Palladium-carbene catalyzed direct arylation of five-membered heteroaromatics

CRediT author statement

Murat Kaloğlu and Nazan Kaloğlu: Conceptualization, Methodology, Investigation, Writing-Original Draft,

Writing-Review & Editing.

İlkay Yıldırım and Namık Özdemir: Software, Writing-Original Draft, Investigation.

İsmail Özdemir: Conceptualization, Resourches, Writing-Original Draft, Supervision, Funding Acquisition.

Palladium-Carbene Catalyzed Direct Arylation of Five-Membered

Heteroaromatics

[a,b]

[c]

[d]

[a,b]

Murat Kaloğlu, Nazan Kaloğlu, İlkay Yıldırım, Namık Özdemir and İsmail Özdemir*

a

İnönü University, Faculty of Science and Arts, Department of Chemistry, 44280 Malatya, Turkey

İnönü University, Catalysis Research and Application Center, 44280 Malatya, Turkey

Biruni University, Vocational School of Health Services, Department of Radiotherapy, 34010 İstanbul, Turkey

Ondokuz Mayıs University, Faculty of Education Department of Mathematics and Science Education, 55139 Samsun, Turkey

b

c

d

ABSTRACT: Due to the industrial importance of bi(hetero)arenes, the synthesis of these compounds by

homogeneous Pd-catalyzed direct arylation is an important research topic in modern organic chemistry. In this study,

PEPPSI-type, (PEPPSI = Pyridine Enhanced Precatalyst Preparation Stabilization and Initiation), new Pd-catalysts

with N-heterocyclic carbene ligand were synthesized, and they were used as catalysts in the synthesis of

bi(hetero)arenes by direct arylation process. The structures of Pd-carbene complexes were elucidated by different

spectroscopic and analytical techniques such as NMR, FT-IR and elemental analysis. The more detailed structural

characterization of one of the complexes was determined by single-crystal X-ray diffraction study. Pd-carbene

complexes were used as effective catalysts in the direct arylation of five-membered heteroaromatics such as thiophene,

furan and thiazole derivatives with (hetero)aryl bromides for 1 h, in the presence of 1 mol% of catalyst loading, and

successful results were obtained.

Keywords: N-Heterocyclic carbene, palladium, PEPPSI, direct arylation, heteroaromatics.

*

Corresponding author:

Tel and Fax: +904223410212

E-mail address: ismail.ozdemir@inonu.edu.tr

https://www.inonu.edu.tr/

1

. Introduction

Bi(hetero)arenes are known as important units in the design of advanced materials, natural products, agrochemicals,

1-6

pharmaceuticals and cosmetics. Because of their applications in industrial area, the preparation of bi(hetero)arenes is

an important research area in modern synthetic organic chemistry. To date, a number of strategies have been developed

for the preparation of bi(hetero)arenes. The most common ones of among these strategies are, of course, the traditional

7

8

9

10

cross-coupling reactions catalyzed by transition-metal (TM) catalysts. Suzuki, Stille, Negishi or Kumada type

reactions are widely used in the TM-catalyzed synthesis of bi(hetero)arenes. However, the organometallic compounds

used in such reactions are generally non-commercially available, or relatively expensive chemicals. In these reactions,

the starting coupling partners should bear either a metal-containing functionality or a halogen atom and related groups.

In this case in fact the preliminary preparation of two independent, expensive, starting materials is required. These

processes have also some disadvantages such as generating stoichiometric amounts of waste materials and the use of

unstable and corrosive chemicals etc. Therefore, there is a need for more environmentally attractive and atom

economical methods in which total synthesis steps and by-product formation are minimized.

The direct arylation of bi(hetero)arenes by C-H bond activation provides an ideal alternative to traditional cross-

coupling reactions in the synthesis of bi(hetero)arenes. This methodology is environmentally attractive, as the major

reaction by-product is HX associated to a base, instead of the metallic salts mixture which is produced under the more

1

1,12

classical Suzuki, Negishi or Stille cross-coupling reactions.

In this process, a variety of arylating reagents including

13

14

15

16

aryl halides, aryl organometallic reagents, unactivated simple arenes, and phenol derivatives such as triflates,

17

18

mesylates and arene sulfonyl chlorides have been employed. Particularly, aryl halides are the electrophilic reagents

which are the most popular among the arylating reagents, due to their commercial availability and the variety of

substrates. The Pd-catalyzed direct arylation of (hetero)arenes was firstly reported by Nakamura, Tajima and Sakai in

19

20

1

982, and by Ohta in 1985. Since then, the Pd-catalyzed direct arylation of (hetero)arenes with aryl halides has

proved to be a powerful method for the synthesis of a wide variety of arylated heteroaromatics. To date, Pd-catalyzed

21

22

23

direct arylation of (hetero)arenes, especially five-membered heterocycles such as thiophene, furan and thiazole

has been largely described by a large number of researchers.

N-Heterocyclic carbenes (NHCs) are effective ligands that allow the preparation of the most suitable steric,

24

electronic and chemically acceptable catalyst by altering the substituents on the nitrogen atom. Due to these features,

25

they have been successfully employed in different applications of organometallic chemistry , and they are a key

ligand for metal complexes, because of their wide applicability in catalysis. Thanks to the strong σ-donor and weak π-

acceptor property, NHCs do not dissociate easily from the metal center by interacting strongly with the coordinated

metal. Due to activity, stability and selectivity of metal complexes containing NHC ligand, they have been widely used

26

as highly reactive and rather selective catalysts for numerous reactions. Recently, different-type of Pd-NHC

2

7a

27b

27c

27d

complexes have been prepared by Caddick and Cloke, Bellemin-Laponnaz and Gade, Nolan, Herrmann, and

27e

Organ, (Figure 1). These different-type Pd-NHC complexes showed high levels of activity in a variety of cross-

28

coupling reactions.

Figure 1. Examples of Pd-NHC species commonly used in cross-coupling reactions.

27e

After the discovery of Organ's PEPPSI-type Pd-complexes in 2006, (PEPPSI = Pyridine Enhanced Precatalyst

Preparation Stabilization and Initiation), these type complexes have shown remarkable catalytic activities towards

29

various carbon-carbon and carbon-heteroatom cross-coupling reactions. PEPPSI-type Pd-NHC complexes represent a

class of Pd-NHC catalysts completely different from other Pd-NHC complexes. Unlike other types of Pd-NHC

30

complexes, PEPPSI-type Pd-NHC complexes are easier to synthesize and use. The high activity of PEPPSI-type Pd-

complexes in catalysis has been based on to the presence of a loosely bound throw-away pyridine ligand that makes

31

way for the incoming substrate. In recent years, PEPPSI-type Pd-complexes have been used as effective catalysts in

32

the direct arylation and successful results have been obtained. In this context, recently we have also synthesized and

characterized benzimidazole-based new PEPPSI-type Pd-NHC complexes, and have investigated catalytic activity of

33

these complexes in the direct arylation reactions. In view of the above information and the growing interest in

catalytic activity of Pd-carbene complexes to act as an efficient catalyst in the direct arylation, in this article, we now

report the preparation of PEPPSI-type five new Pd-NHC complexes (2a-2e) of the general formula

[

PdX (NHC)(pyridine)], (X = Cl, Br; NHC = 1,3-disubstituted benzimidazole-2-ylidene), and their characterization by

2

1

13

different techniques such as H NMR, C NMR, FT-IR, and elemental analysis. The solid-state structure of one of the

Pd-complexes {trans-dibromo-[1-(4-methylbenzyl)-3-(3-methoxylbenzyl)benzimidazole-2-ylidene]-(pyridine)-

palladium(II)}, (2c) was established by single-crystal X-ray diffraction study. In the present study, the catalytic

application of 2a-2e Pd-carbene complexes have been tested in the direct arylation of five-membered heteroaromatics

such as thiopene, furan and thiazole with (hetero)aryl bromides in presence of 1 mol% catalyst loading.

2

. Results and discussion

2

.1. Synthesis

34

35

36

37

1

a, 1b, 1c and 1e benzimidazolium salts as NHC ligand precursors were synthesized as previously described in

the literature. The general procedure for the benzimidazolium salts (1a-1e) and their corresponding PEPPSI-type Pd-

NHC complexes (2a-2e) are shown in the Scheme 1. Also, some physical and spectroscopic data of all new

compounds are summarized in Table 1.

Scheme 1. Synthesis of the benzimidazolium salts (1a-1e) and their PEPPSI-type palladium-NHC complexes (2a-2e).

Table 1. Physical and spectroscopic properties of new compounds.

o

-1

1

13

Compound

Molecular formula

Isolated yield (%)

M.p. ( C)

v

(CN) (cm )

H(2) H NMR (ppm)

C(2) C NMR (ppm)

1

2

d

a

b

c

C

25

23

28

30

31

H

27BrN

25Br

35Cl

2

O

90

78

71

83

75

80

199-200

202-203

196-197

222-223

247-248

213-214

1553

1403

1409

1395

1405

11.74

─

144.2

164.3

163.0

164.2

164.0

163.9

2

N

3

Pd

2

N

3

Pd

─

27Br

31Br

33Br

2

N

3

OPd

─

d

e

3

─

2

.2. Preparation of benzimidazolium salts

The benzimidazolium salts (1a-1e) were synthesized by the reaction of different N-(benzyl)-benzimidazoles with 3-

o

methoxybenzyl chloride or n-butyl chloride in dimethylformamide (DMF) at 80 C for 36 h (Scheme 1). The new 1d

benzimidazolium salt was characterized by different techniques. As shown in Table 1, the FT-IR data clearly indicated

-

1

that the 1d benzimidazolium salt exhibit a characteristic ν₍_C_N₎band typically at 1553 cm . In the H NMR spectra,

13

C(2)-H proton resonance was observed at δ = 11.74 ppm as sharp singlets. In the C NMR spectra, C(2)-carbon

resonance was observed at δ = 144.2 ppm as single signal. These downfield signals of the acidic C(2)-H proton and

C(2)-carbon were support the formation of 1d benzimidazolium salt. These spectroscopic data of 1d benzimidazolium

22f,33-37

salt are consistent with the data observed for other benzimidazolium salts in the literature.

2

.3. Preparation of PEPPSI-type palladium–NHC complexes

28

The PEPPSI-type Pd-NHC complexes (2a-2e) were synthesized in a similar manner to that reported by Organ . The

general procedure for the preparation of complexes is shown in Scheme 1. Five new Pd-carbene complexes were

synthesized by reaction of the corresponding benzimidazolium salts (1a-1e) with PdCl in the presence of pyridine. All

2

Pd-carbene complexes were isolated as air-stable, yellow solids, and they were soluble in solvents such as

dichloromethane, chloroform, toluene, and tetrahydrofuran and insoluble in non-polar solvents. All new Pd-carbene

1

13

complexes were characterized by different techniques. In the H NMR and C NMR spectra of the Pd-carbene

complexes, the absence of the characteristic signals of the acidic C(2)-H proton and C(2)-carbon of the

benzimidazolium salts, suggests the formation of Pd-carbene bond. Also, the characteristic signals of aromatic

1

hydrogens of pyridine ring were observed as downfield resonances in the H NMR spectra between δ = 7.34-9.03 ppm.

These signals suggest that the pyridine ring coordinated to the palladium centre to form a PEPPSI-type palladium

13

complex. In the C NMR spectra, the characteristic C(2)-carbene signals of 2a-2e complexes are appear as singlet at δ

164.3, 163.0, 164.2, 164.0, 163.9 ppm, respectively. Also, characteristic signals of the aromatic carbons of

=

pyridine ring at approximately δ = 124, 137 and 152 ppm, support the formation of PEPPSI-type palladium

complex. The NMR spectra also provide a potential tool to estimate the electronic properties of these Pd-carbene

13

complexes. In the C NMR spectra, due to the 2,4,6-trimethylbenzyl and 2,3,5,6-tetramethyl benzyl groups increasing

the electron density of the NHC ring, the Pd-carbene signals of the complex 2c (δ = 164.2 ppm) are shifted further

downfield as compared to those of complexes 2d and 2e. This observation is in agreement with the downfield-shifted

13

Pd-carbene signal of the complex 2a (δ = 164.3 ppm) in comparison to that of complex 2b in the C NMR spectra.

The FT-IR data clearly indicated that the PEPPSI-type Pd-NHC complexes exhibit a characteristic ν band typically

(

CN)

-

1

between 1395-1409 cm . The FT-IR spectra of all five Pd-complexes show similar absorption bands with

-1

moderately shifted wavelengths (mostly less than 15 cm ). Due to the flow of electrons from the carbene ligand to

the palladium centre, the C=N bond is weakened, and as a result, a decreasing in the v₍_C_N₎stretching frequency is

observed. Therefore, in comparison to the 1a-1e ligand precursors, 2a-2e Pd-complexes give rise to obvious red-

shifted absorption bands. These complexes show typical spectroscopic signatures, which are in line with those

33

reported for other similar type Pd-complexes. Also, additional elemental analysis results of these complexes are in

agreement with the proposed molecular formula.

2

.4. Description of the crystal structure

The complex consists of a 1-(3-methoxybenzyl)-3-(4-methylbenzyl)-2,3-dihydro-1H-benzo[d]imidazole ligand with a

II

Pd metal center and two bromide ligands. The metal coordination environment features a square-planar geometry, in

which the NHC and the pyridine are trans to each other. This reflects the tendency to avoid a sterically more crowded

cis-configuration. The cis- angles varying from 87.51(17) to 92.60(16)° and the trans- angles changing from 175.82(3)

to 178.1(2)° are a little off from the ideal values of 90 and 180°. The four-coordinate geometry index for the complex,

38

τ , is 0.04. In the case of an ideal square-planar geometry, the τ value is equal to zero, while it becomes unity for a

4

perfect tetrahedral geometry. Consequently, the value of τ shows that the coordination polyhedron of the palladium

4

atom is a slightly distorted square-planar. In the square-planar environment, the Pd atom is lying 0.0210(5) Å out the

coordination plane defined by atoms Br1, Br2, N3 and C1.

The Pd─C_c_a_r_b_e_n_ebond distance [1.967(5) Å] is slightly smaller than the sum of the individual covalent radii of the

palladium and carbon atoms (2.12 Å), while the Pd─N_p_y_r_i_d_i_n_ebond distance [2.110(5) Å] is almost equal to the sum of

39

the covalent individual radii of the palladium and nitrogen atoms (2.10 Å). The internal N─C─N ring angle at the

carbene center is 108.2(5)°. Furthermore, the Pd─Br1 and Pd─Br2 bonds only differ by ca. 0.01 Å, and interestingly

bent toward NHC ligand rather than toward the nonbulky pyridine ligand. These values are in good agreement with

33,40

those found in other Pd-NHC-Pyridine complexes.

The carbene ring is oriented almost perpendicularly to the

PdCNBr coordination plane with a dihedral angle of 81.28(19)°, which is typical for NHC complexes to relieve steric

2

congestion. On the other hand, the pyridine ring is inclined at an angle of 48.8(3)° with the coordination plane. Finally,

the NHC ring makes dihedral angles of 88.8(3) and 82.2(3)° with the methoxybenzene and methylbenzene rings,

respectively.

The molecular structure of 2c complex with the atom-labelling scheme is shown in Figure 3, while relevant bond

distances and angles are reported in Table 2.

Figure 3. The molecule of 2c, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 20%

probability level. For clarity purpose, hydrogens have been omitted and only the major part of disordered fragment is

drawn.

Table 2. Selected geometric parameters for complex 2c.

Bond lengths (Å)

Pd1─C1

Pd1─N3

Pd1─Br1

Pd1─Br2

N1─C1

1.967(5)

2.110(5)

2.4189(9)

2.4293(9)

1.332(7)

N1─C2

N1─C8

N2─C1

N2─C7

N2─C16

1.391(7)

1.470(7)

1.339(6)

1.389(7)

1.463(6)

Bond angles (°)

C1─Pd1─N3

C1─Pd1─Br1

N3─Pd1─Br1

C1─Pd1─Br2

N3─Pd1─Br2

Br1─Pd1─Br2

N1─C1─N2

178.1(2)

C1─N1─C2

C1─N1─C8

C2─N1─C8

C1─N2─C7

C1─N2─C16

C7─N2─C16

109.9(4)

126.3(5)

123.7(5)

109.5(4)

125.6(5)

124.9(4)

87.51(17)

91.39(16)

88.47(17)

92.60(16)

175.82(3)

108.2(5)

2

.5. Optimization of the reaction conditions for the direct arylation of heteroaromatics

Our first objective was to determine the most suitable reaction conditions. For this purpose, we first selected the

complex 2e as the model catalyst, 2-acetylthiophene, 2-furaldehyde and 4,5-dimethylthiazole as heteroaromatic

substrates and the p-bromobenzaldehyde as model coupling partner (Table 3). We selected DMAc as the solvent, and

KOAc as the base in this study, because the DMAc/KOAc combination has been commonly used for the direct

21-23

arylation of heteroarenes.

In literature, it is known to difficult to achieve high selectivity in such direct arylation

reactions without the use of stoichiometrically large amounts of heteroaromatic compound relative to amount of aryl

23j

halide. Since the 2-acetylthiophene and 2-furaldehyde have also other positions such as C3 and C4 to react with aryl

bromide, so 1 equivalent of p-bromobenzaldehyde was used as the limiting reagent to prevent di- or tri-arylation. Thus

mono-arylation of the heteroaromatic compound was targeted. Firstly, the C5-arylation of 2-acetylthiophene with p-

o

bromobenzaldehyde was carried out at 150 C for 10 h without the addition of Pd-catalyst in order to examine the

effect of catalyst on the reaction. As attempt, no products were formed without the addition of Pd-catalyst (Table 3,

entry 1). Under the same conditions, when only 1e NHC precursor was used as catalyst without any Pd-catalyst, no

reaction takes place (Table 3, entry 2). In the direct arylation reaction of 2-acetylthiophene with p-bromobenzaldehyde,

o

different Pd-salts such as Pd(OAc) and PdCl were tested using 1 mol% of catalyst loading at 150 C for 10 h.

2

Products were obtained in 45% and 28% yields with low conversions, respectively. When the reaction was carried out

for 18 h in the presence of the same Pd-salts, we observed that conversion and yield increased (Table 3, entries 3 and

4

5

9

). When in situ generated catalytic system with 1 mol% of 1e NHC precursor and 1 mol% of Pd(OAc) was used,

1% yield was observed (Table 3, entry 5). However, when the same conditions were used 2e Pd-complex as catalysts,

0% yield was observed with full conversion in the reaction. When the reaction time was increased to 18 h as in the

2

entries 3 and 4, we observed full conversion, but no significant difference in yield. (Table 3, entry 6). When the

reaction time was reduced from 10 h to 5 h, 87% yield was observed in the reaction (Table 3, entry 7). When the

reaction time was reduced from 5 h to 3 h or 3 h to 1 h at 150 °C, no noticeable effect on the yield was observed (Table

3

, entries 8,9). When the reaction temperature was reduced from 150 °C to 120 °C, no noticeable effect on the yield

was also observed (Table 3, entry 10), but when the reaction temperature was reduced from 120 °C to 90 °C, the yield

o

dropped to 27% (Table 3, entry 11). When the catalyst loading was decreased to 0.5 mol% at 120 C, yield was

observed to decrease significantly (Table 3, entry 12). As a result of the optimisation experiments in the arylation of 2-

acetylthiophene with p-bromobenzaldehyde, a very good yield (81%) with 96% conversion was obtained in

DMAc/KOAc combination in the presence of 1 mol% 2e Pd-catalyst at 120 °C for 1 h (Table 3, entry 10). For

coupling of 2-furaldehyde with p-bromobenzaldehyde, the same reaction condition was found to be optimal. In this

case a yield of 83% was observed with 97% conversion (Table 3, entry 13). When the arylation of 4,5-

dimethylthiazole with p-bromobenzaldehyde was tested at the same condition, only 50% coupling product was

o

obtained (Table 3, entry 14), so the temperature was increased up to 140 C and reaction yield was up to %78 with 91

conversion (Table 3, entry 15).

Table 3. Influence of the reaction conditions on the Pd� catalyzed direct arylation of five-membered heteroaromatics

a

with p-bromobenzaldehyde.

b

c

Entry

1

Heteroaromatics

[Pd] (mol%)

─

Time (h)

Temperature

Conversion (%)

─

56 (90)

45 (74)

60

100 (100)

100

99

97

96

46

42

97

72

91

Yield (%)

─

45 (76)

28 (61)

51

90 (91)

87

85

83

81

27

30

83

50

78

2-Acetylthiophene

2-Furaldehyde

10

5

3

1

150

120

90

d

2

3

4

5

e

Pd(OAc)

PdCl (1)

2

(1)

e

2

f

Pd(OAc)

2e (1)

2e (0.5)

2e (1)

2

e

6

7

8

9

1

0

1

2

3

4

5

1

120

140

4,5-Dimethylthiazole

a

b

c

d

e

f

Conditions: 2-acetylthiophene (2.0 mmol), p-bromobenzaldehyde (1.0 mmol), KOAc (1.5 mmol), DMAc (2 mL).

Conversions were calculated with respect to p-bromobenzaldehyde from the results of GC spectrometry with dodecane as internal standard.

GC yields.

Without any palladium catalyst, only 1e NHC precursor was used as catalyst.

Results obtained at 18 h are shown in parentheses.

2

In situ generated catalytic system with 1e NHC precursor and Pd(OAc) was used.

After successful results summarized in Table 3, we tried to evaluate the scope and limitations of the Pd-

complexes 2a-2e for the direct arylation of 2-acetylthiophene, 2� furaldehyde and 4,5-dimethylthiazole with different

hetero)aryl bromides. All reactions we performed for this purpose worked smoothly to give the desired arylated

(

products in moderate to high yields (see Table 4-6). Firstly, under the optimal condition, the direct arylation of 2-

acetylthiophene with various (hetero)aryl bromides were examined and the C(5)-arylated thiophene derivatives were

obtained with moderate to high yield. When 2-acetylthiophene was arylated with p-substituted aryl bromides and 3-

bromoquinoline, arylated products were obtained with 54-92% yields by using only 1 mol% Pd-complexes (2a-2e) as

2

1i

a catalyst (Table 4). The reaction of 2-acetylthiophene with bromobenzene generated the 5-phenyl-2-acetylthiophene

in 80% and 82% yield in the presence of 2d and 2e catalysts, respectively (Table 4, entries 4,5). The reaction of 2-

7c

acetylthiophene with p-bromobenzaldehyde gave the expected product in 81% yield in the presence of 2e catalyst

21g

(

Table 4, entry 9). Moderate to high yields of 5-(4-acetylphenyl)-2-acetylthiophene were obtained for the coupling

with p-bromoacetophenone (Table 4, entries 11-15). The reaction of 2-acetylthiophene with p-bromotoluene gave the

21h

expected product in 86% and 90% yield in the presence of 2d and 2e catalysts, respectively (Table 4, entries 19,20).

At among reaction arylated with bromobenzene, p-bromoanisole and p-bromotoluene using 1 mol% of catalyst, the

21g

reaction of the electron-rich p-bromoanisole with 2-acetylthiopene gave lower C5-arylated product (Table 4, entries

2

1-25). Pyridines are π-electron-deficient heterocycles. Therefore, their reactivity is quite similar to electron-deficient

33a

aryl bromides. As expected, using 3-bromoquinoline, we obtained the 3-(2-acetylthiophene-5-yl)quinoline

moderate to high yield (Table 4, entries 26-30).

in

a

Table 4. Palladium-catalyzed direct C(5)-arylation of 2-acetylthiophene with (hetero)aryl bromides.

b

Entry

Aryl bromide

[Pd]

Product

Yield (%)

78

76

68

80

82

73

69

64

71

81

62

59

72

75

80

83

79

68

86

90

66

54

64

70

68

69

81

75

86

92

1

2

3

4

5

6

7

8

9

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

1

2

0

1

2

3

4

5

6

7

8

9

0

1

2

3

4

5

6

7

8

9

0

3

a

Conditions: [Pd] 2a-2e (0.01 mmol), 2-acetylthiophene (2.0 mmol), aryl bromide (1.0 mmol), KOAc (1.5 mmol), DMAc (2 mL), 120 °C, 1 h.

GC yields were calculated with respect to aryl bromide from the results of GC spectrometry with dodecane as internal standard.

b

Using the same reaction conditions, we investigated the reactivity of 2-furaldehyde in Pd-catalyzed direct

arylation. As shown in Table 5, high yield C(5)-arylated products were obtained. Very close yields (65-84%) were

22a

observed for 2-furaldehyde using the neutral aryl bromide such as bromobenzene (Table 5, entries 1-5). The

coupling of 2-furaldehyde with electron-poor aryl bromide such as p-bromobenzaldehyde proceeds nicely. p-

22f

Bromobenzaldehyde gave the C(5)-arylated product with 65-83% yields (Table 5, entries 6-10). The electron-poor p-

bromoacetophenone was also a good substrate to afford the corresponding products 5-(4-acetylphenyl)-2-

22f

furaldehyde at between 61-79% yields (Table 5, entries 11-15). When the reaction of 2-furaldehyde with electron-

rich aryl bromides such as p-bromotoluene and p-bromoanisole was investigated, the yields were at between 75-80%

2

2a

for 4-bromotoluene with 2-furaldehyde

(Table 5, entries 16-20). p-Bromoanisole gave also the 5-(4-

2

2a

methoxyphenyl)-2-furaldehyde with 69-77% yields (Table 5, entries 21-25). 3-Bromoquinoline was found to be very

reactive in DMAc at 1 h (Table 5, entries 26-30). 3-(2-Furaldehyde-5-yl)quinoline was obtained in 87% yield in the

9b

presence of 2d catalysts (Table 5, entry 29).

a

Table 5. Palladium-catalyzed direct C(5)-arylation of 2-furaldehyde with (hetero)aryl bromides.

b

Entry

Aryl bromide

[Pd]

Product

Yield (%)

75

70

65

75

84

65

72

80

76

83

61

69

76

73

79

75

78

80

81

80

70

69

72

74

77

71

76

80

87

83

1

2

3

4

5

6

7

8

9

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

1

0

1

2

3

4

5

6

7

8

9

0

1

2

3

4

5

6

7

8

9

0

3

a

Conditions: [Pd] 2a-2e (0.01 mmol), 2-furaldehyde (2.0 mmol), aryl bromide (1.0 mmol), KOAc (1.5 mmol), DMAc (2 mL), 120 °C, 1 h.

GC yields were calculated with respect to aryl bromide from the results of GC spectrometry with dodecane as internal standard.

b

Finally, the scope of the direct arylation reaction was extended to 4,5-dimethylthiazole. The C2-position of 4,5-

dimethylthiazole was arylated because of blocked its C4- and C5-positions. We also found 4,5-dimethylthiazole to be a

suitable reactant for this reaction. In the direct arylation of 4,5-dimethylthiazole with p-substituted aryl bromides and

3

-bromoquinoline, a very high yield C(2)-arylated products were obtained at 140 °C for 1 h (Table 6). Best yields were

8c

obtained in the presence of 2d and 2e catalysts when bromobenzene was used (Table 6, entries 4,5). When p-

bromobenzaldehyde and p-bromoacetophenone were used, generally C(2)-arylated products were obtained in

moderate to high yield with all catalysts. (Table 6, entries 6-15). When p-bromotoluene was used, (4-methylphenyl)-

37

23g

4

,5-dimethylthiazole product was obtained in 84% yield in the presence of 2e catalyst (Table 6, entry 20). Moderate

23i

yields of 2-(4-methoxyphenyl)-4,5-dimethylthiazole were obtained for the coupling with p-bromoanisole (Table 6,

entries 21-25) with little variance between the Pd-complexes. We also tested the coupling with the 3-bromoquinoline.

23i

This heteroaryl bromide gave the expected 3-(4,5-dimethylthiazol-2-yl)quinoline in very good yields (Table 6,

entries 26-30). Generally, the reactivity of 4,5-dimethylthiazole was similar to 2-acetylthiophene and 2-furaldehyde,

and the yields for substrates containing electron-withdrawing groups were lower than those for substituents containing

electron-donating group.

a

Table 6. Palladium-catalyzed direct C(2)-arylation of 4,5-dimethylthiazole with (hetero)aryl bromides.

b

Entry

Aryl bromide

[Pd]

Product

Yield (%)

78

70

74

84

88

65

74

68

74

78

69

76

72

76

79

63

73

70

75

84

57

72

69

73

78

72

65

82

85

88

1

2

3

4

5

6

7

8

9

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

2a

2b

2c

2d

2e

1

0

1

2

3

4

5

6

7

8

9

0

1

2

3

4

5

6

7

8

9

0

3

a

Conditions: [Pd] 2a-2e (0.01 mmol), 4,5-dimethylthiazole (2.0 mmol), aryl bromide (1.0 mmol), KOAc (1.5 mmol), DMAc (2 mL), 140 °C, 1 h.

GC yields were calculated with respect to aryl bromide from the results of GC spectrometry with dodecane as internal standard.

b

The role of the steric and electronic effects plays on the catalytic activity for NHC ligands was investigated using

41

a variety of techniques in the literature. Even though benzimidazol-2-ylidenes have received limited attention as

NHC ligands, they provide a suitable platform for tuning the electron density on the carbene carbon. It is known that

by introducing electronically different substituents at the C5- and C6-positions of the benzimidazol-2-ylidene ligand, it

is possible to remotely change the electronic property of the Pd center without altering the steric environment in the

29a

metal. Also, altering the N-substituent would allow the topography around the metal to be tuned to ensure the

required steric bulk for reductive elimination is in place. Therefore, we preferred benzimidazol-2-ylidene ligands with

oxygen-donor and/or sterically bulky benzyl substituents. Of the Pd-complexes 2c-2e with 3-methoxybenzyl

substituent, progressively better results were seen as the number of methyl groups of the N-benzyl rings were increased

from mono-methyl to tri-methyl to tetra-methyl. In contrast, in aliphatic n-butyl substituted Pd-complexes 2a and 2b,

it appears that complex 2a containing benzyl ring gives better results than complex 2b containing sterically bulky

2

,3,4,5,6-pentamethylbenzyl ring. Since the σ-donor abilities of carbene ligands of 2c-2e complexes are similar, steric

factors are likely at work in the improved performance of 2e complex. However, for 2a and 2b complexes which

bearing n-butyl substituent, the steric effects have not significant effect on the catalytic activity. As a result, we believe

that such substituents on the NHC ligands provides the steric and electronic effects to confer the Pd center the

appropriate properties to make optimum to key steps of the catalytic cycles.

The Pd-catalyzed direct arylation of five-membered heteroaromatics with various arylating reagents has been

21-23,32,33

reported in some previous studies.

In these previous studies, similar substrates were used with higher catalyst

loading (1-20 mol%) and higher reaction times (1-48 h) were preferred for the direct arylation of heteroaromatics in

the presence of Pd-catalysts. In the present work, 1 mol% catalyst loading was used, and the reaction time was

shortened to 1 h. Moreover, five-membered heteroaromatics such as thiophene, furan and thiazole derivatives could be

efficiently and selectively arylated at the C(5)- or C(2)-position. In this study, satisfactory results were obtained as

32,33a

compared to previously reported similar studies using (hetero)aryl bromides.

Finally, the catalytic activities of the

new 2a-2e Pd-complexes were investigated in the direct C(5)- or C(2)-arylation of five-membered heteroaromatics. In

all cases, except in a few cases with complex 2d and 2e, high yields of the (hetero)aryl bromides were observed. Only

a minor effect of the NHC ligand on the Pd-complex was observed for the coupling of (hetero)aryl bromide with

heteroaromatics. Surprisingly, similar conversions were obtained for the coupling of each (hetero)aryl bromides. We

can say that there is no significant difference between these complexes on the catalytic activity of direct arylation of

heteroaromatics by (hetero)aryl bromides. The only significant difference between 2a-2e complexes indicates that

electronic and steric effects are also playing some role in these processes.

3

. Conclusion

In summary, we prepared a series of five new PEPPSI-type Pd-NHC complexes. These complexes were characterized

using different techniques. The catalytic activities of the new Pd-complexes were investigated in the direct C(5)- or

C(2)-arylation of five-membered heteroaromatics with (hetero)aryl bromides. It was found that the new Pd-complexes

were effective catalysts for the direct arylation reactions. Overall except in a few cases, satisfactory results were

obtained in all trials. Surprisingly, similar yields were obtained for the coupling of each (hetero)aryl bromides. Since

the NHC ligands used were similar to each other, no significant difference was observed between the catalytic

activities of Pd-complexes. This study was performed by using 1 mol% of palladium catalyst. Therefore, this low

catalyst loading procedure was economically attractive. In this study, only AcOH and HBr were formed as a by-

products by the use of direct arylation method and thus the by-product formation was minimized compared to the

multi-step traditional transition metal-catalyzed reactions. Also, this study contributes both organometallic synthesis

and the literature in the preparation of bi(hetero)aryl derivatives.

4

. Experimental

4

.1. General procedure for the preparation of benzimidazolium salts (1a-1e)

N-(Benzyl)-benzimidazole derivative (5.0 mmol) was dissolved in degassed DMF (3 mL) and alkyl halide (5.0 mmol)

was added at room temperature. The reaction mixture was stirred at 80 °C for 36 h under argon. After completion of

the reaction, the solvent was removed by vacuum and Et O (15 mL) was added to obtain a white crystalline solid,

2

which was filtered off. The solid was washed with Et O (3×10 mL) and dried under vacuum. The crude product was

2

recrystallized from EtOH/Et O mixture (1:5, v/v) at room temperature, and completely dried under vacuum. All

2

1

benzimidazolium salts (1a-1e) were isolated as air- and moisture-stable white solids in high yields. For the H NMR,

C NMR and FT-IR spectrums of the new 1d benzimidazolium salt see SI, pp. S1-S2.

13

4

.1.1. 1-(Benzyl)-3-(n-butyl)-benzimidazolium bromide, (1a)

34

This benzimidazolium salt was synthesized according to a published procedure.

4

.1.2. 1-(2,3,4,5,6-Pentamethylbenzyl)-3-(n-butyl)-benzimidazolium chloride, (1b)

35

This benzimidazolium salt was synthesized according to a published procedure.

4

.1.3. 1-(4-Methylbenzyl)-3-(3-methoxybenzyl)-benzimidazolium bromide, (1c)

36

This benzimidazolium salt was synthesized according to a published procedure.

4

.1.4. 1-(2,4,6-Trimethylbenzyl)-3-(3-methoxybenzyl)-benzimidazolium bromide, (1d)

o

-1

1

o

Yield 90%, 1.83 g; m.p. 199─200 C; white solid; FT-IR ν₍= 1553 cm . H NMR (400 MHz, CDCl , 25 C, TMS):

CN)

3

δ (ppm) = 2.22 and 2.26 (s, 9H, NCH Ph(CH ) -2,4,6); 3.73 (s, 3H, NCH Ph(OCH )-3); 5.82 (s, 4H, NCH Ph(CH ) -

2

3 3

2

3

2

3 3

2

,4,6 and NCH Ph(OCH )-3); 6.77-7.19 (m, 5H, arom. Hs of benzimidazole and 3-methoxybenzyl); 7.21 (s, 2H, arom.

2 3

Hs of 2,4,6-trimethylbenzyl); 7.32-7.52 (m, 3H, arom. Hs of benzimidazole and 3-methoxybenzyl); 11.74 (s, 1H,

13

o

NCHN). C NMR (101 MHz, CDCl , 25 C, TMS): δ (ppm) = 20.3 and 21.1 (NCH Ph(CH ) -2,4,6); 47.5

3

2

3 3

(

NCH Ph(CH ) -2,4,6); 51.4 (NCH Ph(OCH )-3); 55.6 (NCH Ph(OCH )-3); 113.6, 113.7, 113.8, 114.8, 120.1, 125.1,

2 3 3 2 3 2 3

1

27.0, 127.1, 130.2, 130.4, 131.5, 134.4, 137.9, 139.7 and 160.3 (arom. Cs of benzimidazole, 2,4,6-trimethylbenzyl

and 3-methoxybenzyl); 144.2 (NCHN). Elemental analysis calcd. (%) for C H BrN O: C 66.52, H 6.03, N 6.21;

25

27

2

found (%): C 66.96, H 6.22, N 6.31.

4

.1.5. 1-(2,3,5,6-Tetramethylbenzyl)-3-(3-methoxybenzyl)-benzimidazolium bromide, (1e)

37

This benzimidazolium salt was synthesized according to a published procedure.

4

.2. General procedure for the preparation of palladium complexes (2a-2e)

Benzimidazolium salts (1a-1e) (1.0 mmol) were converted with high yields into the PEPPSI-type palladium-NHC

complexes (2a-2e) by reaction with PdCl (1.0 mmol) in refluxing pyridine in the presence of K CO (5.0 mmol) as a

2

3

o

base at 80 C for 16 h. Volatiles were removed in vacuo, and the residue was washed with n-pentane (2×5 mL). The

crude product was dissolved with CH Cl then filtered through a pad of celite and silica gel (70-230 mesh) to remove

2

the unreacted PdCl and benzimidazolium salt. Then, the crude complex was crystallized from CH Cl /n-pentane

2

mixture (1:5, v/v) at room temperature and, completely dried under vacuum. Since the 1c-1e benzimidazolium salts

have the bromide anion, the synthesized Pd-complexes could be formed as mixtures containing bromine and chlorine.

We were synthesized only bromine-containing 2c-2e Pd-complexes by adding a large excess of KBr in the reaction to

prevent the formation of the different anions-containing Pd-complex mixtures. All Pd-complexes were isolated as air-

1

13

and moisture-stable yellow solids in 71%-83% yields. For the H NMR, C NMR and FT-IR spectrums of the new 2a-

2

e complexes see SI, pp. S3-S12.

4

.2.1. Dibromo-[1-(benzyl)-3-(n-butyl)-benzimidazole-2-ylidene]-(pyridine)-palladium(II), (2a)

o

-1

1

o

Yield 78%, 0.406 g; mp = 202─203 C; yellow solid; FT-IR ν₍= 1403 cm . H NMR (400 MHz, CDCl , 25 C,

CN)

3

TMS): δ (ppm) = 1.01 (t, J = 7.3 Hz, 3H, NCH CH CH CH ); 1.51 (hext, J = 7.4 Hz, 2H, NCH CH CH CH ); 2.15

2

3

2

3

(

pent, J = 7.4 Hz, 2H, NCH CH CH CH ); 4.86 (t, J = 7.8 Hz, 2H, NCH CH CH CH ); 6.23 (s, 2H, NCH Ph); 6.99-

2 2 2 3 2 2 2 3 2

7

1

.02, 7.05-7.09, 7.14-7.23 and 7.27-7.34 (m, 11H, arom. Hs of benzimidazole, benzyl and pyridine); 7.70 (tt, J = 7.5,

.5 Hz, 1H, arom. H of pyridine); 8.89 (dd, J = 6.5, 1.5 Hz, 2H, arom. Hs of pyridine). C NMR (101 MHz, CDCl , 25

3

13

o

C, TMS): δ (ppm) = 13.9 (NCH CH CH CH ); 20.4 (NCH CH CH CH ); 31.7 (NCH CH CH CH ); 48.6

2

3

2

3

2

3

(

NCH CH CH CH ); 49.1 (NCH Ph); 110.5, 111.1, 123.0, 123.2, 128.9, 130.6, 130.8, 134.2, 134.9 and 138.1 (arom.

2 2 2 3 2

Cs of benzimidazole and benzyl); 124.5, 137.4 and 151.3 (arom. Cs of pyridine); 164.3 (Pd-C_c_a_r_b_e_n_e). Elemental

analysis calcd. (%) for C H Br N Pd: C 45.31, H 4.13, N 6.89; found (%): C 47.28, H 3.82, N 7.11.

23

25

2

3

4

.2.2. Dichloro-[1-(2,3,4,5,6-pentamethylbenzyl)-3-(n-butyl)-benzimidazole-2-ylidene]-(pyridine)-palladium(II),

(2b)

o

-1

1

o

Yield 71%, 0.419 g; mp = 196─197 C; yellow solid; FT-IR ν₍= 1409 cm . H NMR (400 MHz, CDCl , 25 C,

CN)

3

TMS): δ (ppm) = 1.09 (t, J = 7.4 Hz, 3H, NCH CH CH CH ); 1.61 (hext, J = 7.5 Hz, 2H, NCH CH CH CH ); 2.23

2

3

2

3

(

pent, J = 7.4 Hz, 2H, NCH CH CH CH ); 2.23, 2.30 and 2.31 (s, 15H, NCH Ph(CH ) -2,3,4,5,6); 4.91 (t, J = 7.8 Hz,

2 2 2 3 2 3 5

2

6

H, NCH CH CH CH ); 6.27 (s, 2H, NCH Ph(CH ) -2,3,4,5,6); 6.38 (d, J = 8.6 Hz, 1H arom. H of benzimidazole),

2 2 2 3 2 3 5

.90-6.94 (m, 1H arom. H of benzimidazole), 7.12-7.16 (m, 1H arom. H of benzimidazole), 7.34-7.38 (m, 3H, arom.

Hs of benzimidazole and pyridine); 7.78 (tt, J = 7.7, 1.6 Hz, 1H, arom. H of pyridine); 8.98 (dd, J = 6.5, 1.5 Hz, 2H,

13

o

arom. Hs of pyridine). C NMR (101 MHz, CDCl , 25 C, TMS): δ (ppm) = 13.9 (NCH CH CH CH ); 16.9, 17.3 and

3

2

3

1

7.4 (NCH Ph(CH ) -2,3,4,5,6); 20.4 (NCH CH CH CH ); 31.7 (NCH CH CH CH ); 48.4 (NCH CH CH CH ); 51.3

2 3 5 2 2 2 3 2 2 2 3 2 2 2 3

(

NCH Ph(CH ) -2,3,4,5,6); 110.1, 111.7, 122.5, 122.9, 127.8, 133.1, 134.5, 134.6, 134.8 and 135.9 (arom. Cs of

2 3 5

benzimidazole and 2,3,4,5,6-pentamethylbenzyl); 124.5, 138.1 and 151.2 (arom. Cs of pyridine); 162.9 (Pd-C_c_a_r_b_e_n_e).

Elemental analysis calcd. (%) for C H Cl N Pd: C 56.91, H 5.97, N 7.11; found (%): C 56.96, H 5.86, N 7.10.

28

35

2

3

4

.2.3.

Trans-Dibromo-[1-(4-methylbenzyl)-3-(3-methoxylbenzyl)-benzimidazole-2-ylidene]-(pyridine)-

palladium(II), (2c)

o

-1

1

o

Yield 83%, 0.570 g; mp = 222─223 C; yellow solid; FT-IR ν₍= 1409 cm . H NMR (400 MHz, CDCl , 25 C,

CN)

3

TMS): δ (ppm) = 2.32 (s, 3H, NCH Ph(CH )-4); 3.75 (s, 3H, NCH Ph(OCH )-3); 6.18 (s, 4H, NCH Ph(CH )-4 and

2

3

2

3

2

3

NCH Ph(OCH )-4); 6.86 (d, J = 7.4 Hz, 1H arom. H of 4-methylbenzyl), 7.03-7.31 (m, 11H, arom. Hs of

2

3

benzimidazole, 3-methoxylbenzyl and 4-methylbenzyl); 7.50 (d, J = 7.9 Hz, 2H, arom. Hs of pyridine); 7.72 (tt, J =

1

3

7

.7, 1.6 Hz, 1H, arom. H of pyridine); 9.02 (dd, J = 6.5, 1.5 Hz, 2H, arom. Hs of pyridine). C NMR (101 MHz,

o

CDCl , 25 C, TMS): δ (ppm) = 21.2 (NCH Ph(CH )-4); 53.5 (NCH Ph(CH )-4); 53.7 (NCH Ph(OCH )-4); 55.7

3

2

3

2

3

2

3

(

NCH Ph(OCH )-4); 111.5, 111.6, 113.1, 114.7, 120.4, 123.1, 128.0, 129.5, 129.7, 131.8, 134.7, 134.8, 136.6, 137.8

2 3

and 160.2 (arom. Cs of benzimidazole, 3-methoxylbenzyl and 4-methylbenzyl); 124.5, 137.9 and 153.0 (arom. Cs of

pyridine); 164.2 (Pd-C_c_a_r_b_e_n_e). Elemental analysis calcd. (%) for C H Br N OPd: C 48.90, H 3.96, N 6.11; found (%):

28

27

2

3

C 49.22, H 3.94, N 6.17.

4

.2.4.

Dibromo-[1-(2,4,6-trimethylbenzyl)-3-(3-methoxylbenzyl)-benzimidazole-2-ylidene]-(pyridine)-

palladium(II), (2d)

o

-1

1

o

Yield 75%, 0.536 g; mp = 247─248 C; yellow solid; FT-IR v = 1395 cm . H NMR (400 MHz, CDCl , 25 C,

CN

3

TMS): δ (ppm) = 2.35 and 2.37 (s, 9H, NCH Ph(CH ) -2,4,6); 3.75 (s, 3H, NCH Ph(OCH )-3); 6.19 (s, 4H,

2

3 3

2

3

NCH Ph(CH ) -2,4,6 and NCH Ph(OCH )-4); 6.85-6.89 and 6.98-7.30 (m, 8H, arom. Hs of benzimidazole and 3-

2

3 3

2

3

methoxylbenzyl); 6.95 (s, 2H arom. Hs of 2,4,6-trimethylbenzyl), 7.34 (t, J = 7.6 Hz, 2H, arom. Hs of pyridine); 7.75

1

3

(

tt, J = 7.5, 1.5 Hz, 1H, arom. H of pyridine); 9.03 (dd, J = 7.5, 1.5 Hz, 2H, arom. Hs of pyridine). C NMR (101

o

MHz, CDCl , 25 C, TMS): δ (ppm) = 21.0 and 21.1 (NCH Ph(CH ) -2,4,6); 51.1 (NCH Ph(CH ) -2,4,6); 53.8

3

2

3 3

2

3 3

(

NCH Ph(OCH )-4); 55.7 (NCH Ph(OCH )-4); 111.3, 113.1, 114.6, 120.3, 122.7, 123.1, 127.5, 129.6, 129.7, 134.6,

2 3 2 3

1

35.2, 136.6, 137.9, 139.0 and 160.2 (arom. Cs of benzimidazole, 3-methoxylbenzyl and 2,4,6-trimethylbenzyl);

24.5, 138.7 and 152.6 (arom. Cs of pyridine); 164.0 (Pd-C_c_a_r_b_e_n_e). Elemental analysis calcd. (%) for C H Br N OPd:

30

31

2

3

C 50.34, H 4.37, N 5.87; found (%): C 49.71, H 4.43, N 5.83.

4

.2.5.

Dibromo-[1-(2,3,5,6-tetramethylbenzyl)-3-(3-methoxybenzyl)-benzimidazole-2-ylidene]-(pyridine)-

palladium(II), (2e)

o

-1

1

o

Yield 80%, 0.583 g; mp = 213─214 C; yellow solid; FT-IR ν₍= 1405 cm . H NMR (400 MHz, CDCl , 25 C,

CN)

3

TMS): δ (ppm) = 2.31 (s, 12H, NCH Ph(CH ) -2,3,5,6); 3.79 (s, 3H, NCH Ph(OCH )-3); 6.22 (s, 2H, NCH Ph(CH ) -

2

3 4

2

3

2

3 4

2

,3,5,6); 6.26 (s, 2H, NCH Ph(OCH )-4); 6.85-7.31 (m, 11H, arom. Hs of benzimidazole, 3-methoxylbenzyl and

2 3

,3,5,6-tetramethylbenzyl); 7.36 (t, J = 7.5 Hz, 2H, arom. Hs of pyridine); 7.78 (tt, J = 7.5, 1.5 Hz, 1H, arom. H of

13

o

pyridine); 9.03 (dd, J = 6.5, 1.5 Hz, 2H, arom. Hs of pyridine). C NMR (101 MHz, CDCl , 25 C, TMS): δ (ppm) =

3

1

6.8 and 20.6 (NCH Ph(CH ) -2,3,5,6); 51.6 (NCH Ph(CH ) -2,3,5,6); 53.9 (NCH Ph(OCH )-4); 55.7

2 3 4 2 3 4 2 3

(

NCH Ph(OCH )-4); 111.3, 113.1, 114.6, 120.4, 122.6, 123.1, 129.7, 130.5, 132.6, 134.4, 134.5, 135.2, 135.4, 137.9

2 3

and 160.2 (arom. Cs of benzimidazole, 3-methoxylbenzyl and 2,3,5,6-tetramethylbenzyl); 124.5, 136.7 and 152.6

(

arom. Cs of pyridine); 163.9 (Pd-C_c_a_r_b_e_n_e). Elemental analysis calcd. (%) for C H Br N OPd: C 51.02, H 4.56, N

31 33 2 3

5

.76; found (%): C 52.95, H 5.06, N 5.71.

.3. General procedure for the direct arylation of five-membered heteroaromatics

4

In a typical experiment, an oven dried 10 mL Schlenk tube was charged with 1 mol% Pd-complex, (0.01 mmol), as

catalyst, five-membered heteroaromatic compound (2.0 mmol), (hetero)aryl bromide (1.0 mmol), KOAc (1.5 mmol) as

o

a base, and DMAc (2 mL) as solvent under an argon atmosphere. The reaction mixture was stirred at 120 C or 140 C

for 1 h (see Table 4-6). After completion of the reaction, the solvent was evaporated under vacuum and the residue was

solved with CH Cl (2 mL). The chemical characterizations of the products were undertaken with GC and GC-MS

2

spectrometry. GC yields were calculated with respect to aryl bromide from the results of GC spectrometry with

dodecane as internal standard.

4

.4. X-ray Analysis

Intensity data of 2c were collected on a STOE IPDS II diffractometer at room temperature using graphite-

monochromated Mo Kα radiation by applying the ω-scan method. Data collection and cell refinement were carried out

4

2

42

using X-AREA while data reduction was applied using X-RED32 . The structure was solved by a dual-space

43

2

44

algorithm using SHELXT-2018 and refined with full-matrix least-squares calculations on F using SHELXL-2018

implemented in WinGX program suit. All carbon-bound H atoms were located in difference electron-density map

45

and then treated as riding atoms in geometrically idealized positions, with C─H = 0.93 (aromatic), 0.97 (CH ) and 0.96

2

Å (CH ), and with U (H) = kU (C), where k = 1.5 for the methyl groups and 1.2 for all other H atoms. In the

3

iso

eq

compound, the methoxy moiety was disordered over two positions, and the refined site-occupancy factors of the

disordered parts, viz. O1A─C15A and O1B─C15B, are 0.673(15) and 0.327(15)%, respectively. In the final difference

−3

Fourier map of the compound, the maximum residual densities being higher than 1 e Å were observed around the

palladium and essentially meaningless. The crystallographic data and refinement parameters are summarized in Table

45

7

. Molecular graphic was created by using ORTEP-3.

Table 7. Crystal data and structure refinement parameters for 2c.

CCDC depository

Color/shape

1910749

Colorless/plate

Chemical formula

Formula weight

Temperature (K)

Wavelength (Å)

Crystal system

Space group

2 22 2 5 5

[PdBr (C23H N O)(C H N)]

687.74

296

0.71073 Mo Kα

Monoclinic

1

P2 /n (No. 14)

Unit cell parameters

a, b, c (Å)

12.0678(6), 11.2435(6), 20.8956(10)

α, β, γ (°)

Volume (Å )

Z

90, 106.548(4), 90

2717.8(2)

4

1.681

3.649

3

D

ꢀ

calc. (g/cm )

(mm )

−1

Absorption correction

Integration

0.1835, 0.8479

1360

Tmin., Tmax.

F

000

3

Crystal size (mm )

0.48 × 0.41 × 0.03

Diffractometer/measurement STOE IPDS II/rotation (ω scan)

Index ranges −15 ≤ h ≤ 15, −14 ≤ k ≤ 14, −27 ≤ l ≤ 27

θ range for data collection (°) 2.033 ≤ θ ≤ 27.692

Reflections collected

Independent/observed

26986

6342/3458

R

int.

0.110

2

Refinement method

Data/restraints/parameters

Goodness-of-fit on F

Full-matrix least-squares on F

6342/41/339

0.955

2

Final R indices [I > 2σ(I)]

R

1

= 0.0568, wR

= 0.1177, wR

2

= 0.1163

= 0.1374

R indices (all data)

1

3

ꢀρ

max., ꢀρmin. (e/Å )

1.11, −0.40

Appendix A. Supplementary data

CCDC 1910749 for 2c complex contains the supplementary crystallographic data for the compound reported in this

article. These data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK

[

Fax: +44 1223 336 033, e-mail: deposit@ccdc.cam.ac.uk, https://www.ccdc.cam.ac.uk/structures/].

Supplementary data related to this article can be found at https://

Acknowledgements

This study was supported by the Ondokuz Mayıs University (Project No: PYO.FEN.1906.19.001) and the

Technological and Scientific Research Council of Turkey TÜBİTAK (Project No: 117R010).

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Highlights

•

Benzimidazole-based PEPPSI-type palladium-complexes were synthesized.

The structures of palladium-complexes were characterized by different techniques.

The complexes were tested as catalysts in the direct arylation of five-membered heteroaromatics.

Declaration of interests

☒

The authors declare that they have no known competing financial interests or personal relationships

that could have appeared to influence the work reported in this paper.

☐

The authors declare the following financial interests/personal relationships which may be considered

as potential competing interests:

Article Doi

Palladium-carbene catalyzed direct arylation of five-membered heteroaromatics

DOI: 10.1016/j.molstruc.2019.127668

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Article abstract of DOI:10.1016/j.molstruc.2019.127668

Full text of DOI:10.1016/j.molstruc.2019.127668

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