 mmol), K3PO4 (2.8 mmol), THF/H2O (5:1), reflux, 12 h. Isolated yield.

T. Liu et al. / Tetrahedron 68 (2012) 6535e6547

derivative 5a (525 mg, 95%) as a white solid. Mp 102e103  C. 1H NMR (300 MHz, CDCl3) d 2.32e2.44 (m, 12H), 2.77e2.83 (m, 3H), 2.89e2.93 (m, 6H), 3.14 (s, 4H), 6.92 (s, 4H); 19F NMR (CDCl3) d 66.9 (t, J¼11.0 Hz, 6F), 66.6 (t, J¼11.0 Hz, 12 F); 13C NMR (CDCl3) d 23.5, 27.0, 34.3 (q, J¼28.3 Hz), 35.1 (q, J¼28.3 Hz), 50.34, 126.0 (q, J¼276.6 Hz), 126.1 (q, J¼276.6 Hz), 127.7, 133.5, 134.8, 142.2. MS (ESI) m/z 789.2 (MþHþ). IR (film, cm1) n 2955, 1479, 1468, 1380, 1306, 1253, 1225, 1144, 1095, 1033, 990. Anal. Calcd for C32H34F18N2: C, 48.74; H, 4.35; N, 3.55. Found: C, 48.95; H, 4.42; N, 3.36. 4.2.5. N,N 0 -Bis-[2,4,6-tri(3,3,3-trifluoro-propyl)phenyl]-4,5dihydroimidazolium chloride 6a. A mixture of diamine (8.5 g, 22 mmol), NH4Cl (1.33 g, 25 mmol), and triethyl orthoformate (8.35 g, 56.0 mmol) was stirred at 110  C for 1.5 h under argon flow (to drive out EtOH from the reaction system). After the reaction was completed, the solid was filtered and recrystallized from CHCl3/ ether to give N,N0 -bis-[2,4,6-tri(3,3,3-trifluoro-propyl)phenyl]-4,5dihydroimidazolium chloride 5.53 g (57%) as a white solid. Mp 217e221  C. 1H NMR (300 MHz, CDCl3) d 2.39e2.66 (m, 8H), 2.68e2.92 (m, 12H), 3.02e3.21 (m, 4H), 4.38 (s, 4H), 7.11 (s, 4H), 11.76 (s, 1H); 19F NMR (CDCl3) d 66.4 (t, J¼10.8 Hz, 6F), 66.2 (dd, J¼10.8 Hz, 12F); 13C NMR (CDCl3) d 23.0, 27.5, 33.6 (q, J¼28.8 Hz), 34.5 (q, J¼28.8 Hz), 51.9, 125.8 (q, J¼276.2 Hz), 126.0 (q, J¼276.2 Hz), 127.7, 136.8, 142.2, 162.8. IR (film, cm1) n 2952, 1625, 1604, 1446, 1390, 1311, 1256, 1134, 1103, 980. MS (ESI) m/z 799.3 (MCl). HRMS for C33H33F18N2 (MCl): calcd 799.2350, found 799.2322. 4.3. Preparation of 1,3,5-trialkylbenzene 1-Bromopropane (25 g, 0.20 mol) was added dropwise to a mixture of Mg (5.0 g, 0.21 mol) in diethyl ether (100 mL) at room temperature. The mixture was refluxed for 2 h and then cooled to room temperature. The new prepared Grignard reagent was then added to a mixture of 1,3,5-trichlorobenzene (10.4 g, 570 mmol) and Ni(dppe)Cl2 (75 mg, 0.14 mmol) in 100 mL of diethyl ether at room temperature. The mixture was stirred overnight and quenched by adding a saturated aqueous NH4Cl. The resulting mixture was extracted with ether, and washed with deionized water. The organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography to give 1,3,5-trialkylbenzene (9.75 g, 84%) as a colorless oil. 4.3.1. 1,3,5-Tripropylbenzene. Colorless oil. Yield 84%. 1H NMR (300 MHz, CDCl3) d 0.68 (t, J¼8.5 Hz, 9H), 1.37 (m, 6H), 2.29 (t, J¼7.5 Hz, 6H), 6.59 (s, 3H). 4.3.2. 1,3,5-Tributylbenzene. Colorless oil. Yield 79%. 1H NMR (300 MHz, CDCl3) d 0.92 (t, J¼6.9 Hz, 9H), 1.32e1.39 (m, 6H), 1.56e1.61 (m, 6H), 2.54 (t, J¼7.5 Hz, 6H), 6.81 (s, 3H). 4.3.3. 1,3,5-Tri-iso-pentylbenzene. Colorless oil. Yield 92%. 1H NMR (300 MHz, CDCl3) d 0.92 (d, J¼6.3 Hz, 18H), 1.41e1.53 (m, 9H), 2.54 (t, J¼8.4 Hz, 6H), 6.81 (s, 3H).

4.4. Preparation of 2,4,6-trialkyl-1-nitrobenzene A mixture of HNO3 (5.0 mL) and HOAc (5.0 mL) was added dropwise to a solution of 1,3,5-tripropylbenzene (9.7 g, 0.047 mol) in acetic anhydride (15.0 mL) at 0  C. The mixture was stirred for 3 h at room temperature before being dumped into ice/water (200 mL). The mixture was then extracted with ether, and washed with deionized water. The organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure and

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the residue was purified by flash chromatography to give 2,4,6tripropyl-1-nitrobenzene (8.7 g, 74%) as a colorless oil. 4.4.1. 2,4,6-Tripropyl-1-nitrobenzene. Colorless oil. Yield 74%. IR (film, cm1): n 2964, 2935, 2875, 1600, 1568, 1527, 1467, 1371, 833. 1H NMR (300 MHz, CDCl3) d 0.87 (t, J¼6.9 Hz, 9H), 1.48e1.62 (m, 6H), 2.41e2.52 (m, 6H), 6.87 (s, 2H). 13C NMR (CDCl3) d 13.6, 13.8, 23.9, 24.2, 33.3, 37.5, 127.8, 133.3, 144.5, 149.6. MS (EI) m/z 249 (4.7), 232 (35), 204 (13), 176 (77), 91 (40), 43 (50). HRMS: exact mass calcd C15H23NO2 (Mþ): 249.1729, found 249.1732. Anal. Calcd for C15H23NO2: C, 72.25; H, 9.03; N, 5.62. Found: C, 72.24; H, 9.31; N, 5.89. 4.4.2. 2,4,6-Tributyl-1-nitrobenzene. Colorless oil. Yield 69%. IR (film, cm1): n 2960, 2933, 2874, 1600, 1527, 1466, 1371, 1106, 838. 1 H NMR (300 MHz, CDCl3) d 0.88e0.96 (m, 9H), 1.28e1.40 (m, 6H), 1.52e1.63 (m, 6H), 2.49e2.60 (m, 6H), 6.93 (s, 2H). 13C NMR (CDCl3) d 13.7, 13.8, 22.2, 22.5, 31.1, 32.9, 33.3, 35.3, 127.7, 133.7, 144.8, 149.5. MS (EI) m/z 291 (13), 274 (100), 204 (64), 162 (29), 71 (23), 43 (13). Anal. Calcd for C18H29NO2: C, 74.18; H, 10.03; N, 4.81. Found: C, 74.26; H, 10.03; N, 4.81. 4.4.3. 2,4,6-Tri-iso-pentyl-1-nitrobenzene. Colorless oil. Yield 59%. IR (film, cm1): n 2958, 2872, 1600, 1527, 1468, 1386, 1369, 1170, 875, 840. 1H NMR (300 MHz, CDCl3) d 0.90e0.98 (m, 18H), 1.43e1.62 (m, 9H), 2.47e2.60 (m, 6H), 6.91 (s, 2H). 13C NMR (CDCl3) d 22.3, 22.4, 27.7, 28.0, 29.4, 33.5, 40.1, 40.5, 127.6, 134.1, 145.2, 149.4. MS (EI) m/z 333 (15), 316 (63), 288 (13), 277 (18), 206 (100), 43 (31). Anal. Calcd for C21H35NO2: C, 75.63; H, 10.58; N, 4.20. Found: C, 75.43; H, 10.45; N, 4.24. 4.5. Preparation of 2,4,6-trialkylaniline 4 A mixture of 2,4,6-tripropyl-1-nitrobenzene (4.72 g 19.0 mmol), ammonia chloride (2.0 g, 37.9 mmol), zinc (8.94 g, 137 mmol) and water (150 mL) was stirred at 100  C for 4 h. The mixture was cooled to room temperature. The solid was filtered and the aqueous solution was extracted by diethyl ether. The organic layer was combined and washed with deionized water, and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography to give 2,4,6tripropylaniline (2.9 g, 69%) as a colorless oil. 4.5.1. 2,4,6-Tripropylaniline 4b. Colorless oil. IR (film, cm1): n 3475, 3387, 3003, 2985, 2931, 2871, 1625, 1604, 1479, 1378, 853. 1H NMR (300 MHz, CDCl3) d 1.00e1.13 (m, 9H), 1.63e1.81 (m, 6H), 2.54e2.59 (m, 6H), 3.57 (br, 2H), 6.87 (s, 2H). 13C NMR (CDCl3) d 14.0, 14.4, 22.1, 25.1, 34.0, 37.6, 126.6, 127.3, 132.2, 139.5. MS (ESI) m/z 220 (MþHþ). Anal. Calcd for C15H25N: C, 82.13; H, 11.49; N, 6.39. Found: C, 82.44; H, 11.75; N, 6.53. 4.5.2. 2,4,6-Tributylaniline 4c. Colorless oil. 82% yield. IR (film, cm1): n 3477, 3388, 3003, 2958, 2929, 2872, 2860, 1625, 1604, 1479, 1378, 863. 1H NMR (300 MHz, CDCl3) d 0.81e0.90 (m, 9H), 1.20e1.39 (m, 12H), 2.37e2.42 (m, 6H), 3.40 (br, 2H), 6.67 (s, 2H). 13 C NMR (CDCl3) d 13.9, 22.4, 22.8, 31.1, 31.4, 34.1, 34.9, 126.7, 127.0, 132.4, 139.2. MS (EI) m/z 261 (31), 218 (100). Anal. Calcd for C18H31N: C, 82.69; H, 11.95; N, 5.36. Found: C, 82.66; H, 11.95; N, 5.13. 4.5.3. 2,4,6-Tri-iso-pentylaniline 4d. Colorless oil. 73% yield. IR (film, cm1): n 3477, 3381, 3003, 2955, 2930, 2870, 1624, 1603, 1479, 1468, 1384, 1367, 872. 1H NMR (300 MHz, CDCl3) d 0.89e1.02 (m, 18H), 1.40e1.69 (m, 9H), 2.41e2.52 (m, 6H), 3.38 (br, 2H), 6.75 (s, 2H). 13C NMR (CDCl3) d 22.5, 27.8, 28.2, 29.6, 33.1, 38.1, 41.3, 126.8, 127.0, 132.8, 139.1. MS (EI) m/z 303 (54), 246 (100). Anal. Calcd for

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T. Liu et al. / Tetrahedron 68 (2012) 6535e6547

C21H37N: C, 83.10; H, 12.29; N, 4.61. Found: C, 83.09; H, 12.07; N, 4.48. 4.6. Preparation of N,N0 -bis-[2,4,6-trialkylphenyl]-1,4diazadiene 5 Two drops of formic acid were added to a mixture of 2,4,6tripropylaniline (2.4 g, 11 mmol) and glyoxal (1.1 g, 5.5 mmol, 40% aqueous solution) in methanol (20 mL). The mixture was stirred at room temperature overnight. The products were precipitated from the reaction mixture as a yellow solid or oil and were used without further purification. 5b. Yellow 4.6.1. N,N0 -Bis-[2,4,6-tripropylphenyl]-1,4-diazadiene solid. Mp 69e70  C. IR (film, cm1): n 2959, 2931, 2871, 1630, 1464, 1377, 1226, 1198, 850. 1H NMR (300 MHz, CDCl3) d 0.82e0.98 (m, 18H), 1.42e1.70 (m, 12H), 2.44 (t, J¼7.6 Hz, 6H), 2.53 (t, J¼7.6 Hz, 6H), 7.08 (s, 4H), 8.09 (s, 2H). 13C NMR (CDCl3) d 13.9, 14.1, 23.7, 24.6, 33.8, 37.6, 127.4, 130.7, 138.7, 147.3, 163.3. Anal. Calcd for C32H48N2: C, 83.42; H, 10.50; N, 6.08. Found: C, 83.30; H, 10.75; N, 5.95. 4.6.2. N,N0 -Bis-[2,4,6-tributylphenyl]-1,4-diazadiene 5c. Yellow oil. 83% yield. IR (film, cm1): n 2958, 2931, 2872, 2860, 1629, 1463, 1378, 1207, 1140, 862. 1H NMR (300 MHz, CDCl3) d 0.72e0.99 (m, 18H), 1.28e1.41 (m, 12H), 1.44e1.65 (m, 12H), 2.45 (t, J¼7.8 Hz, 6H), 2.56 (t, J¼7.8 Hz, 6H), 6.89 (s, 4H), 8.10 (s, 2H). 13C NMR (CDCl3) d 13.9, 14.0, 22.4, 22.7, 31.3, 32.8, 33.7, 35.2, 127.2, 130.9, 139.0, 147.2, 163.3. Anal. Calcd for C38H60N2: C, 83.76; H, 11.10; N, 5.14. Found: C, 83.80; H, 11.07; N, 4.99. 4.6.3. N,N 0 -Bis-[2,4,6-tri-iso-pentylphenyl]-1,4-diazadiene 5d. Yellow solid. Mp 41e42  C, 64% yield. IR (film, cm1): n 2955, 2929, 2869, 1631, 1577, 1467, 1383, 1366, 1207, 871. 1H NMR (CDCl3, 300 MHz) d 0.89 (d, J¼6.4 Hz, 24H), 0.95 (d, J¼6.4 Hz, 12H), 1.37e1.64 (m, 18H), 2.44 (t, J¼8.2 Hz, 6H), 2.55 (t, J¼8.2 Hz, 6H), 6.89 (s, 4H), 8.10 (s, 2H). 13C NMR (CDCl3) d 22.5, 27.9, 28.1, 29.4, 33.4, 39.9, 40.9, 127.0, 131.3, 139.4, 147.0, 163.2. MS (ESI) m/z 629 (MþHþ). Anal. Calcd for C44H72N2: C, 84.01; H, 11.54; N, 4.45. Found: C, 84.31; H, 11.41; N, 4.18. 4.7. Preparation of N,N0 -bis-(2,4,6-trialkylphenyl)ethylenediamine To a solution of N,N0 -bis-(2,4,6-tripropylphenyl)-1,4-diazadiene obtained from the previous step in 50 mL of MeOH/THF (2:3) was added NaBH4 (4 g). The yellow color of the reaction mixture turned into white after 1.5 h. The reaction was quenched by a saturated aqueous NH4Cl. The resulting mixture was extracted with ether, and washed with deionized water. The organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure to afford the diamine derivative. 4 . 7 .1. N , N 0 - B i s - ( 2 , 4 , 6 - t r i p r o p yl p h e n yl ) - e t h yl e n e d i a m i n e 7b. Colorless oil. 69% yield. IR (film, cm1): n 2959, 2930, 2871, 1466, 1416, 1378, 1234, 1091. 1H NMR (300 MHz, CDCl3) d 0.81e0.97 (m, 18H), 1.41e1.62 (m, 12H), 2.41 (t, J¼7.6 Hz, 6H), 2.54 (t, J¼7.6 Hz, 6H), 3.05 (s, 4H), 6.74 (s, 4H). 13C NMR (CDCl3) d 13.9, 14.3, 24.0, 24.6, 33.8, 37.6, 51.0, 127.6, 135.2, 136.7, 142.7. MS (ESI) m/z 465 (MþHþ). HRMS: exact mass calcd C32H53N2: 465.4203, found 465.4214. 4.7.2. N,N0 -Bis-(2,4,6-tributylphenyl)-ethylenediamine 7c. Colorless oil. Without further purification and used directly in the next step. IR (film, cm1): n 3366, 2957, 2929, 2860, 1467, 1415, 1224, 862. 1H NMR (300 MHz, CDCl3) d 0.85 (t, J¼7.2 Hz, 18H),

1.21e1.39 (m, 12H), 1.41e1.59 (m, 12H), 2.43 (t, J¼7.8 Hz, 6H), 2.55 (t, J¼7.8 Hz, 6H), 3.04 (s, 4H), 6.76 (s, 4H). 13C NMR (CDCl3) d 14.0, 14.1, 22.5, 22.9, 31.4, 33.2, 33.8, 35.2, 51.0, 127.4, 135.5, 137.0, 142.6. MS (ESI) m/z 549 (MþHþ). Anal. Calcd for C38H64N2: C, 83.15; H, 11.75; N, 5.10. Found: C, 82.96; H, 11.57; N, 4.94. 4.7.3. N,N 0 -Bis-(2,4,6-tri-iso-pentylphenyl)-ethylenediamine 7d. Colorless oil. Without further purification and used directly in the next step. IR (film, cm1): n 3365, 2955, 2931, 2870, 1625, 1468, 1384, 1367, 1224, 872. 1H NMR (300 MHz, CDCl3) d 0.82e0.96 (m, 36H), 1.36e1.60 (m, 18H), 2.38e2.43 (m, 6H), 2.44e2.60 (m, 6H), 3.04 (s, 4H), 6.76 (s, 4H). 13C NMR (CDCl3) d 22.6, 22.7, 27.9, 28.3, 29.5, 33.3, 40.4, 41.0, 51.1, 127.3, 136.0, 137.3, 142.5. MS (EI) m/z 303 (53), 246 (100). Anal. Calcd for C44H76N2: C, 83.48; H, 12.10; N, 4.42. Found: C, 83.74; H, 12.33; N, 4.31. 4.7.4. N,N 0 -Bis-((2,4,6-trialkyl)phenyl)-4,5-dihydroimidazolium chloride 8. A mixture of diamine (1.53 g, 3.3 mmol), NH4Cl (185 mg, 3.46 mmol), and triethyl orthoformate (1.22 g, 8.25 mmol) was stirred at 110  C for 1.5 h under argon flow (to drive out EtOH from the reaction system). After the reaction was completed, the solid was filtered and recrystallized from CHCl3/ether to give N,N0 -bis((2,4,6-tripropyl)phenyl)-4,5-dihydroimidazolium chloride 0.93 g (69%) as a white solid. 4.7.5. N,N0 -Bis-((2,4,6-tripropyl)phenyl)-4,5-dihydroimidazolium chloride 8a. White solid. Mp 271e273  C, 69% yield. IR (film, cm1): n 2960, 2932, 2870, 2758, 1619, 1597, 1465, 1252, 1093, 860. 1H NMR (CDCl3, 300 MHz, TMS) d 0.94 (t, J¼7.2 Hz, 6H), 1.03 (t, J¼7.2 Hz, 12H), 1.52e1.61 (m, 12H), 2.51e2.62 (m, 12H), 4.77 (s, 4H), 7.00 (s, 4H), 8.19 (s, 1H). 13C NMR (CDCl3) d 13.7, 14.2, 24.0, 24.3, 30.9, 33.2, 37.7, 54.3, 128.1, 129.2, 139.2, 145.5, 158.3. MS (ESI) m/z 475 (MCl). HRMS: exact mass calcd C33H51N2: 475.4046, found 475.4060. 4.7.6. N,N 0 -Bis-((2,4,6-tributyl)phenyl)-4,5-dihydroimidazolium chloride 8b. White solid. Mp 142e144  C, 41% yield. IR (film, cm1): n 2957, 2931, 2750, 1605, 1529, 1466, 1376, 1222, 1047, 766. 1H NMR (300 MHz, CDCl3) d 0.91e1.01 (m, 18H), 1.28e1.48 (m, 12H), 1.51e1.69 (m, 12H), 2.56e2.65 (m, 12H), 4.74 (s, 4H), 7.00 (s, 4H), 8.17 (s, 1H). 13C NMR (CDCl3) d 13.7, 13.9, 22.2, 2.7, 30.8, 32.9, 33.2, 35.3, 54.1, 127.8, 128.9, 139.3, 145.7, 158.2. MS (ESI) m/z 559 (MCl). HRMS: exact mass calcd C39H64N2: 560.5064, found 560.5065. 4 . 7 . 7 . N , N 0- B i s - ( ( 2 , 4 , 6 - t r i - i s o - p r o p y l ) p h e n y l ) - 4 , 5 dihydroimidazolium chloride 8d. White solid. Mp 163e167  C, 45% yield. IR (film, cm1): n 2954, 2868, 2794, 1620, 1598, 1468, 1384, 1366, 1266, 875. 1H NMR (300 MHz, CDCl3) d 0.90e1.00 (m, 36H), 1.44e1.71 (m, 18H), 2.56e2.66 (m, 12H), 4.69 (s, 4H), 6.99 (s, 4H), 8.52 (s, 1H). 13C NMR (CDCl3) d 22.4, 22.6, 27.7, 28.1, 28.9, 33.6, 39.9, 40.4, 53.9, 127.7, 128.9, 139.6, 145.9, 158.9. MS (ESI) m/z 643.8 (MCl). HRMS: exact mass calcd C45H76N2: 644.6003, found 644.5984. 4.7.8. N,N0 -Bis-((2,4,6-tripropyl)phenyl)-4,5-imidazolium chloride 6b. White solid. Mp 142e144  C, 32% yield. 1H NMR (300 MHz, CDCl3) d 0.90e1.00 (m, 18H), 1.52e1.72 (m, 12H), 2.27e2.59 (m, 8H), 2.62 (t, J¼7.6 Hz, 4H), 7.07 (s, 4H), 7.98 (s, 2H), 9.96 (s, 1H). 13 C NMR (CDCl3) d 13.8, 14.1, 23.8, 24.3, 33.3, 37.8, 126.2, 128.1, 129.7, 138.4, 138.6, 146.2. MS (ESI) m/z 473 (MCl). 4.7.9. N,N0 -Bis-((2,4,6-tributyl)phenyl)-4,5-imidazolium chloride 6c. White solid. Mp 201e203  C, 39% yield. IR (film, cm1): n 2958, 2931, 2781, 1617, 1595, 1466, 1377, 1257, 1169, 866. 1H NMR

T. Liu et al. / Tetrahedron 68 (2012) 6535e6547

(CDCl3, 300 MHz) d 0.88e1.01 (m, 18H), 1.25e1.65 (m, 24H), 2.27e2.47 (m, 8H), 2.64 (t, J¼7.8 Hz, 4H), 7.06 (s, 4H), 7.95 (s, 2H), 9.84 (s, 1H). 13C NMR (CDCl3) d 13.8, 22.4, 22.6, 30.9, 32.7, 33.2, 35.5, 126.0, 127.9, 129.5, 138.5, 138.6, 146.4. MS (ESI) m/z 557.6 (MCl). HRMS: exact mass calcd C39H62N2: 558.4907, found 558.4885. 4.7.10. N,N0 -Bis-((2,4,6-tri-iso-pentyl)phenyl)-4,5-imidazolium chloride 6d. White solid. Mp 168e173  C, 37% yield. IR (film, cm1): n 2956, 2870, 1650, 1533, 1468, 1385, 1367, 1227, 874. 1H NMR (300 MHz, CDCl3) d 0.89 (d, J¼6.8 Hz, 24H), 0.96 (d, J¼6.8 Hz, 12H), 1.28e1.58 (m, 18H), 2.20e2.65 (m, 12H), 7.05 (s, 4H), 7.79 (s, 2H), 10.3 (s, 1H). 13C NMR (CDCl3) d 22.4, 22.5, 27.8, 27.9, 29.0, 33.7, 39.7, 40.4, 125.3, 127.6, 129.5, 138.9, 139.7, 146.6. MS (ESI) m/z 641.9 (MCl). HRMS: exact mass calcd C45H76N2: 642.5846, found 642.5929. 4.7.11. N,N0 -Bis-((2,4,6-trimethyl)phenyl)-4,5-imidazolium chloride 6e. White solid. 53% yield. 1H NMR (300 MHz, CDCl3) d 2.18 (s, 12H), 2.35 (s, 6H), 7.02 (s, 4H), 7.66 (s, 2H), 10.66 (s, 1H). MS (ESI) m/z 305.3 (MCl). 4.8. General method for the SuzukieMiyaura reaction of aryl chlorides or aryl triflates at room temperature In a schlenk tube with a magnetic bar, 6a (40 mg, 6 mol %), Pd(OAc)2 (5.4 mg, 3 mol %), and K3PO4 (594 mg, 2.8 mmol) in 5 mL of THF/H2O (5:1) were placed under argon. Aryl chloride (0.8 mmol) was added via syringe and followed by adding phenylboronic acid (1.2 mmol). The resulting mixture was stirred at room temperature for 12 h. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (petroleum ether/EtOAc¼100:1) to give the desired product. 4.8.1. 4-Methoxybiphenyl14 9a (Table 3, entry 1). The general procedure afforded 92% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.85 (s, 3H), 6.98 (d, J¼8.1 Hz, 2H), 7.26e7.30 (m, 1H), 7.39e7.44 (m, 2H), 7.52e7.57 (m, 4H). 4.8.2. 4-Methoxy-20 -methylbiphenyl5a 9b (Table 3, entry 2). The general procedure afforded 98% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.43 (s, 3H), 3.96 (s, 3H), 7.08e7.11 (m, 2H), 7.38e7.42 (m, 6H). 4.8.3. 4-Methoxy-30 -trifluoromethylbiphenyl14 9c (Table 3, entry 3). The general procedure afforded 95% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.91 (s, 3H), 7.08 (d, J¼9.0 Hz, 2H), 7.54e7.66 (m, 4H), 7.76e7.79 (m, 1H), 7.90e7.92 (m, 1H). 4.8.4. 2,40 -Dimethoxybiphenyl13 9d (Table 3, entry 4). The general procedure afforded 95% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.73 (s, 3H), 3.76 (s, 3H), 6.86e6.93 (m, 4H), 7.16e7.24 (m, 2H), 7.39 (d, J¼9.0 Hz, 2H). 4.8.5. 4-tert-Butyl-40 -methoxybiphenyl19 9e (Table 3, entry 5). The general procedure afforded 91% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 1.36 (s, 9H), 3.84 (s, 3H), 6.96 (d, J¼8.9 Hz, 2H), 7.41e7.53 (m, 6H). 4.8.6. 4-Methylbiphenyl5a 9f (Table 3, entry 6). The general procedure afforded 94% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.53 (s, 3H), 7.37e7.58 (m, 5H), 7.64 (d, J¼8.1 Hz, 2H), 7.73 (d, J¼7.5 Hz, 2H). 4.8.7. 2-Methoxylbiphenyl14 9g (Table 3, entry 7). The general procedure afforded 93% of the title compound. 1H NMR (CDCl3,

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300 MHz, TMS) d 3.97 (s, 3H), 7.16e7.25 (m, 2H), 7.54e7.66 (m, 5H), 7.78 (d, J¼7.5 Hz, 2H). 4.8.8. 2-Methoxyl-20 -methylbiphenyl5a 9h (Table 3, entry 8). The general procedure afforded 96% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.34 (s, 3H), 3.91 (s, 3H), 7.11e7.20 (m, 2H), 7.32e7.52 (m, 6H). 4.8.9. 2-Methoxyl-20 -methylbiphenyl5a 9i (Table 3, entry 9). The general procedure afforded 96% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.34 (s, 3H), 3.91 (s, 3H), 7.11e7.20 (m, 2H), 7.32e7.52 (m, 6H). 4.8.10. 3-Methoxylbiphenyl5a 9j (Table 3, entry 10). The general procedure afforded 96% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.97 (s, 3H), 7.04e7.07 (m, 1H), 7.32e7.36 (m, 2H), 7.50e7.58 (m, 4H), 7.74e7.76 (m, 2H). 4.8.11. 4-Methoxy-20 ,20 -dimethylbiphenyl16 9k (Table 3, entry 11). The general procedure afforded 84% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.04 (s, 6H), 3.85 (s, 3H), 6.95e7.10 (m, 7H). 4.8.12. 2-Methoxy-20 ,20 -dimethylbiphenyl5a 9l (Table 3, entry 12). The general procedure afforded 63% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.00 (s, 6H), 3.68 (s, 3H), 6.93e7.39 (m, 7H). 4.8.13. 4-Acetylbiphenyl5a 9m (Table 3, entry 13). The general procedure afforded 98% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.65 (s, 3H), 7.40e7.50 (m, 3H), 7.62 (d, J¼7.5 Hz, 2H), 7.69 (d, J¼7.8 Hz, 2H), 8.04 (d, J¼7.8 Hz, 2H). 4.8.14. 2-Methylbiphenyl13 9n (Table 4, entry 1). The general procedure afforded 95% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.47 (s, 3H), 7.42e7.46 (m, 4H), 7.51e7.59 (m, 5H). 4.8.15. 3-Methylbiphenyl13 9o (Table 4, entry 2). The general procedure afforded 99% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.58 (s, 3H), 7.33 (d, J¼7.2 Hz, 1H), 7.46e7.61 (m, 6H), 7.75 (d, J¼7.5 Hz, 2H). 4.8.16. 4-Methylbiphenyl13 9p (Table 4, entry 3). The general procedure afforded 94% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.53 (s, 3H), 7.37e7.58 (m, 5H), 7.64 (d, J¼8.1 Hz, 2H), 7.73 (d, J¼7.5 Hz, 2H). 4.8.17. 4-Methoxy-20 -methylbiphenyl14 9q (Table 4, entry 4). The general procedure afforded 98% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.43 (s, 3H), 3.96 (s, 3H), 7.08e7.11 (m, 2H), 7.38e7.42 (m, 6H). 4.8.18. 2-Methoxyl-20 -methylbiphenyl5a 9r (Table 4, entry 5). The general procedure afforded 96% of the title compound. The 1H NMR is same as those of compound 9h. 4.9. General method for the SuzukieMiyaura reaction of heteroaryl halides or heteroaryl boronic acids In a dry schlenk tube with a magnetic bar, 6a (40 mg, 6 mol %), Pd(OAc)2 (5.4 mg, 3 mol %), and K3PO4 (594 mg, 2.8 mmol) in 5 mL of THF/H2O (5:1) were placed under argon. Heteroaryl halide (0.8 mmol) was added via syringe and followed by adding phenylboronic acid (1.2 mmol). The resulting mixture was stirred at reflux for 12 h. The solvent was evaporated in vacuo and the residue was purified by flash column

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chromatography (petroleum ether/EtOAc¼100:1) to give the desired product.

300 MHz, TMS) d 2.25 (s, 3H), 7.18e7.33 (m, 5H), 7.62 (d, J¼7.8 Hz, 1H), 8.57e8.58 (m, 2H).

4.9.1. 3-(4-Methoxylphenyl)thiophene15 10a (Table 5, entry 1). The general procedure afforded 92% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.82 (s, 3H), 6.92 (d, J¼8.7 Hz, 2H), 7.33e7.35 (m, 3H), 7.52 (d, J¼8.7 Hz, 2H).

4.9.14. 3-Fluoro-2-phenylpyridine 10n (Table 5, entry 14). The general procedure afforded 97% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 7.23e7.29 (m, 1H), 7.43e7.51 (m, 4H), 7.95e7.97 (m, 2H), 8.51e8.53 (m, 1H).

4.9.2. 3-(2-Methoxylphenyl)thiophene16 10b (Table 5, entry 2). The general procedure afforded 95% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.76 (s, 3H), 6.88e6.92 (m, 2H), 7.18e7.27 (m, 2H), 7.39e7.45 (m, 2H), 7.55 (s, 1H).

4.9.15. 2-Phenylthiophene13 10o (Table 5, entry 15). The general procedure afforded 88% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 7.06e7.62 (m, 8H).

15

4.9.3. 3-(2-Methylphenyl)thiophene 10c (Table 5, entry 3). The general procedure afforded 85% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.33 (s, 3H), 7.13e7.34 (m, 7H). 4.9.4. 1-(4-(Thiophen-3-yl)phenyl)ethanone15 10d (Table 5, entry 4). The general procedure afforded 94% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.62 (s, 3H), 7.43 (m, 2H), 7.57 (s, 1H), 7.69 (d, J¼8.4 Hz, 2H), 7.99 (d, J¼8.4 Hz, 2H). 4.9.5. 3-p-Tolylthiophene18 10e (Table 5, entry 5). The general procedure afforded 95% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.36 (s, 3H), 7.20 (d, J¼7.8 Hz, 2H), 7.36e7.39 (m, 3H), 7.48 (d, J¼7.8 Hz, 2H). 4.9.6. 3-(Thiophen-3-yl)pyridine19 10f (Table 5, entry 6). The general procedure afforded 87% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 7.11e7.14 (m, 1H), 7.29e7.38 (m, 3H), 7.87 (d, J¼7.5 Hz, 1H), 8.52 (m, 1H), 8.89 (m, 1H). 20

4.9.7. 5-Methyl-2,30 -bithiophene 10g (Table 5, entry 7). The general procedure afforded 90% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.53 (s, 3H), 6.72 (s, 1H), 7.02 (m, 1H), 7.30e7.42 (m, 3H).

4.9.16. 2-(2-Methoxyphenyl)thiophene21 10p (Table 5, entry 16). The general procedure afforded 86% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.75 (s, 3H), 6.80e6.91 (m, 2H), 6.94e6.99 (m, 1H), 7.18e7.21 (m, 2H), 7.36e7.40 (m, 1H), 7.48e7.53 (m, 1H). 4.9.17. 2-(Biphenyl-4-yl)-5-ethylpyrimidine22 10q (Table 5, entry 17). The general procedure afforded 92% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 1.31 (t, J¼7.5 Hz, 3H), 2.68 (q, J¼7.5 Hz, 2H), 7.36e7.48 (m, 3H), 7.67 (d, J¼6.9 Hz, 2H), 7.72 (d, J¼8.4 Hz, 2H), 8.50 (d, J¼8.4 Hz, 2H), 8.65 (s, 2H). 4.9.18. 1,2-Bis(2-methyl-5-phenylthiophen-3-yl)cyclopent-1-ene 10r (Table 5, entry 18). The general procedure afforded 43% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 1.94 (s, 6H), 2.08 (m, 2H), 2.84 (d, J¼7.6 Hz, 4H), 7.03 (s, 2H), 7.19e7.25 (m, 2H), 7.30e7.35 (m, 4H), 7.50 (d, J¼7.8 Hz, 2H). 4.10. General method for the SuzukieMiyaura reaction with low catalyst loading

4.9.8. 3-(2-Methoxyphenyl)pyridine15 10h (Table 5, entry 8). The general procedure afforded 89% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.75 (s, 3H), 6.94e7.02 (m, 2H), 7.24e7.35 (m, 3H), 7.81 (d, J¼7.5 Hz, 1H), 8.51 (d, J¼3.3 Hz, 1H), 8.77 (s, 1H).

In a schlenk tube with a magnetic bar, aryl chloride (0.8 mmol), arylboronic acid (1.2 mmol), K3PO4 (594 mg, 2.8 mmol), and 5 mL of THF/H2O (5:1) were placed under argon. The amount of the palladium catalyst was added as indicated in Table 6. The resulting mixture was stirred at reflux for 12 h. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (petroleum ether/EtOAc¼100:1) to give the desired product.

4.9.9. 3-(Thiophen-2-yl)pyridine17 10i (Table 5, entry 9). The general procedure afforded 82% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 7.30e7.53 (m, 4H), 7.86 (d, J¼7.5 Hz, 2H), 8.54 (m, 1H), 8.88 (m, 1H).

4.10.1. 2-Methoxyl-40 -tert-butyl-biphenyl18 11b (Table 6, entry 2). The general procedure afforded 94% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 1.35 (s, 9H), 3.80 (s, 3H), 6.96e7.03 (m, 2H), 7.26e7.33 (m, 2H), 7.41e7.49 (m, 4H).

4.9.10. 3,30 -Bipyridine17 10j (Table 5, entry 10). The general procedure afforded 85% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 7.40e7.44 (dd, J¼6.4 Hz, 5.1 Hz, 1H), 7.89 (d, J¼6.4 Hz, 1H), 7.66 (d, J¼5.1 Hz, 1H), 8.85 (s, 1H).

4.10.2. 2-Methoxyl-40 -methylbiphenyl23 11c (Table 6, entry 3). The general procedure afforded 98% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.44 (s, 3H), 3.85 (s, 3H), 7.01e7.08 (m, 2H), 7.27e7.39 (m, 4H), 7.47e7.50 (m, 2H).

4.9.11. 2-(4-Methoxyphenyl)benzofuran15 10k (Table 5, entry 11). The general procedure afforded 85% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.86 (s, 3H), 6.88 (s, 1H), 6.97 (d, J¼8.1 Hz, 2H), 7.23e7.29 (m, 2H), 7.8e7.54 9 (m, 2H), 7.80 (d, J¼8.1 Hz, 2H).

4.10.3. 2-Methoxyl-20 -methylbiphenyl5a 11d (Table 6, entry 4). The general procedure afforded 96% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.34 (s, 3H), 3.91 (s, 3H), 7.11e7.20 (m, 2H), 7.32e7.52 (m, 6H).

4.9.12. 3-(2-Methoxylphenyl)thiophene15 10l (Table 5, entry 12). The general procedure afforded 95% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.76 (s, 3H), 6.88e6.92 (m, 2H), 7.18e7.27 (m, 2H), 7.39e7.45 (m, 2H), 7.55 (s, 1H). 14

4.9.13. 3-o-Tolylpyridine 10m (Table 5, entry 13). The general procedure afforded 82% of the title compound. 1H NMR (CDCl3,

4.10.4. 2-Methoxyl-20 -trifluoromethylbiphenyl24 11e (Table 6, entry 5). The general procedure afforded 69% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.75 (s, 3H), 6.80e6.87 (m, 3H), 7.17e7.28 (m, 2H), 7.36e7.50 (m, 2H), 7.66 (d, J¼7.8 Hz, 1H). 4.10.5. 2-Methoxyl-30 -trifluoromethylbiphenyl15 11f (Table 6, entry 6). The general procedure afforded 99% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 3.86 (s, 3H), 6.93 (d, J¼8.1 Hz, 1H),

T. Liu et al. / Tetrahedron 68 (2012) 6535e6547

7.10 (s, 1H), 7.16 (d, J¼7.5 Hz, 1H), 7.37 (t, J¼7.8 Hz, 1H), 7.50e7.60 (m, 2H), 7.73 (d, J¼7.8 Hz, 1H), 7.82 (m, 1H). 4.10.6. 3-Phenylpyridine15 11g (Table 6, entry 7). The general procedure afforded 76% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 7.33e7.59 (m, 6H), 7.86 (d, J¼7.8 Hz, 1H), 6.58 (d, J¼3.6 Hz, 1H), 8.85 (s, 1H). 4.10.7. 4-Acetyl-30 -trifluoromethylbiphenyl25 11h (Table 6, entry 8). The general procedure afforded 98% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.51 (s, 3H), 7.45e7.56 (m, 4H), 7.65 (d, J¼7.2 Hz, 1H), 7.73 (s, 1H), 7.92 (d, J¼8.4 Hz, 2H).

2. 3.

4. 5.

6.

4.10.8. 4-Acetylbiphenyl5a 11i (Table 6, entry 9). The general procedure afforded 98% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.65 (s, 3H), 7.40e7.50 (m, 3H), 7.62 (d, J¼7.5 Hz, 2H), 7.69 (d, J¼7.8 Hz, 2H), 8.04 (d, J¼7.8 Hz, 2H).

7.

4.10.9. 4-Chlorobiphenyl26 11j (Table 6, entry 10). The general procedure afforded 84% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 7.24e7.55 (m, 9H). 4.10.10. 4-Chlorobiphenyl5a 11k (Table 6, entry 11). The general procedure afforded 84% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 7.24e7.55 (m, 9H). 4.10.11. Biphenyl-2-carbonitrile25 11l (Table 6, entry 12). The general procedure afforded 63% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 7.21e7.32 (m, 2H), 7.35e7.50 (m, 5H), 7.56e7.59 (m, 2H). 0

8.

9.

14

4.10.12. 4-Methoxy-4 -methylbiphenyl 11m (Table 6, entry 13). The general procedure afforded 98% of the title compound. 1H NMR (CDCl3, 300 MHz, TMS) d 2.38 (s, 3H), 3.84 (s, 3H), 6.95 (d, J¼8.2 Hz, 2H), 7.22 (d, J¼7.8 Hz, 2H), 7.44 (d, J¼7.8 Hz, 2H), 7.50 (d, J¼8.2 Hz, 2H).

10. 11.

Acknowledgements The authors gratefully acknowledge the financial support from National Basic Research Program of China (2010CB126103), Special Fund for Agro-scientific Research in the Public Interest (201103007), the National Key Technologies R&D Program (2011BAE06B05), Shanghai Scientific Research Program (10XD1405200), the Key Program of National Natural Science Foundation of China (21032006), National Natural Science Foundation of China (21172245/B020304/21172248), for financial support.

12. 13. 14. 15. 16.

Supplementary data

17. 18. 19.

Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.tet.2012.05.068.

20. 21. 22.

References and notes

23. 24. 25. 26.

1. (a) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 36, 3437; (b) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 15, 2419; (c) Miyaura, N., Chapter

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2 In Metal-catalyzed Cross-coupling Reaction; Diederich, F., de Meijere, A., Eds.; Wiley-VCH: New York, NY, 2004; (d) Miyaura, N. Top. Curr. Chem. 2002, 219, 11; (e) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176. (a) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461; (b) Altman, R. A.; Buchwald, S. L. Nature Protocols 2007, 2, 3115. (a) Netherton, M. R.; Dai, C.; Neuschuta, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 10099; (b) Kirchoff, J. H.; Netherton, M. R.; Hills, I. D.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 13662. (a) Herrmann, W. A.; Reisinger, C. P.; Spiegler, M. J. Organomet. Chem. 1998, 557, 93; (b) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290. (a) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101; (b) Navarro, O.; Marion, N.; Mei, J.; Nolan, S. P. Chem.dEur. J. 2006, 12, 5142; (c) Organ, M. G.; Alimsiz, S. C.; Sayah, M.; Hoi, K. H.; Lough, A. J. Angew. Chem., Int. Ed. 2009, 48, 2383; (d) Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F. J. Am. Chem. Soc. 2004, 126, 15195. (a) Zapf, A.; Ehrentraut, A.; Beller, M. Angew. Chem., Int. Ed. 2000, 39, 4153; (b) Zapf, A.; Jackstell, R.; Rataboul, F.; Riermeier, T.; Monsees, A.; Fuhrmann, C.; Shaikh, N.; Dingerdissen, U.; Beller, M. Chem. Commun. 2004, 38. (a) Fihri, A.; Luart, D.; Len, C.; Solhy, A.; Chevrinb, C. P. V. Dalton Trans. 2011, 40, 3116; (b) Hierso, J.-C.; Fihri, A.; Amardeil, R.; Meunier, P.; Doucet, H.; Santelli, M. Tetrahedron 2005, 61, 9759; (c) Scivanti, A.; Beghetto, V.; Matteoli, U.; Antonaroli, S.; Marini, A.; Crociani, B. Tetrahedron 2005, 61, 9752; (d) Dai, W.M.; Li, Y.; Zhang, Y.; Lai, K. W.; Wu, J. Tetrahedron Lett. 2004, 45, 1999; (e) Joshaghani, M.; Daryanavard, M.; Rafiee, E.; Xiao, J.; Collin Baillie, C. Tetrahedron Lett. 2007, 48, 2025; (f) Arvela, R.; Leadbeater, N. E.; Mack, T. L.; Kormos, C. M. Tetrahedron Lett. 2006, 47, 217; (g) Jiang, N.; Ragauskas, A. J. Tetrahedron Lett. 2006, 47, 197; (h) Lee, D.-H.; Jin, M.-J. Org. Lett. 2011, 13, 252; (i) Hierso, J.rin, M.; Meunier, P. Eur. J. Inorg. Chem. 2007, 3767; (j) Diebolt, O.; C.; Beaupe Braunstein, P.; Nolan, S. P.; Cazin, C. S. J. Chem. Commun. 2008, 3190; (k) Baillie, C.; Zhang, L.; Xiao, J. J. Org. Chem. 2004, 69, 7779; (l) Kwong, F. Y.; Lam, W. H.; Yeung, C. H.; Chan, K. S.; Chan, A. S. C. Chem. Commun. 2004, 1922; (m) Sprengers, J. W.; Wassenaar, J.; Clement, N. D.; Cavell, K. G.; Elsevier, C. J. mez Andreu, M.; Angew. Chem., Int. Ed. 2005, 44, 2026; (n) Jackstell, R.; Go €ttger, D.; Frisch, A.; Selvakumar, K.; Zapf, A.; Klein, H.; Spannenberg, A.; Ro Briel, O.; Karch, R.; Beller, M. Angew. Chem., Int. Ed. 2002, 41, 986. (a) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem., Int. Ed. 2007, 46, 2768; (b) Valente, C.; C¸alimsiz, S.; Hoi, K. H.; Mallik, D.; Sayah, M.; Organ, M. G. Angew. Chem., Int. Ed. 2012, 51, 3314. (a) Arduengo, A. J., III; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991, 113, 361; (b) Arduengo, A. J., III. Acc. Chem. Res. 1999, 32, 913; (c) Bourissou, D.; Guerret, O.; Gabba, F. P.; Bertrand, G. Chem. Rev. 2000, 100, 39; (d) Herrmann, W. A.; Kacher, C. Angew. Chem., Int. Ed. 1997, 36, 2162. (a) Joule, J. A.; Mills, K. Heterocyclic Chemistry; Blackwell Science: Malden, MA, 2000; (b) Tyrell, E.; Brookes, P. Synthesis 2004, 4, 469. (a) Billingsley, K. L.; Anderson, K. W.; Buchwald, S. L. Angew. Chem., Int. Ed. 2006, 45, 3484; (b) Billingsley, K.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 3358; (c) Barder, T. E.; Buchwald, S. L. Org. Lett. 2004, 6, 2649; (d) Kondolff, I.; Doucet, H.; Santelli, M. Synlett 2005, 2057; (e) Thompson, A. E.; Hughes, G.; Batsanov, A. S.; Bryce, M. R.; Parry, P. R.; Tarbit, B. J. Org. Chem. 2005, 70, 388; (f) Kudo, N.; Pereghini, M.; Fu, G. C. Angew. Chem., Int. Ed. 2006, 45, 1282; (g) Guram, A. S.; King, A. O.; Allen, J. G.; Wang, X.; Schenkel, L. B.; Chan, J.; Bunel, E. E.; Faul, M. M.; Larsen, R. D.; Martinelli, M. J.; Reider, P. J. Org. Lett. 2006, 8, 1787. Garret, C. E.; Prasad, K. Adv. Synth. Catal. 2004, 346, 889. Yamada, Y. M. A.; Watanabe, T.; Beppu, T.; Fukuyama, N. ,; Torri, K.; Uozumi, Y. Chem.dEur. J. 2010, 16, 11311. Ackermann, L.; Althammer, A. Org. Lett. 2006, 8, 3457. Kondolff, I.; Doucet, H.; Santelli, M. J. Heterocycl. Chem. 2008, 45, 109. Chaignon, N. M.; Fairlamb, I. J. S.; Kapdi, A. R.; Taylor, R. J. K.; Whitwood, A. C. J. Mol. Catal. A 2004, 219, 191. Fleckenstein, C. A.; Plenio, H. Chem.dEur. J. 2008, 14, 4267. Andrus, M. B.; Song, C. Org. Lett. 2001, 3, 3761. Lee, D.-H.; Choi, M.; Yu, B.-W.; Ryoo, R.; Taher, A.; Hossain, S.; Jin, M.-J. Adv. Synth. Catal. 2009, 351, 2912. Saini, G.; Lucas, N. T.; Jacob, J. Tetrahedron Lett. 2010, 51, 2956. Pena, M. A.; Sestelo, J. P.; Sarandeses, L. A. J. Org. Chem. 2007, 72, 1271. de Jong, J. J. D.; Lucas, L. N.; Hania, R.; Pugzlys, A.; Kellogg, R. M.; Feringa, B. L.; Duppen, K.; van Esch, J. H. Eur. J. Org. Chem. 2003, 10, 1887. Sreedhar, B.; Yada, D.; Reddy, P. S. Adv. Synth. Catal. 2011, 343, 2823. Lourak, M.; Vanderesse, R.; Fort, Y.; Caubere, P. J. Org. Chem. 1989, 54, 4844. Han, X.; Weng, Z.; Hor, T. S. A. J. Organomet. Chem. 2007, 692, 5690. Mao, J.; Guo, J.; Fang, F.; Ji, S.-J. Tetrahedron 2008, 64, 3905.