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Current Organic Chemistry, 2019, 23, 1601-1662 1601

REVIEW ARTICLE

1385-2728/19 $58.00+.00 © 2019 Bentham Science Publishers

Recent Advances in Synthesis and Uses of Heterocycles-based Palladium(II) Com-plexes as Robust, Stable, and Low-cost Catalysts for Suzuki- Miyaura Cross-couplings

Mohamed R. Shaaban1,2,*, Thoraya. A. Farghaly1,2, Afaf Y. Khormi2 and Ahmad M. Farag1

1Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt; 2Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukaramah, Saudi Arabia

A R T I C L E H I S T O R Y

Received: February 02, 2019 Revised: May 16, 2019 Accepted: May 16, 2019 DOI: 10.2174/1385272823666190620121845

Abstract: C-C cross-couplings constitute the largest diversity of organic reactions of chemical, biomedical, and industrial significance. They are also among the most fre-quently encountered reactions used in the synthesis of numerous drugs and relevant phar-maceutical substances. Development of an easily accessed, efficient, stable, and low cost catalyst is an attractive area of research in such kind of organic synthesis. This review highlights the remarkable and recent achievements made recently in the synthesis and use of palladium(II) complexes catalysts, that are based on heterocycles as ligands in their constitution, in the Suzuki-Miyaura cross-coupling.

Keywords: Suzuki-Miyaura; cross-couplings; palladium(II) complexes; heterocycles; catalysis; biaryls.

1. INTRODUCTION

Biaryls and substituted aromatic structures, in general, consti-tute the cores of various natural products, ligands, pharmaceuticals and polymers [1-11]. Subsequently, efficient and green methods for synthesizing these compounds are decisive, to the work of a broad range of organic chemists. On the other hand, cross-coupling reac-tions with transition-metal-catalysts are considerably useful syn-thetic route for the synthesis of biaryls via C-C bonds formation [12-14]. The Suzuki-Miyaura cross-coupling (SMC) [15-20], has become a standard procedure for implementations, extending from pharmaceuticals to materials science [21]. It is quite familiar that the main feature of metal catalysts is their high catalytic efficiency, but unfavourable factors, such as pollution problems to the envi-ronment, difficulty in recycling and high price, have seriously con-erned their implementations in the industry. However, there has been considerable interest in the development of new, highly-active palladium catalysts that can be used in cross-coupling reactions [22-24]. Since the middle of the 20th century, the interest in palladium as a catalyst has been increased markedly. Traditionally, palladium intermediates were stabilized by using phosphine ligands [25]. However, the air-susceptibility of these kinds of ligands can prevent their use in a variety of synthetic implementations [26]. Moreover, phosphine ligands are often expensive, and their price can override the palladium salt. On the other hand, phosphorus-free palladium catalysts have many advantages such as high air stability, thermal stability, and higher catalytic activity which permit the catalysed

* Address correspondence to this author at the Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt; Tel: +966545917568; E-mail: [email protected]

reaction to occur under mild reaction conditions [27, 28]. Thus, the development of phosphine-free ligands has been increasingly de-veloped in the recent years, with amines, carbenes, thioureas, etc. [29, 30]. Construction of the appropriate ligands might be a good controlling factor to obtain catalysts that push the weak leaving group, such as chloride in SMC to take its role in the reaction and can be easily displaced. Also, the developed appropriate ligands will lead to catalysts that exhibit improved lifetimes, higher TON, recyclability and are stable to run the reactions in aerobic condi-tions at lower temperatures [31, 32]. In the course of many studies including our recent studies, on carbon-carbon bond-forming reac-tions [33-38], it was found that the utility of different heterocyclic compounds in complexation with palladium and their use in cataly-sis of SMC reactions; was the nucleus for the development of new series of ligands that could be used for a wide variety of reactions of palladium-catalyzed carbon-carbon coupling cross-coupling reactions. It should be noted that, the reaction yields that are men-tioned here in each contribution are only the maximum isolated yields using the optimized conditions of the base solvent, co-catalyst and catalyst loadings. In some cases, conversions are men-tioned if the isolated yields are not reported by the authors. The complexes or heterocyclic-based palladium catalysts are arranged according to the ring size, the number of heteroatoms and the benzo-fused heterocycles. When two heterocycles are present in the complex, the categorization is based on the smaller ring size hetero-cycle. In the present review, we shed light on the main strategies for the development of new heterocyclic-based palladium complexes and their uses as efficient catalysts for SMC over the last decade.

M.R. Shaaban

1602 Current Organic Chemistry, 2019, Vol. 23, No. 15 Shaaban et al.

2. FIVE MEMBERED HETEROCYCLES-BASED PALLA-DIUM COMPLEXES

2.1. Five-Membered with one Heteroatom Heterocycles-Based Palladium Complexes

2.1.1. Pyrrole-based Palladium Complexes Development of an efficient and convenient palladium(II)-

porphyrin catalytic system which was used for the Suzuki-Miyaura cross-coupling (SMC) of potassium aryltrifluoroborate with aryl bromides in water was achieved. A series of seven different porphy-rins and their complexes with palladium 2a-g, containing various substituents in the attached phenyl moiety, was synthesized. Thus, heating a mixture of substituted porphyrins 1 with palladium chlo-ride in dimethylformamide (DMF) afforded the corresponding pal-ladium(II)-porphyrin complexes 2a-g as shown in Scheme (1). It was found that, porphyrin-based complexes 2a-g were highly stable and moisture-resistant as compared with the toxic and unstable phosphine ligands containing complexes [39].

The catalytic activity of the synthesized palladium(II)-porphyrin complexes 2a-g in the synthesis of biaryl derivatives 5 through C-C coupling has been investigated using an aqueous me-dium (H2O) as a solvent (Scheme 2). The isolated products have been obtained in excellent yield (Table 1) regardless the nature of the substituent in the aryl bromide, using water as a solvent, and reusability of the catalyst were the remarkable advantages of this developed methodology. Moreover, the method was applied for larger-scale synthesis of biaryl derivatives without any side prod-ucts [39].

An efficient water-‐soluble palladium catalyst 7 with L-‐proline as N, O-‐ligand has been synthesized by Zhang et al. and used for the catalysis of aqueous Suzuki–Miyaura cross-coupling reaction. The L-proline-based palladium complex 7 was synthesized by addi-tion of triethylamine to a methanolic solution of L-‐proline 6 with stirring for 1 h, then; a methanolic solution of palladium acetate was then added to the reaction mixture with vigorous stirring under

NH

N HN

N

X

X

X

X

X = a, p-OH; b, p-COOH; c, H, d, m-SO3Na; e, m-CN; f, m-NO2; g, m-OMe

PdCl2/ DMF

D/ 150 oC/ 2 h

N

N N

N

X

X

X

XPd

12

Scheme 1. Synthesis of palladium(II)-porphyrin complexes 2a-g.

+ BNu

Conditions:Cat. conc.:0.05 mol%Solvent: H2O/DMF or H2OBase: K2CO3Co-catalyst:NoneTemperature:85 oC/ reflux (!)Time: 0.5-3 h

3 45

2

X

R1 R2R2R1

N

N N

N

X

X

X

XPd

3a, X = Br3b, X = I3c, X = Cl

Scheme 2. Suzuki–Miyaura cross-coupling reaction between different aryl bromides and substituted aryltrifluoroborate using 2 as precatalysts.

Recent Advances in Synthesis and Uses of Heterocycles-based Palladium(II) Current Organic Chemistry, 2019, Vol. 23, No. 15 1603

N2 until complex 7 precipitated at room temperature (Scheme 3) [40].

NH OH

O Pd(OAc)2

Et3N/ MeOH/ rt.

NHO

O

Pd

NHO

O6 7

Scheme 3. Synthesis of water-‐soluble palladium catalyst 7.

Using the optimized conditions as shown in Scheme (4), C-C coupling between aryl halides 3a-c and arylboronic acids 8 pro-

ceeded efficiently using water as a solvent, affording the desired biaryl derivatives 5 with good to excellent yields (Table 2). The recycling of the catalytic system was successful for at least 6 times [40].

2.2. FIVE-MEMBERED WITH TWO HETEROATOM HET-EROCYCLES-BASED PALLADIUM COMPLEXES

2.2.1. Pyrazole-based Palladium Complexes

The reaction of 4-aminoantipyrine 10 with dibenzoylmethane 9 in refluxing ethanol afforded a new Schiff base ligand 11 in high yield as shown in Scheme (5). The reaction of the pyrazolone-based ligand 11 with methanolic solution of palladium acetate at room temperature afforded the corresponding new greenish-yellow solid pyrazolone-palladium(II) complex 12 (Scheme 5) [41].

Table 1. Suzuki–Miyaura cross-coupling reaction between different aryl bromides and substituted aryltrifluoroborate using 2 as precatalysts.

Entry R1 BNu R2 Yield % TON TOF (h-1)

1 4-MeO B(OH)2 3-NO2 92 - -

2 4-MeO BKF3 3-NO2 98 - -

3 4-MeO

OB

O

3-NO2 86 -

4 4-MeO

OBO

3-NO2 80 - -

5 4-MeO

OB

NO

3-NO2 94 - -

6 4-MeO BKF3 H 89 1780 890

7 4-MeO BKF3 2,4-Me2- 88 1760 880

8 4-MeO BKF3 3,4-Me2- 89 1780 890

9 4-MeO BKF3 4-tBu 85 1700 567

10 4-MeO BKF3 4-Ac 93 1860 1240

11 4-MeO BKF3 3-SO2Me 95 1900 1267

12 4-MeO BKF3 2-CN 93 1860 1860

13 4-MeO BKF3 4-NO2 98 1960 3920

14 4-MeO BKF3 4-Cl 95 1900 1900

15 4-MeO BKF3 4-CHO 94 1880 940

16 4-MeO BKF3 3-COOH 91 1820 910

17 4-MeO BKF3 3-F 90 1800 1800

18 4-COOMe BKF3 3-NO2 91 1880 1820

19 4-NO2 BKF3 3-NO2 94 1800 1880

20 4-NO2 BKF3 3-NO2 90 1800 1800

21 4-Me BKF3 3-NO2 90 1800 900

22 4-Et BKF3 3-NO2 92 1840 920

23 3-MeO BKF3 3-NO2 94 1880 1880

24 2-Et BKF3 3-NO2 91 1820 910

25 2-Naphthyl BKF3 3-NO2 87 1740 870


NHO

O

Pd

NHO

O

Conditions:Cat. conc.0.01-0.2 mol%Solvent: H2OBase: K2CO3Co-catalyst: noneTemperature:100 oC/!Time:2-20 h

+ BOH

OH

3a-c 8a-d

X

R1R1R2

7

5

R2

8, R2 = a, H; b, 4-OMe; c, 4-Ac; d, 4-OH Scheme 4. Suzuki–Miyaura cross-coupling reaction between different aryl halides and arylboronic acids using complex 7 as a precatalyst. Table 2. Suzuki–Miyaura cross-coupling reaction between different aryl halides and arylboronic acids using complex 7 as a precatalyst.

Entry X R1 R2 Yield %

1 I H H 97

2 I 4-OH H 93

3 I 4-MeO H 96

4 I 4-F H 96

5 I 4-NO2 H 95

6 I 3-NO3 H 96

7 I 4-Ac H 96

8 Br H H 98

9 Br 4-CH2OH H 94

10 Br 4-Me H 92

11 Br 4-Cl H 91

12 Br 3-NO2 H 98

13 Br 4-CHO H 96

14 Br 4-Ac H 96

15 Br 4-COOH H 90

16 Br 4-NH2 H 90

17 Br 2-CHO H 92

18 I 2-MeO H 95

19 Cl 4-Ac H 12

20 I H 4-MeO 94

21 I 4-F 4-MeO 94

22 I 4-Ac 4-MeO 94

23 Br 4-Ac 4-MeO 92

24 I H 4-Ac 90

25 I 4-MeO 4-Ac 83

26 I 4-AC 4-Ac 84

27 Br 4-Ac 4-Ac 89

28 Br 4-CH2OH 4-Ac 96

29 Br 4-CHO 4-Ac 91

30 Br H 4-OH 87

31 Br 4-CHO 4-OH 35

32 Br 4-CHO 4-OH 90


Pd(AcO)2

OO

NN

OH2N

+

NN

ON

OH

EtOH/ 4h !

NN

O

N

O

NN

O

N

OPd

MeOH/rt, 12 h

9

10 11 12 Scheme 5. Synthesis of water-‐soluble palladium catalyst 12.

Conditions:Cat. conc.:0.2 mol%Solvent: H2O/DMFBase: K2CO3Co-catalyst: noneTemperature:80 oC/ !Time: 3-6 h

+ BOH

OH

3 a,b or 13 (Z =N) 8

Z

X

ZR2R1

R1

R2

N NO

N

O

NNO

N

O Pd

12

5 or 14

Scheme 6. Suzuki–Miyaura cross-coupling reaction between different aryl or pyridylhalides and arylboronic acids using complex 12 as a precatalyst.

The catalytic activity of the pyrazolone-based palladium com-plex 12 has been examined using the reaction between 4-methoxybromobenzene as an example of aryl bromide 3a and 4-methylphenylboronic acid 8 as a model reaction (Scheme 6). It was found that, this catalytic system was efficient for the synthesis of biaryls 5 in excellent yields without using any co-catalyst with mild reaction conditions (Table 3) [41]. The same catalytic system has been used for the cross coupling of 2-bromopyridine 13 and phen-ylboronic acid to afford the corresponding 2-phenylpyridine in good yield under the same reaction conditions as shown in Table (3).

5-Methoxy-1-pyridin-2-yl-1H-pyrazole-3-carboxylic acid 15 have been synthesized by Liqun et al and used as a ligand and pre-cursor for the novel pre-catalyst 16 via its reaction with potassium tetrachloropalladate in aqueous methanol at room temperature as shown in Scheme (7) [42].

Under the developed optimized conditions, complex 16 was an efficient catalyst for microwave-assisted Suzuki–Miyaura cross-

coupling reaction between a wide range of aryl halides and arylbo-ronic acids as depicted in Table (4). In general, the catalyst found to be very efficient when electron-rich or electron-poor aryl halides were utilized under microwave irradiation in water/EtOH co-solvent as a green methodology for the synthesis of biaryl 5 as shown in Scheme (8) [42].

2.2.2. 1,3-Oxazole-based Palladium Complexes

Novel bis(oxazoline) ligand 19 was simply synthesized by re-acting 2-‐amino-‐2-‐methyl-‐1-‐propanol 18 with phthalonitrile 17 in the presence of zinc triflate as a catalyst. The bis(oxazoline) palla-dium complex 20 was prepared by the reaction of 19 with bis(benzonitrile)palladium(II) chloride in dimethylformamide as shown in Scheme (9) [43]. Other unsymmetrical structural related complexes have been synthesized using the same experimental conditions to afford the corresponding palladium complexes 21 and 22 (Fig. 1).


Table 3. Suzuki–Miyaura cross-coupling reaction between different aryl or pyridylhalides and arylboronic acids using complex 12 as a precata-lyst.

Entry X Z R1 R2 Yield % TON TOF (h-1)

1 Br CH H H 91 470 105

2 Br CH H 4-Me 92 475 118

3 Br CH MeO 4-Me 95 514 129

4 Br CH Ac H 93 480 120

5 Br CH MeO 4-MeO 92 477 119

6 I CH MeO 4-Me 94 509 145

7 Br CH H 4-Et 90 464 116

8 Br CH H 4-MeO 92 475 119

9 Br CH MeO 4-Et 93 504 112

10 Br CH H 3-Me 90 464 103

11 Br CH H 4-Cl 89 459 102

12 Br CH MeO 4-Cl 90 464 103

13 Br CH H 3-CN 88 476 106

14 Br CH MeO 4-F 87 471 105

15 Br N H H 72 332 74

K2PdCl4

MeOH/ H2ON N

N

OCH3

COOH

N N

N

OCH3

COOH

PdCl

Cl

15 16

Scheme 7. Synthesis of pyrazole based palladium catalyst 16.

N N

N

OCH3

COOH

PdCl

Cl

Conditions:Cat. conc.:0.1 mol%Solvent: H2O/EtOHBase: KOHCo-catalyst: TBABTemperature: 120 oC/ !w(60 w)Time: 2 min

+ BOH

OH

3a-c 8

X

R1R1R2 R2

5

16

Scheme 8. Suzuki–Miyaura cross-coupling reaction between different aryl halides and arylboronic acids using complex 16 as a precatalyst.


Table 4. Suzuki–Miyaura cross-coupling reaction between different aryl halides and arylboronic acids using complex 16 as a precatalyst.


1 Br 4- CHO H 90.3

2 Br 3-CHO H 85.1

3 Br 2-CHO H 80.3

4 Br 4-MeO H 86.7

5 Br 4-Me H 82.4

6 Br 4-OH H 93

7 Br 4-Ac H 92.6

8 Br 4-Cl H 90.8

9 Br H H 86.7

10 I H H 91.3

11 Cl H H 63.8

12 Cl 2-COOH H 75.5

13 Cl 4-NO2 H 88.3

14 Br 4-CHO 4-MeO 92.7

15 Br 3-CHO 4-MeO 87.7

16 Br 2-CHO 4-MeO 83.5

17 Br 4-MeO 4-MeO 88.1

18 Br 4-Me 4-MeO 85.3

19 Br 4-OH 4-MeO 93.2

20 Br 4-Ac 4-MeO 93.0

21 Br 4-Cl 4-MeO 91.2

22 Br H 4-MeO 90.8

23 I H 4-MeO 92.7

24 Cl H 4-MeO 67.2

25 Cl 2-COOH 4-MeO 78.4

26 Cl 4-NO2 4-MeO 89.0

CNNC

+

NH2

HO2

NOO

NZn(OTf)2

D/ 24h

PdCl2(PhCN)2

DMF/ rt./6 h

NOO

N

Pd

Cl Cl

17

18 19 20 Scheme 9. Synthesis of bis(oxazoline)-based palladium catalyst 20.

The new bis(oxazoline) palladium complex 20 showed excel-lent catalytic activity in Suzuki–Miyaura cross-‐coupling reactions. Various biaryl derivatives 5 have been synthesized in excellent isolated yields by the cross- coupling of arylhalides 3a-c with aryl-boronic acids 8 (Scheme 10, Table 5) [43]. The catalytic system can

tolerate a wide range of substituents on aryl halides and arylboronic acids in DMF/H2O (1:1) as a solvent system at room temperature (Table 5). It was reported that the exceptional catalytic activity observed with bis(oxazoline) palladium complex 20 can be attrib-uted to both electronic and steric effects. Furthermore, the newly


developed catalyst showed high recyclability of more than 12 times without losing its activity in the coupling reactions [43].

2.2.3. Isoxazole-based Palladium Complexes Replacement of the acetonitrile ligands in bis(acetonitrile) di-

chloropalladium(II) by the aminoisoxazole ligands 23 afforded the corresponding dichloropalladium(II)–bis[5-(4-tolyl) isoxazol-3-amine] complex 24 in excellent yield (Scheme 11) [44].

NOH2N

PdCl2(MeCN)2NO

NH2

N O

H2N

PdCl

Cl

23 24 Scheme 11. Synthesis of complex 24.

NOO

N

Pd

Cl Cl

PhO

NOO

N

Pd

Cl Cl

PhO

21 22

Fig. (1). Representation of structures of Pd(II) complexes 21 and 22.

Conditions:Cat. conc.:0.002 mmolSolvent: DMF/H2OBase: K2CO3Co-catalyst: noneTemperature: rt. or 120 oCTime: 0.3-12 h

+ BOH

OH

3a-c 8

X

R1R1R2 R2

NOO

N

Pd

Cl Cl20

5


Table 5. Suzuki–Miyaura cross-coupling reaction between different aryl halides and arylboronic acids in DMF/H2O (1:1) as a solvent system using catalyst 20 at room temperature.


1 I 4-Ac H 98

2 I 4-Ac 4-Me 99

3 I 4-Ac 4-OH 97

4 I 4-Ac 3,4-OCH2O- 97

5 I 4-NO2 H 96

6 I H 4-OH 96

7 I H 4-Me 95

8 I 4-MeO H 93

9 I 4-NH2 H 94

10 Br 4-Ac H 99

11 Br 4-CHO H 99

12 Br 4-CN H 98

13 Br 2-MeO H 95

14 Br 4-Me H 98

15 Cl H 4-Me 89

16 Cl H 4-EtO 87

17 Cl H H 72

18 Cl 4-CHO H 95

19 Cl 4-CHO 4-Me 96


Firstly, the catalytic activity of the new complex 24, was exam-ined in the reaction of 3-bromobenzoic acid 25 with 4-substituted phenylboronic acid 8 in the presence of 24 using water as the sol-vent and in the presence of potassium carbonate as a base. The reac-tion proceeded under homogeneous conditions smoothly to give the corresponding coupled product 26 in 100% yield using the opti-mized reaction conditions as shown in the (Scheme 12) [44].

In addition, the catalytic ability of the new precatalyst 24 has been tested in reactions of water-insoluble aryl bromides. The cou-pling of 2-bromoaniline 3 and 4-methoxyphenylboronic acid 8 in water is shown in Scheme (13) [44].

Also, the novel isoxazole-based complex 24 showed high cata-lytic activity in the Suzuki–Miyaura cross-coupling reactions of aryl iodides under aerobic conditions and in water. It was found that, only 0.1 mol% palladium catalyst 24 was enough to produce the biaryl compounds 5 in quantitative yields with high turnover number as shown in Schemes (12) and (13).

2.2.4. Imidazole-based Palladium Complexes

Jayantjit et al. developed a robust and non-toxic catalytic sys-tem for cross-coupling reactions under room temperature with envi-ronmentally friendly conditions using N-methyl imidazole 29 as a co-ligand. The new complex 30 has been synthesized as shown in Scheme (14) starting from the complexation of ligand 27 then inter-conversion of pd(II) complex 28 to imidazole based pd(II) complex 30 via its reaction with N-methyl imidazole 29. N-methyl imidazole 29 was chosen as the co-ligand to increase the electron density at Pd. The advantages of the new complex 30 were its stability in air and moisture and solubility in some common organic solvents [45].

The synthesized complex 30 proved to be a highly active pre-catalyst for Suzuki-Miyaura cross-coupling reactions of aryl or heteroarylboronic acids 8 with aryl bromides or chlorides 3a,c at room temperature and at 60 °C, respectively, without using any additives or co-catalysts under mild conditions (Scheme 15, Table 6). It was found that, a low catalyst loading is required for the reac-

Conditions:Cat. conc.:0.01-0.001 mol%Solvent: H2OBase: Na2CO3Co-catalyst: noneTemperature: 100 oCTime: 5-10 min

+ BOH

OH

25 8

X

26

NO

H2NNO

NH2

Pd

Cl

Cl

COOH

R1

R1

HOOC

R2 R2

X = Br, R1= H , R2 = OMe, Yield = 100 %, TON =10000, TOF = 60000 h-1

X = I, R1= H , R2 = OMe, Yield = 100 %, TON =9800, TOF = 58800 h-1

X = I, R1= OH , R2 = H, Yield = 94 %, TON =9.4 x 105, TOF = 1.1 x 107 h-1

24


Conditions:Cat. conc.: 0.01-0.001 mol%Solvent: H2OBase: KOH or K2CO3Co-catalyst: noneTemperature: 100 oCTime: 10-15 min

+ BOH

OH

3a,b 8

X

NO

H2N

NO

NH2

Pd

Cl

Cl

X = Br, Yield = 100 %, TON =1000, TOF = 4000 h-1

X = I, Yield = 100 %, TON =10000, TOF = 198000 h-1

24

R2

R2 = 4-MeO

R1

R1 = 2-NH2

R1 = 2'-NH2, R2 = 4-MeO,

5

R2R1



tion and the complex 30 is converted to ∼1.5-2.0 nm-sized palla-dium nanoparticles which were considered to be the real catalytic species in the cross-coupling to give 5. The recyclability of the precatalyst 30 was achieved up to seven times without losing its activity [45].

A new 1-trityl-1H-imidazole-based palladium complex 32 has been synthesized by reacting 1-trityl-1H-imidazole 31 with palla-dium chloride in anhydrous THF at 60 oC as depicted in Scheme (16) [46].

The catalytic activity of the new imidazole-based palladium complex 32 for the Suzuki-Miyaura cross-coupling reaction of aryl chlorides 3c with phenylboronic acid 8 was investigated as pre-sented in Scheme (17) and Table 7. The reactions of arylboronic acids with aryl chlorides proceeded with good to excellent yields. A moderate yield was obtained for 4-methyl-1-naphthaleneboronic acid. However, much lower reactivity was observed for p-chloroacetophenone and 2-chloropyridine 13 (Table 7, Entries 8, 15 and 16, respectively) [46].

Reaction between N-substituted imidazole derivatives 33 or 36 with palladium sources (palladium chloride, palladium acetate or potassium tetrachloropalladate) in organic solvents (THF, EtOH, or

MeCN) afforded the corresponding palladium–imidazole com-plexes 35 and 37 as shown in Scheme (18) and (19) [47].

The complex 37 for e.g., exhibited superb catalytic activity in the reaction of Suzuki–Miyaura under conservative conditions in a non-toxic, isopropanol–water solvent (Table 8). Excellent yields of cross-coupling products 5 were obtained when 4-bromotoluene and 4-bromoanisole were used as substrates with phenylboronic acid 8 (Scheme 20). The synthesized catalysts 35 and 37 showed much lower catalytic activity when 4-vinylphenylboronic acid was used instead of phenylboronic acid [47].

Imidazole incorporated in a siloxane polymer has been used as a ligand and support for a palladium catalyst 38 by Borkowski et al as shown in Fig (2) and Scheme (21). The activity of the developed polymer-supported imidazole-based palladium catalyst 38 has been examined in catalysis of aqueous Suzuki–Miyaura cross-coupling reactions between aryl halides 3a,c and phenylboronic acid 8 using conventional heating as well as microwave irradiation (Scheme 21). The biaryls 5 were obtained in good to excellent yields in case of using aryl bromides and poor yields in case of using aryl chlorides as shown in Table (9). It was reported that the catalyst showed good recyclability under the reported mild conditions [48].

27 28 30

N

HN S

HN

OMe

MeCN

PdCl2 N

HN

S

HN

MeOPd

Cl ClMeCN/HPF6

N

N

Me

NN

S

HN

MeOPd

ClN

N

Me

29

Scheme 14. Synthesis of complex 30.

+

BOH

OH

Conditions:Cat. conc.:1.18 mol%Solvent: H2O, EtOH or iPrOHBase: K2CO3Co-catalyst:NoneTemperature: r.t. to 60 oC/ reflux (!)Time:2-12 h

3a,c

8

5

X = Br or Cl

X

R1

30

NN

S

HN

MeO PdCl

N

NMe

BOH

OHHet

HetR1

or or

R2R1

R2




Entry X R1 or HetR2

Yield %

1 Br 4-MeO C6H5- 78

2 Br 4-NO2 C6H5- 90

3 Br 4-CHO C6H5- 85

4 Br 3-NO2 4-MeC6H4- 70

5 Br 4-CHO 4-MeOC6H4- 85

6 Br 3-CHO C6H5- 73

7 Br 2-CHO C6H5- 79

8 Br 4-CN C6H5- 87

9 Br 4-MeO 4-MeOC6H4- 88

10 Br 3-NO2 4-MeOC6H4- 84

11 Br H 4-MeOC6H4- 8

12 Br 4-NO2 4-MeOC6H4- 87

13 Br H 3-MeOC6H4- 78

14 Br H 4-MeCOC6H4 75

15 Br 4-MeO 3-Thienyl 65

16 Br 3-NO2 4-F trace

17 Br 4-NO2 4-MeCOC6H4 80

18 Cl 4-MeO C6H5- trace

19 Cl 4-MeO 4-MeOC6H4- 60

20 Cl 4-MeO C6H5- 50

21 Cl 4-NO2 C6H5- 15

NN

NNPd

Cl

Cl

NNPdCl2

THF, 60 oC

31 32

Scheme 16. Synthesis of 1-trityl-1H-imidazole-based palladium complex 32.

Conditions:Cat. conc.:1 mol%Solvent: H2O/iPrOHBase: KOHCo-catalyst: noneTemperature: rt.Time:1 h

+ BOH

OH

3c X = Cl, or 13, Z = N, R = H, X = Cl

8

Z

X

ZR1R1R2 R2

NN

Tr

NN

TrPd

Cl

Cl

5 or 14

32

Tr = -C(Ph)3 Scheme 17. Suzuki–Miyaura cross-coupling reaction between different aryl chloride and arylboronic acids using complex 32 as a precatalyst.


Table 7. Suzuki–Miyaura cross-coupling reaction between different aryl chloride and arylboronic acids using complex 32 as a precatalyst.

Entry R1 R2 Yield %

1 H H 99

2 H 2-Me 95

3 H 4-Me 99

4 H 4-Cl 90

5 H 4-OH 95

6 H 3-F 80

7 H 4-MeO 75

8 H 1-(4-Methylnaphthyl)- 50

9 4-Me H 95

10 2-Me H 90

11 3-Me H 90

12 2,3-Me2 H 80

13 4-F H 99

14 4-MeO H 75

15 4-Ac H 20

16 2-Pyridyl H 15

+

N

N

C3H7OH2C

C3H7OH2C

ClPd(OAc)2

THF/ 70 oC

N

N

C3H7OH2C

C3H7OH2C

N

N

CH2OC3H7

CH2OC3H7

Pd

NN

C3H7OH2C

NN

CH2OC3H7

Pd

Cl

Cl

33 34 35 Scheme 18. Synthesis of imidazole-based palladium complex 35.

N

N

C3H7OH2CCl K2PdCl4

MeCN/ toluene 130 oC

NN

NNPd

Cl

Cl

36 37 Scheme 19. Synthesis of imidazole-based palladium complex 37.

Conditions:Cat. conc.: 0.00001 mol%Solvent: H2O/ iPrOH Base: KOHCo-catalyst: noneTemperature: 60 oC

+ BOH

OH

3a 5

Br

8

NN

NNPd

Cl

Cl

R2 R2

R1 R1

37

Scheme 20. Suzuki–Miyaura cross-coupling reaction between different aryl bromides and arylboronic acids using complex 37 as a precatalyst.


Table 8. Suzuki–Miyaura cross-coupling reaction between different aryl bromides and boronic acids using complex 37 as a precatalyst.

Entry R1 R2 Yield %

1 2-Me H 100

2 2-Me 4-vinyl 34

3 4-Me H 100

4 4-MeO H 100

BuSi

OSi

OSi

OSi

n

N

N

PdClCl

BuSi

OSi

OSi

OSi

n

N

N

38

Fig. (2). Representation of polymer-supported imidazole-based palladium catalyst 38.

2.3. Five-Membered with Three Heteroatom Heterocycles-Based Palladium Complexes

2.3.1. Triazole-based Palladium Complexes

2.3.1.1. 1,2,3-Triazole-based Palladium Complexes

New ligands including substituted triazolylisoxazole 39 were synthesized by means of click-chemistry procedures reported by Nikolay et al. The obtained ligands 39 was used in the preparation of palladium(II) complexes 40. Thus, the reaction of ligands 39 with sodium tetrachloropalladate in methanol afforded the corre-sponding water and air-stable palladium complex 40 in good yield (Scheme 22) [49].

The catalytic activity of the novel palladium complexes 40 in aqueous cross-coupling reactions has been examined for the Su-zuki-Miyaura cross-coupling reactions of 3-halobenzoic acid 3a,b with 4-methoxyphenylboronic acid 8 under air atmosphere (Scheme 23). It was found that the reaction proceeded smoothly at mild tem-perature and in short time giving a high yield of cross-coupling product 5 without any inert gas protection in the presence of tested complexes 40 (Scheme 23) [49].

1H-1,2,3-Triazole-based palladium complexes 42a,b have been synthesized by reacting (CH3CN)2PdCl2 with the ‘Click’ created ligands 41a,b namely, 1-(2,6-diisopropylphenyl)-4-(phenylthio/ selenomethyl)-1H-1,2,3-triazole (Scheme 24) [50].

BuSi

OSi

OSi O

Si

n

N

N

PdCl Cl

BuSi

OSi

OSi

OSi

n

N

N

Conditions:Solvent: H2O/2-propanolBase: K2CO3Co-catalyst: noneTemperature: 60-100 oCTime:30 min-3 h ! or 1h µw

+ BOH

OH

3a,c 8a

X

RR

38

5

Scheme 21. Suzuki–Miyaura cross-coupling reaction between different aryl bromide and boronic acids using complex 38 as a precatalyst.


Table 9. Suzuki–Miyaura cross-coupling reaction between different aryl bromide and boronic acids using complex 38 as a precatalyst.

Entry X R Yield %

1 Br 2-Me 100

2 Br 4-Me 100

3 Br 2-MeO 97

4 Br 4-CHO 45

5 Br 2-Ac 13

6 Cl 4-Cl 10

7 Cl 4-NO2 16

NO

N

Ar

NN

R

N

O

N

Ar

NN

R

Pd

Pd Cl

Cl

Cl

ClNa2PdCl4

MeOHNO N

Ar

NN

R

2

39 40

Ar = C6H5, 4-MeC6H4-

R = CH2-OH, CH-OiPr, C6H5-

Scheme 22. Synthesis of imidazole-based palladium complex 40.

+ BOH

OH Conditions:Cat. conc.:0.1 mol%Solvent: H2O/MeOHBase: K2CO3Co-catalyst:NoneTemperature:20-100 oC/ reflux (!)Time: 5 min-4 h

3a,b, R1 = 3-COOH

8R2 = 4-MeO

X

5

HOOCMeO OMe

HOOC

Yield = 89-100 %

NO

N

Ar

NN

R

NO

N

Ar

NN

R

Pd

Pd Cl

Cl

Cl

Cl

40

Scheme 23. Suzuki–Miyaura cross-coupling reaction between different 3-halobenzoic acid 3a,b with 4-methoxyphenylboronic acid 8 using complex 40 as a precatalyst.

N

NN

Y

41, Y = S, Se

PdCl2(MeCN)2

MeCN/ rt./ 5 h

N

NN

Y

42, Y = S, Se

Pd

Cl

Cl

Scheme 24. Synthesis of 1H-1,2,3-triazole-based palladium complexes 42a,b.


Conditions:Cat. conc.:0.01-1 mol%Solvent: H2OBase: K2CO3Co-catalyst: noneTemperature: 100 oCTime:30 min-12 h

+ BOH

OH

3a 8

Br

RR

N

NN

Y

Cat 42a: Y = S, Cat 42b: Y = Se

Pd

Cl

Cl

5

42a,b

Scheme 25. Suzuki–Miyaura cross-coupling reaction between substituted aryl bromides 3a and phenylboronic acid 8 using complex 42 as a precatalyst.

Table 10. Suzuki–Miyaura cross-coupling reaction between different aryl bromide and phenylboronic acids using complex 42 as a precatalyst.

Yield % Entry R

Cat 42a Cat 42b

1 4-CHO 91 99

2 4-CN 62 52

3 4-NO2 93 89

4 4-Ac 90 86

5 4-COOH 88 93

6 4-Me 52 42

7 4-MeO 93 36

The triazole-based palladium complexes 42a,b have efficiently

catalysed a homogenous Suzuki–Miyuara cross-coupling of substituted aryl bromides 3a and phenylboronic acid 8 in an aqueous medium (Scheme 25). A catalyst loading of 0.01–0.1 mol% is optimum for successful cross-couplings with variable yield percent- ages. Activated aryl bromides gave good conversion when Suzuki– Miyaura cross-coupling was carried out for 1–2 h in the presence of catalyst 42a, however, the reaction time increased when catalyst 42b was used for the same substrate (Table 10, entries 3-6) [50].

Palladium immobilized triazole-functionalized siloxanes 43 and 44 reacted with palladium acetate to afford the corresponding recyclable palladium catalysts 45 and 46 as shown in Scheme (26) [51].

The catalytic activity of both catalysts, 45 and 46, were tested in the Suzuki–Miyuara cross-coupling reaction of 2-bromotoluene 3a and phenylboronic acid 8a at 60 oC in a 2-propanol/water mix-ture (Scheme 27). It was found that 100% conversion of 2-bromotoluene was obtained after 1 h. It was found that, nine subse-

quent cycles were successfully performed efficiently with the same catalyst 45 [51].

A novel 1,2,3-triazole ligand 47 functionalized with a hydro-philic group has been synthesized by the treatment of 1-‐chloro-‐4-‐bromobutane with sodium azide in H2O/MeOH at 80 °C overnight, followed by 1,3-‐dipolar cycloaddition with 2-‐ethynylpyridine under standard click reaction conditions. Quar-ternization of ligand 47 with an excess of a 30 % aqueous solu-tion of Me3N in MeCN produced ionic chelating ligand 48 (Scheme 28). The reaction of ligand 48 with an equimolar amount of [Pd(cod)Cl2] in dichloromethane/methanol afforded the correspond-ing stable water-soluble palladium complex 49 in almost quantita-tive yield [52].

Catalysis of the Suzuki–Miyaura cross-coupling reaction be-tween aryl or heteroaryl halides 3a,c and aryl boronic acids 8 was examined using the water soluble palladium complex 49 in clean water (Scheme 29). As shown in Table (11), the reaction between aryl halides 3a,c and aryl boronic acids 8 gave the cross-coupled


Pd(OAc)2

BuSi

OSi

OSi

OSi

n

N N

N

BuSi

OSi

OSi

OSi

n

N N

N

43 44

BuSi

OSi

OSi

OSi

n

N N

N

RPd

AcO

O

O

Bu SiO Si

O SiO Si

n

N NN

R

Pd

OAc

OAc

BuSiOSi

OSiOSi n

NNN

R

4546

Scheme 26. Synthesis of Pd(II) catalysts 45 and 46.

Conditions:Cat. conc.:0.1 mmolSolvent: H2O/ iPrOHBase: KOHCo-catalyst: noneTemperature: 60 oCTime: 1 h

+ BOH

OH

3a

Br

8a 5

47 or 48

Yield = 99% (Pd/A 0.0010 g copolymer)Yield = 100% (Pd/B 0.0014 g copolymer)

R1 = 2-Me

Scheme 27. Suzuki–Miyaura cross-coupling reaction between 2-bromotoluene 3a and phenylboronic acid 8a using complexes 45 or 46 as a precatalyst.

N

N

NN

Cl

N

N

NN

N

MeCN/ D

Me3N

Cl

[Pd(cod)Cl2]

DCM/ MeOH, rt.

N

N

NN

N Cl

Pd

Cl

Cl

47 48 49 Scheme 28. Synthesis of complex 49.


Conditions:Cat. conc.:0.01-0.1 mol%Solvent: H2OBase: K2CO3Co-catalyst: TBABTemperature: 120 oCTime: 30 min-5 h

+ BOH

OH

3a,c 8

X

R1R1R2 R2

N

N

NN

N Cl

Pd

Cl

Cl

5

49




1 Br 4-Ac H 96

2 Br 4-NO2 H 93

3 Br 4-CN H 93

4 Br 4-MeO H 97

5 Br 4-Me H 89

6 Br 3-Me H 85

7 Br 2-Me H 84

8 Br 2-Thienyl H 96

9 Br 3-Pyridyl H 73

10 Br 4-Ac 4-F 98

11 Br 4-Ac 4-MeO 98

12 Br 4-Ac 4-Me 97

13 Br 4-Ac 2-Me 95

14 Br 4-Ac 3-Me 95

15 Cl 4-Ac H 80

16 Cl 4-CN H 93

17 Cl 4-NO2 H 100

18 Cl 4-NO2 2-Me 98

19 Cl 4-NO2 3-Me 97

20 Cl 4-NO2 4-Me 93

21 Cl 4-NO2 4-F 89

products 5 in good to excellent yields, using TBAB as a co-catalyst. It was reported that palladium NPs were formed after the catalytic

reactions, in which the ionic ligand served as a stabilizer of the NPs [52].


Catalyst 49 reusability has been examined for the reaction be-tween 4-bromoacetophenone 3a and phenylboronic acid 8. When the reaction was finished, the residual aqueous solution was re-charged with the same substrates and one equivalent of the base for the next run. The catalytic solution containing the palladium species was used four times; a slight loss of catalytic activity was observed.

2.3.1.2. 1,2,4-Triazole-based Palladium Complexes Treatment of chloromethylated polystyrene (cross-linked with 2

divinylbenzene), with 1-amino-3-methyl-5-mercaptotriazole 50 in dimethylformamide afforded the novel polystyrene-bound triazole 51 as shown in Scheme 30. The 1,2,4-triazole-functionalized poly-

PdCl2(PhCN)2

EtOH/ D 15 hNN

NMe

SH

PdNH2

Cl

NN

NMe

S

NH2

NN

NMe

S

H2N

DMF/ 100 oC

24 h

Cl

Cl50 51 52


Pd

Conditions:Cat. conc.:0.001 mol%Solvent: H2OBase: K2CO3Co-catalyst: noneTemperature: 70 oCTime:10 h

+ BOH

OH

3a,b 8a

X

RR

5

NN

NMe

S

H2N Cl

Cl

52

Scheme 31. Suzuki–Miyaura cross-coupling reaction between different aryl iodides and aryl bromides and phenylboronic acids using complex 52 as a precata-lyst.

Table 12. Suzuki–Miyaura cross-coupling reaction between different aryl iodides and aryl bromides and phenylboronic acids using complex 52 as a precatalyst.

Entry X R Yield % TON

1 I H 99 990

2 I 3-NO2 99 990

3 I 4-NO2 99 990

4 I 4-Ac 99 990

5 I 4-Cl 97 970

6 I 4-Br 96 960

7 I 4-MeO 96 960

8 Br H 98 980

9 Br 3-NO2 99 990

10 Br 4-NO2 99 990

11 Br 4-CN 98 980

12 Br 4-CHO 98 980

13 Br 4-Cl 97 970

14 Br 4-MeO 95 950


styrene resin-supported Pd(II) complex 52 was prepared by stirring a suspension of 1,2,4-triazole-functionalized polystyrene resin 51 in a solution of PdCl2(PhCN)2 in refluxing ethanol for 15 h (Scheme 30) [53].

Excellent catalytic activity for the palladium catalyzed Suzuki–Miyaura cross-coupling reaction of aryl iodides 3b and aryl bro-mides 3a with phenylboronic acid 8a was observed in water when the novel polystyrene-bound triazole palladium complex 52 was used as a precatalyst as shown in Scheme (31) and Table (12). The catalyst 52 used is easily separated and can be reused for several times without any noticeable change in its activity [53].

2.3.2. 1,2,4-Oxadiazole-based Palladium Complexes

Treatment of nitriles with two equivalents of pyrroline-N-oxide 53 and one equivalent of PdCl2 afforded the corresponding fused bicyclic 1,2,4-oxadiazoline palladium(II) complexes 54 as shown in Scheme 32. Refluxing 1,2,4-oxadiazoline palladium(II) complexes

54 in chloroform for one week produced the new ketamine palla-dium(II) complex 55 (Scheme 32) [54].

Immobilization of the synthesized complexes 54 and 55 on the chitosan membrane to give the new heterogenized palladium(II) catalysts 56 and 57 has been achieved via replacement of oxadia-zoline or benzamide-type ligands by an amine group of the mem-brane (Fig. 3) [54].

The heterogenized catalysts 56 and 57 have been used for the microwave-assisted Suzuki–Miyaura cross-coupling in water. The catalytic activity of the prepared catalysts 56 and 57 in Suzuki–Miyaura cross-coupling reactions in water using p-bromoanisole 3a and phenylboronic acid 8a was successful to give p-methoxybi-phenyl 5 in excellent yield. The effects of catalyst loading, tempera-ture, time, and base were investigated, and the best results were obtained using the conditions as shown in Scheme (33). It should be noted that the supported catalysts 56 and 57 were recovered and reused up to seven times, with a gradual loss of their catalytic activ-ity [54].

R CN

N

O

PdCl2

Acetone/ rt. 12 hN

ON

R

Pd

Cl

Cl

N

O N

RNH

ONPd

Cl

Cl

HN

O NCHCl3/ !

R = 4-Cl-C6H4

53 54 55

Cl

Cl

Scheme 32. Synthesis of complexes 54 and 55.

O

OHO

H

NHO

HOO

HO

H

NH2

O

HO

O

HO

H

NH2O

HO

O Pd ClCl

N O

N

56

O

OHO

H

NHO

HOO

HO

H

NH2

O

HO

O

HO

H

NH2O

HO

O Pd ClCl

NHO

N Cl

57

Fig. (3). Representation of the structures of the two complexes 56 and 57.


3. SIX MEMBERED HETEROCYCLES-BASED PALLA-DIUM COMPLEXES

3.1. Six-membered with One Heteroatom Heterocycles-based Palladium Complexes

3.1.1. Pyridine-based Palladium Complexes

New type of palladium(II)-complex 61 has been reported by Althagafi et al. 2-Aminopyridine 58 was treated with dimethylfor-mamide dimethylacetal 59 in benzene, to afford the formamidine derivative 60 as shown in Scheme (34). The Pd(II)-complex 61 was prepared by dissolving the formamidine derivative in methanol followed by addition of an equimolar amount of sodium tetrachlo-ropalladate, at room temperature (Scheme 34) [33].

Suzuki–Miyaura cross-coupling of aryl halides 3a,c with aryl boronic acids 8 using new palladium complex 61 as a precatalyst was investigated. A pyridine-based Pd(II)-complex 61 was used in open air under thermal as well as micro-wave irradiation condi-

tions, using water as an eco-friendly green solvent (Scheme 35, Table 13) [33].

A series of water-soluble cationic pyridine based palladium(II) SNS pincer complexes 64 and 65 have been successfully synthe-sized by reaction of 2,6-bis(alkylthio or arylthiomethyl)pyridine 62 or 63 with PdCl2(MeCN)2 , followed by treatment with the halide abstractor AgOTf to provide the desired SNS-Pd(II) complexes 64 in good yield (Scheme 36) [55].

The potentiality of the synthesized pyridine-based SNS-palladium(II) complexes 64 has been examined for Suzuki–Miyaura cross-coupling reactions. A detailed investigation into the applica-tion of these complexes 64 in the Suzuki–Miyaura cross-coupling reaction was conducted using various aryl bromides or chlorides 3a,c and arylboronic acids 8 as coupling components in water. All the complexes showed high catalytic activity in Suzuki–Miyaura coupling reaction to provide the corresponding biaryls 5 in good to excellent yields with only 0.5 mol % catalyst loading (Scheme 37, Table 14) [55].

Conditions:Cat. conc.: 0.00014-0.00017 mol%Solvent: H2O Base: K2CO3Co-catalyst: noneTemperature: 160 oCTime: 15 min

+ BOH

OH

3a 5

Br56 or 57

8a

MeO MeO

Using 58:Yield = 100%Using 59:Yield = 95%

R1 = 4-MeO

Scheme 33. Suzuki–Miyaura cross-coupling reaction between p-bromoanisole and phenylboronic acids using complexes 56 or 57 as a precatalyst.

N NMe

MeOMe

MeO

58 59 60

NH2 N N NMe

Me

Benzene Na2PdCl4 MeOH/ r.t.

61

N N

HNPd

Me Me

Cl

Cl!


61

N N

HNPd

Me Me

Cl

Cl

+ Ar-BOH

OHConditions:Cat. conc.:0.25 mol%Solvent: H2OBase: KOHCo-catalyst:TBABTemperature:100 oC/ reflux (!) or 110 oC/µwTime: 3 h(!) or 10 min µw

3a,c 8

X

R

Ar

5

R




Entry X R Ar Δ Yield % µW Yield %

1 Br H C6H5 78 92

2 Br 2-COCH3 C6H5 61 93

3 Br 4-OCH3 C6H5 70 90

4 Br 4-COOH C6H5 74 89

5 Br 4-CH3 C6H5 24 60

6 Br 4-OH C6H5 77 87

7 Cl H C6H5 - 90

8 Cl 4-OH C6H5 - 82

9 Cl 3-NH2 C6H5 - 74

10 Br 2-Thienyl C6H5 - 47

11 Br 2-Ac 4-CH3C6H4 90 97

12 Br 2-Ac 4-ClC6H4 93 94

13 Br 2-Ac 4-FC6H4 82 90

14 Br 2-Ac 3-NH2C6H4 76 96

15 Br 2-Ac 2,4,6-(CH3)3C6H2 83 90

62

63

65

N

SSRR

PdCl2(MeCN)2

DCM, rt, 24 h

PdCl2(MeCN)2

DCM, rt, 24 h

N

SSRR Pd

Cl Cl

R = C6H5 or 4-BrC6H4

R = s-Bu or 4-tBuC6H4

N

SSRR Pd

Cl

Cl

N

SSRR Pd

Cl

OTfPdCl2(MeCN)2

MeOH, rt, 24 h

64

R = C6H5 or 4-BrC6H4



+ Ar-BOH

OH Conditions:Cat. conc.:0.5 mol%Solvent: H2OBase: KOHCo-catalyst:TBABTemperature:120 oC/ reflux (!)Time: 2 h

3a,c 8

N

SSRR Pd

Cl

OTf

64

X

R

Ar

5

R

Scheme 37. Suzuki–Miyaura cross-‐coupling reaction between different aryl halides and arylboronic acids using complexes 64 as a precatalyst. Table 14. Suzuki–Miyaura cross‑coupling reaction between different aryl halides and arylboronic acids using complexes 64 as a precatalyst.

Entry X R Ar Yield %

1 Br 4-MeO 4-BrC6H4- 88

2 Br 4-MeOC6H4- 4-ClC6H4- 90

3 Br 4-MeOC6H4- 3,5-(MeO)2C6H3- 86

4 Br 4-MeOC6H4- 4-CHOC6H4- 86

5 Br 4-MeOC6H4- 3-NO2C6H4- 81

6 Br 4-MeCOC6H4- C6H5- 91

7 Br 4-NH2C6H4- C6H5- 82

8 Br 4-MeC6H4- C6H5- 88

9 Br 2-NO2-4-MeOC6H3- C6H5- 81

10 Br 4-MeOC6H4- 4-MeC6H4- 89

11 Br 4-MeOC6H4- 4-iPrC6H4- 86

12 Cl 2-CNC6H4- C6H5- 77

13 Cl 2-CNC6H4- 4-MeC6H4- 81

+ BOH

OHConditions:Solvent: H2OBase: K2CO3Co-catalyst:noneTemperature:r.t.

3a-c 8

X

R

Ar

5

R

NNH2H2N

Pd

O

H2O ON

O

O

Ar 66

Scheme 38. Suzuki–Miyaura cross�coupling reaction between different aryl halides and arylboronic acids using complexes 66 as a precatalyst.

A supramolecular N,N',O-tridentate ligand was synthesized by the inclusion of 2,6-diaminopyridine in the hydrophobic β-CD cav-ity of the ionic liquid which gave a new air-stable, highly water-soluble palladium complex 66, that was used as a catalyst for green

Suzuki cross-coupling reactions in water at ambient temperature with good to excellent yields, as depicted in (Scheme 38, Table 15). The catalyst can be removed and recycled [56].


The pyridine-based NNN pincer ligands 67 have been synthe-sized by the reaction of pyridine-2,6-dicarbonyldichloride and ben-zylamine derivatives in the presence of 4-dimethylaminopyridine (DMAP). The reaction of ligands 67 with palladium acetate in ace-tonitrile afforded the corresponding palladium pincer complexes 68 (Scheme 39) [57].

All the complexes 68 were examined as catalysts in the Suzuki-Miyaura cross-coupling reaction of phenylboronic acid 8 and aryl halides 3a,b in ethanol/water mixture (Scheme 40, Table 16). A comparison study between the synthesized phosphine free com-plexes and the corresponding phosphine ligands hasbeen done and showed that the reactivity of the acetonitrile complex 68 was not

Table 15. Suzuki–Miyaura cross-coupling reaction between different aryl halides and arylboronic acids using complexes 66 as a precatalyst.


1 Cl H C6H5 71

2 Br H C6H5 75

3 I H C6H5 84

4 I 4-Me C6H5 72

5 I 4-NO2 C6H5 87

6 Br 4-Me C6H5 69

7 Br 4-NO2 C6H5 76

8 Cl 4-Me C6H5 65

9 Cl 4-NO2 C6H5 73

10 Cl H 3,4,5-(OCH3)3C6H2 72

11 Br H 3,4,5-(OCH3)3C6H2 74

12 I H 3,4,5-(OCH3)3C6H2 77

13 I 4-MeO C6H5 86

14 Br 2-Me C6H5 66

15 Br 2,6-Me2 C6H5 58

N

NNPd

68

OO

RR

N

CMe

Pd(OAc)2

MeCN

N

HNNH

67

OO

RR

R = H, Me, OMe, Cl Scheme 39. Synthesis of complexes 68.

+

Conditions:Cat. conc.:0.005 mmolSolvent: H2O/EtOHBase: K2CO3Co-catalyst:noneTemperature:82 oC/ reflux (!)Time: 4-24 h

3a,b

N

NNPd

68Ar X

Ar

5

OO

RR

N

CMe

BOH

OH

8a

Scheme 40. Suzuki–Miyaura cross-coupling reaction between different aryl halides and phenylboronic acids using complexes 68 as a precatalyst.


inferior to triphenylphosphine counterpart under the given condi-tions. Therefore, acetonitrile complexes of pyridine-based palla-dium 68 may be considered as an alternative for phosphine com-plexes in Suzuki-Miyaura cross-coupling [57].

Sulfonated pyridyl imine-based ligands 69 and their Pd(II) complexes 70 have been successfully synthesized by Hanhan et al. via treating the ligands 69 with PdCl2(MeCN)2 as shown in Scheme (41). These ionic pyridyl imine-based Pd(II) complexes 70 showed

Table 16. Suzuki–Miyaura cross-coupling reaction between different aryl halides and phenylboronic acids using complexes 68 as a precatalyst.

Entry X Ar Yield %a

1 Br 2-CHOC6H4- 89

2 Br 4-MeCOC6H4- 99

3 Br Isatin-5-yl 25

4 Br 2,4,6-Me3C6H2- 75

5 Br 4-IC6H5- 73

6 Br 4-COOHC6H4- 95

7 Br 4-CF3OC6H4- 72

8 Br 4-CHOC6H4- 93

9 I 4-CHOC6H4- 97

10 I 1-Naphthyl 90

11 Br C6H5- 89

12 Br 4-MeC6H4- 95

13 I C6H5- 98

14 Br Phenacyl 51

15 Br 4-C6H5CO-C6H4- 97

16 Br 2-COOHC6H4- 76

a GC yield%

RO3S

R1

N

R1R2

N SO3R

R1

N

R1R2

N

Pd

ClCl

PdCl2(MeCN)2

R = Na, NBu4, BmimR1 =H, Me, iPrR2 = H, Me

69 70

Scheme 41. Synthesis of complexes 70.

Conditions:Cat. conc.:0.1 mol%Solvent: H2OBase: K2CO3Co-catalyst:TBABTemperature:80 oC/850 w µw or reflux (!)Time: 5 min (µw), 2 h (!)

70+ BOH

OH

3a,c 8

X

R2R1R1

SO3R

R1

N

R1R2

N

Pd

ClCl

R2

5

Scheme 42. Suzuki–Miyaura cross-coupling reaction between different aryl halides and arylboronic acids using complexes 70 as a precatalyst.


high efficiency in the catalysis of Suzuki-Miyaura cross-coupling reaction in water for SMC reactions in the presence of potassium carbonate as a base and tertabutylammonium bromide (TBAB) as the phase transfer reagent (Scheme 42) [58].

It was found that by using the optimized conditions and 0.1 mol % of pyridyl imine-based palladium complexes 70, cross-coupling between various aryl halides 3a,c and aryl boronic acid 8 was suc-cessful, and good to excellent yields (with aryl bromides) were obtained in most of the cases under microwaves irradiation (Table 17) [58].

In general, aryl bromides 3a showed good results (72%–98% yields) using the pyridyl imine-based palladium complexes 70 as precatalysts compared with the aryl chlorides 3c (Table 17). Fur-thermore, Catalyst recyclability could be obtained for up to four cycles before the decomposition of the catalyst under the influence of microwaves [58].

O-carboxymethyl chitosan Schiff base 71 has been synthesized by the treatment of (E)-2-((4-isopropylphenyl)imino)-1,2-di(pyridin-2-yl)ethanone with chitosan for 72 h, and then ethanol solution of monochloroacetic was added to afford the support mate-

Table 17. Suzuki–Miyaura cross-coupling reaction between different aryl halides and arylboronic acids using complexes 70 as a precatalyst.

Δ Yield %a µW Yield %a Entry X R1 R2

Cat 70a Cat 70b Cat 70a Cat 70b

1 Br H H 96 91 98 93

2 Br 4-Me H 90 88 97 91

3 Br 2-Me H 87 84 96 92

4 Br 4-COMe H 84 81 93 89

5 Br 4-OMe H 91 88 94 92

6 Br 2,6-Me2 H 69 66 78 72

7 Br 4-NO2 H 83 77 93 96

8 Br 4-Me 4-Me 87 82 94 92

9 Br 2-Me 4-Me 85 79 92 91

10 Br 4-OMe 4-Cl 79 72 94 89

11 Br 4-OH H 82 78 96 94

12 Br 4-COOH H 84 79 92 92

13 Br 4-COOH 4-Me 87 82 95 91

14 Br 4-OH 4-Me 81 73 94 90

15 Br 4-COOH 4-F 84 79 97 91

16 Br 4-OH 4-F 89 81 91 88

17 Cl 4-NO2 H 7 5 14 11

18 Cl H H 9 7 16 13

19 Cl 4-Me H 8 5 8 8 a GC yield%

OH

H

NH

OH O

n

N

N

N

NaPdCl4/ H2O

OH

H

N

OH O

n

N

N

NPd

Cl

Cl

71 72

O

HOOC

O

HOOC



rial like pendant to the Schiff base. Treatment of the latter support 71 with sodium tetrachloropalladate in water afforded the corre-sponding biopolymer supported palladium(II) complex 72 as shown in Scheme (43) [59].

The catalytic efficiency in Suzuki cross-coupling reactions was evaluated for the developed catalyst 72 under solvent-free condi-tions (Scheme 44). Variable catalytic activity for Suzuki–Miyuara cross-coupling reaction of aryl bromides 3a and iodides 3b with phenylboronic acid 8 was observed when the novel palladium com-plex 72 was used as a precatalyst as shown in Table (18). The cata-lyst 72 showed low efficiency in case of cross-coupling of aryl chlorides 3c with phenylboronic acid 8. The reusability of the de-veloped catalyst 72 showed that the catalyst was recyclable and recoverable several times [59].

Phosphine-‐free new palladium(II) complexes 74a-c of 2,6-‐bis(pyrrolyl)pyridine based pincer ligands 73 have been synthe-sized by Stetter condensation of 2,6-‐pyridinedicarboxaldehyde and the corresponding chalcones followed by cyclization in the pres-ence of ammonium acetate. Palladium complexes 74a-c of the syn-thesized pincer ligands were prepared by the reaction of 73 with palladium acetate in acetonitrile as a shown in Scheme (45) [60].

The catalytic activities of the palladium complexes 74a-c for Suzuki-Miyaura cross-coupling reaction were examined under mild reaction conditions using water as a solvent. 4-‐Bromoacetophenone 3a and phenylboronic acid 8a were selected as model substrates as shown in Scheme (46). The effects of both base and solvents have been investigated to attain the optimized conditions which then have been applied for various derivatives of aryl bromides 3a

Conditions:Cat. conc.:0.006 mol%Solvent: solvent freeBase: K2CO3Co-catalyst: noneTemperature:50 oC/ µwTime: 5 min

+ BOH

OH

3a-c 8a

X

RR

OH

HH

N

OH

O

O

n

N

N

NPd

Cl

Cl

72

5

COOH

Scheme 44. Suzuki–Miyaura cross-coupling reaction between different aryl halides and phenylboronic acids using complex 72 as a precatalyst.

Table 18. Suzuki–Miyaura cross‑coupling reaction between different aryl halides and phenylboronic acids using complex 72 as a precatalyst.

Entry X R Yield % TON TOF (h-1)

1 Br 2-MeO 78 13000 162500

2 Br 3-MeO 96 16000 200000

3 Br 4-MeO 97 16167 202087

4 Br 3-NO2 90 15000 187500

5 Br 4-NO2 91 15167 189597

6 Br 3-Me 38 6333 79162

7 Br 4-Me 55 9167 114587

8 I 4-MeO 83 13833 172912

9 I 3-No2 73 12167 152087

10 I 4-Me 38 6333 79162

11 Cl 4-MeO 55 9167 114587

12 Cl 3-NO2 60 10000 125000

13 Cl 4-Me 25 4167 52087


(Table 19). Coupling reactions were successful with aryl bromides 3a having both electron-donating and withdrawing substituents with good to excellent yields [60].

Treatment of 2,6-dibromoisonicotinic acid 75 with ethyl 4-(1H-imidazol-1-yl)butanoate 76 provided intermediate imidazolium salt

77, which was palladated with palladium acetate in dimethyl sul-foxide to afford the corresponding imidazole-based palladium com-plex 78a (Scheme 47). Under the acidic reaction conditions, hy-drolysis occurred to afford the tricarboxylic pincer complex 78b (Scheme 47) [61].

N

HNNH

R''R''

R'R'

Pd(OAc)2/ MeCN/ !N

NN

R''R''

R'R'

Pd

Me

C

N

74a, R' = H, R'' = OMe74b, R' = OMe, R'' = OMe74c, R' = R'' = Cl

7374a-c

Scheme 45. Synthesis of complexes 74a-c.

+ BOH

OH Conditions:Cat. conc.:0.05-0.75 mol%Solvent: H2O/EtOHBase: K2CO3Co-catalyst:NoneTemperature:85 oC/ reflux (!)Time: 2 h

3a 8a

Br

R

5

R

NNN

R''R''

R'R'

Pd

MeCN

74a-c

Scheme 46. Suzuki–Miyaura cross-‐coupling reaction between different aryl bromides and phenylboronic acids using complexes 74a-c as a precatalyst. Table 19. Selected results of Suzuki-‐Miyaura cross-‐coupling reaction catalyzed by 74a, 74b, and 73ca.

Entry R Yield %a

(74a) Yield %a,b

(74b) Yield %a

(74c)

1 4-CHOC6H4- 98 99 (96) 98

2 4-MeCOC6H4- 99 99 (97) 99

3 4-MeOC6H4- 98 96 (93) 91

4 4-MeC6H4- 98 97 (95) 87

5 C6H4- 99 99 (97) 98

6 4-NO2C6H4- 99 98 (91) 99

7 4-ClC6H4- 99 98 (94) 98

8 2-FC6H4- 99 92 (87) 98

aYields (%) were determined by GC, bIsolated yields in parentheses


sealed tube 24 h, 150 oC

N

N N

COOH

N

N

N

N

Br

Pd(AcO)2

DMSO

N

COOH

N

N

N

N

Pd

Br

Br

N

COOH

Br Br

COOEt

COOEtEtOOC

Br

COORROOC

R = a, Et, b, H

75

76

77 78

Scheme 47. Synthesis of complexes 78a,b.

Conditions:Cat. conc.: 0.01 mol%Solvent: H2O Base: K2CO3Co-catalyst: noneTemperature: 100 oCTime: 2 h

+ BOH

OH

3a 8

Br

R1R1R2 R2

5

N

COOH

N

NN

N

Pd

Br

COORROOC

R = Et, H

Br

78

Scheme 48. Suzuki-‐Miyaura cross-‐coupling reaction of aryl bromide and arylboronic acid using complexes 78a, and 78b as precatalyst. Table 20. Suzuki-‐Miyaura cross-‐coupling reaction of aryl bromide and arylboronic acid using complexes 78a, and 78b as precatalyst.

Entry R1 R2 Yield %

Cat 78a Yield %

Cat 78b

1 4-Ac H 99 99

2 4-Ac 4-MeO 99 99

3 4-Ac 1-Naphthyl 99 99

4 4-NO2 H 99 99

5 4-NO2 4-MeO 99 99

6 4-CN H 99 99

7 4-CN 4-MeO 94 99

8 4-CN 1-Naphthyl 99 99

9 4-MeO H 24 87

10 4-MeO 4-MeO 91 50

11 4-MeO 1-Naphthyl 99 88

12 3-MeO H 82 88

13 3-MeO 4-MeO 41 99

14 3-MeO 1-Naphthyl 99 71

15 4-Me H 35 69

16 4-Me 4-MeO 74 82

17 1-Naphthyl 4-MeO 68 76

18 1-Naphthyl 1-Naphthyl 99 99


N

HN

N

Br

N

N

N

Br

NN

N

Br

N

N

N

Br

NN

N

Br

N N

N

NN

N

Br

Br

NNN

NN N

Br

Br

NN

NNN

N

Br

Br

N

N

N

PdCl2(MeCN)2

N2/ THF

N

N

N

N

N

N

PdCl2(MeCN)2 N2/ THF

PdCl2(MeCN)2

N2/ THF

NN

N

NN

N

N N

N

NN

N

PdCl2(MeCN)2 N2/ THFNNN

NN N

NN

NNN

N

N

N

N

PdCl2(MeCN)2

PdCl2(MeCN)2 N2/ THF

N2/ THF

Pd

Pd

Cl

Cl

PdCl Cl

Pd

Cl

Cl

Pd

Cl

Cl

Pd

Cl

Cl

Pd

Cl

Cl

Pd

Cl

Cl

Pd

Cl

Cl

PdCl Cl

Pd

Cl

Cl

ClCl

79

80

81

82

83

84

85

86

87

88

8990

91

92

93

94

95

96

97

Scheme 49. Synthesis of the palladium complexes 82, 85, 88, 91, 94, and 97.

The catalytic activity of both palladacycles 78a and 78b, was evaluated with Suzuki–Miyaura cross-coupling in an aqueous me-dium (Scheme 48). Thus, by using complexes 78a and 78b, various arylboronic acids 8 reacted with aryl bromides 3a, providing good to excellent yields of the cross-coupled products 5, regardless of the electronic or steric nature of the coupling partners. In general, pal-

ladium complex 78a, showed better catalytic activity than complex 78b, except in a few couplings (entries 10, 11 and 14), probably due to the higher hydrophilicity that confers a remarkable stability to the latter complex in the reaction conditions (Table 20) [61].

A new series of 2-pyridylbenzimidazole based ligands 81, 84, 87, 90, 93, and 96 weas prepared by one-pot reaction of 2-


pyridylbenzimidazole 79 with various structurally related deriva-tives of benzyl bromide in the presence of a proper base in anhy-drous toluene or tetrahydrofuran (Scheme 49). The palladium com-plexes 82, 85, 88, 91, 94, and 97 of the prepared ligands were ob-tained by reactions of 81, 84, 87, 90, 93, and 96 with PdCl2(MeCN)2 using tetrahydrofuran as a solvent as shown in Scheme (49) [62].

The catalytic activity of synthesized pyridylbenzimidazole-based palladium complexes 82, 85, 88, 91, 94, and 97 (91 was taken as an example) was examined for the Suzuki-Miyaura cross-coupling reactions between phenylboronic acid 8a and aryl bro-mides 3a and chlorides 3c using aqueous DMF as a solvent and in the presence of Cs2CO3 as a proper base (Scheme 50). The complex 91 has been catalysed the cross-coupling of aryl bromides 3a with phenylbronic acid 8a, yielding biaryls 5 in high yields (Table 21). The lower yields were obtained in the case of aryl chlorides 3c (Table 21) [62].

The reaction of 2-‐(pyridine-‐2-‐ylmethylsulfanyl)benzoic acid 98 with an equimolar amount of [Pd(CH3CN)2Cl2] in acetonitrile re-sulted in the corresponding palladium complexes 99 (in low yield) and the unexpected complex 100 (Scheme 51). The complex 99 was found to be soluble and stable in water more than 100 [63].

The application of complex 99 in the catalysis of Suzuki-Miyaura cross-coupling reactions of aryl bromide derivatives 3a with phenylboronic acid 8a in water or water/DMF under ambient conditions was achieved (Scheme 52). Maximum conversions were obtained in the presence of tetrabutylammonium bromide (TBAB) as a phase-‐transfer catalyst and K2CO3 as a base as shown in Table 22. In comparison, palladium precatalyst 100 showed a higher con-version due to its poor solubility in water. On the other hand, palla-dium precatalyst 99 was efficient to afford the targeted biaryls 5 with excellent conversion and yields (Table 22). In general, several aryl bromides 3a could be coupled in excellent yields of targeted biaryls 5 as shown in Table 22 [63].

Conditions:Cat. conc.1.5 mmol%Solvent: DMF/H2OBase: Cs2CO3Co-catalyst: noneTemperature: 80 oC/!Time:2 h

+ BOH

OH

3a,c 8a

X

RR

N

N

N

PdClCl

5

91

Scheme 50. Suzuki-‐Miyaura cross-‐coupling reaction of aryl halides 3a,c and phenylboronic acid 8a using complex 91 as precatalyst.

Table 21. Suzuki-‐Miyaura cross-‐coupling reaction of aryl halides 3a,c and phenylboronic acid 8a using complex 91 as pre-catalyst.

Entry X R Yield %

1 Br 4-Ac 100

2 Br 4-NH2 95.1

3 Br 4-NO2 97.7

4 Br 4-MeO 98.9

5 Br 2-MeO 99.3

6 Br 4-F 62.3

7 Cl 4-Ac 74.5

8 Cl 4-MeO 38

9 Cl 4-CN 85.4

10 Cl 4-COOMe 78.4

11 Cl H 34

N

S

OHOPdCl2(MeCN)2

MeCN

N

S

OHO

PdCl

Cl

S

NO

Pd

S

NOor

98 99 100



In addition, the catalytic activity of the pyridine-based palla-dium complexes 99 and 100 was examined for the double cross-coupling between aryl bromide derivatives 3a and 1,4-‐phenylenedi-boronic acid 101 as shown in Scheme 53. The precatalysts 99 and 100 showed an excellent efficiency to afford the corresponding teraryls 102 in excellent yield at lower catalyst loading of 0.1-0.5 mol% (Scheme 53, Table 23), [63].

The reaction chloroalkyl-functionalized mesoporous silica nanospheres 103 with 2-aminopyridine 58 followed by complexa-tion with palladium acetate produces the catalyst pyridine-based palladium complex 105 on mesoporous silica nanospheres (Scheme 54) [64].

This newly developed catalytic system 105 showed excellent ability in the catalysis of Suzuki-Miyaura cross-coupling reactions

Conditions:Cat. conc.:0.01-1 mol%Solvent: H2O or DMF/H2OBase: K2CO3Co-catalyst: TBABTemperature: 90-110 oCTime:5-24 h

+ BOH

OH

3a 8a

Br

RR

99 or 100

NS

OHO

PdClCl

S

NO

Pd

S

NOor

5

Scheme 52. Suzuki–Miyaura cross-coupling of phenylboronic acid 8a and aryl bromide 3a catalyzed with 99 and 100.

Table 22. Suzuki–Miyaura cross-coupling of phenylboronic acid 8a and aryl bromide 3a catalyzed with 99 and 100.

Yield % Entry R

Cat 99 Cat 100

1 4-NO2 98 99

2 4-CN 95 95

3 4-CHO 95 98

4 4-COOH 94 96

5 4-Me 95 95

6 4-MeO 96 95

7 4-Ac 92 90

8 H 95 99

Conditions:Cat. conc.:0.1-0.5 mol%Solvent: H2O or DMF/H2OBase: K2CO3Co-catalyst: TBABTemperature: 90-110 oCTime:6-24 h

+ BOH

OH

3a 101

Br

99 or 100

NS

OHO

PdClCl

S

NO

Pd

S

NOor

BHO

HO

RRR

102

Scheme 53. Suzuki–Miyaura cross�coupling of 1,4-‐phenylenediboronic acid 101 and aryl bromide 3a catalyzed with 99 and 100.


between aryl halides 3a-c and phenylboronic acid 8a in water (Scheme 55). The biaryls 5 was obtained by using pyridine-based palladium complex 105 on mesoporous silica nanospheres in excel-lent yields (Table 24). Catalyst recovery could be done by simple filtration and without the loss of its catalytic activity for 8 consecu-tive catalytic runs [64].

Treatment of the Schiff base 106 of 1,2-phenylenediamine and pyridine-2-carboxaldehyde with palladium acetate in acetonitrile afforded two types of palladium complexes 107 and 108, depending on the molar ratio of the palladium acetate and the ligand as shown in Scheme (56) [65].

The synthesized phosphine-free pyridine-based palladium com-plexes showed high efficiency to catalyze the Suzuki– Miyaura cross-coupling reactions of aryl halides 3a-c and aryl boronic acids 8 in water or water/glycerol as a green media at room temperature (Scheme 57). In general, the biaryls 5 obtained from cross-coupling of aryl bromide 3a and iodides 3b are of excellent yields in water without using of any co-catalyst. However, aryl chlorides 3c showed a variable behavior in coupling with aryl boronic acids 8 in aqueous-glycerol at higher reaction temperature (80 oC) (Table 25) [65].

Table 23. Suzuki–Miyaura cross-coupling of 1,4-‐phenylenediboronic acid 101 catalyzed with 99 and 100.

Yield % Entry R

Cat 99 TON Cat 100 TON

1 4-NO2 98 1960 99 9800

2 4-CN 95 1900 95 9500

3 4-CHO 95 1900 98 9800

4 4-COOH 94 940 96 1920

5 4-Me 95 950 95 950

6 4-MeO 96 960 95 950


Conditions:Cat. conc.:0.03 gSolvent: H2OBase: K2CO3Co-catalyst: noneTemperature:80 oCTime:4-10 h

+ BOH

OH

3a-c 8a

X

RR

Pd

NNH

AcO OAc

105

5

Scheme 55. Suzuki–Miyaura cross-coupling of alkylhalides 3a-c with phenylboronic acid 8a catalyzed with 105.


Table 24. Suzuki–Miyaura cross-coupling of alkylhalides 3a-c with phenylboronic acid 8a catalyzed with 105.

Entry X R Yield %

1 Br H 99

2 I H 99

3 I 4-MeO 98

4 I 4-NO2 98

5 Br H 99

6 Br 4-MeO 96

7 Br 4-Me 90

8 Br 4-Ac 98

9 Br 4-NO2 96

10 Br 2-NO2 94

11 Br 2-Pyridyl 93

12 Br 2-Thienyl 88

13 Cl H 80

14 Cl 4-Ac 82

NN

NN

Pd(OAc)2

MeCN/! 6 h

Pd(OAc)2

MeCN/! 6 h

1 ligand :1 Pd(OAc)2

1 ligand :2 Pd(OAc)2

NN

NN

NNNN

Pd

OAcAcO

PdOAcOAc

Pd

OAcAcO

106

107

108 Scheme 56. Synthesis of complexes 107 and 108.

NNNN

PdOAcOAc

Pd

OAcAcO

Conditions:Cat. conc.:0.2 or 1 mol%Solvent: H2O or H2O/GlycerolBase: K2CO3Co-catalyst: noneTemperature: rt. or 80 oCTime: 2-24 h

+ BOH

OH

3a-c 8

X

R1R1R2 R2

5

108

Scheme 57. Suzuki–Miyaura cross-coupling reactions of aryl halides 3a-c and aryl boronic acids 8 in water or water/glycerol as a green media.


Table 25. Suzuki–Miyaura cross-coupling reactions of aryl halides 3a-c and aryl boronic acids 8 in water or water/glycerol as a green media.


1 Br 4-NO2 H 98

2 Br 4-NO2 4-Cl 96

3 Br 4-NO2 4-Me 94

4 Br 4-Ac H 98

5 Br 4-CHO H 92

6 Br H H 96

7 Br H 4-Me 98

8 Br 4-Me H 99

9 Br 4-MeO H 99

10 Br 4-MeO 4-Cl 92

11 Br 4-MeO 4-Me 98

12 Br 2-Me H 86

13 Br 2-MeO H 92

14 Br 1,3-Me2 H 82

15 I H H 98

16 I 4-MeO H 98

17 Cl 4-NO2 H 82

18 Cl 4-NO2 4-Cl 56

19 Cl 4-NO2 4-Me 68

20 Cl 4-Ac H 76

21 Cl H H 86

22 Cl 4-Me H 74

23 Cl 4-MeO Me 62

24 Cl 2-MeO H trace

25 Cl 2-Me H 12

N

COOMe

BrBr

CuI,

Cs2CO3/ DMF, 140 oC

N

HN

N

COOH

N

N

N

N

N

COOH

N

N

N

N

n-BuBr

90 oC

BuBu BrBr

Pd(AcO)2/ DMSO

!w/ 165 oC

N

COOH

N

N

N

N

BuBu

Pd

Br

Br

109

110

111

112 113 Scheme 58. Synthesis of pyridine-pendent to bis-benzimidazole palladium complex 113.

A new pyridine-pendant to bis-benzimidazole palladium com-plex 113 have been prepared via a series of reactions as shown in Scheme 58. The key intermediate compound bis-benzimidazolyl

isonicotinic acid 111 was synthesized via the reaction between ben-zimidazoles 110 and 109 in the presence of CuI in dry dimethyl-formamide, followed by installing alkyl groups to give the pyridine-


Conditions:Cat. conc.: 0.005 mol%Solvent: H2O or H2O/MeOH or NMPBase: K2CO3Co-catalyst: noneTemperature: 100 oCTime: 3-24 h

+ BOH

OH3a,b

8

X

R1

R1

R2

R2

5N

COOH

NN

NN

BuBuPdBr

Br

or

Het-X

or

HetR2

113

13 or 114

13, Het = 2-Pyridyl114, Het = 3-quinolinyl

14 or 115

14, Het = 2-Pyridyl115, Het = 3-quinolinyl

Scheme 59. Suzuki–Miyaura cross-couplings of aryl or heteroaryl halides 3a,b, 13 or 114 with aryl boronic acids 8 using complex 113 as precatalyst.

Table 26. Suzuki–Miyaura cross-couplings of aryl or heteroaryl halides 3a,b, 13 or 114 with aryl boronic acids 8 using complex 113 as precatalyst.


1 Br 4-Ac H 99

2 Br 4-Ac 2-Me 99

3 Br 4-Ac 3-Me 99

4 Br 4-Ac 4-Me 99

5 Br 4-Ac 2-MeO 94

6 Br 4-Ac 3-MeO 95

7 Br 4-Ac 4-MeO 93

8 Br 4-Ac 4-Ac 99

9 Br 4-Ac 4-F 99

10 Br 4-Ac 4-CF3 99

11 Br 4-Ac 2-naphthyl 98

12 Br H H 99

13 Br 2-Me H 98

14 Br 3-Me H 98

15 Br 4-Me H 97

16 Br 4-MeO H 99

17 Br 4-Cl H 99

18 Br 4-CN H 99

19 Br 4-EtO H 93

20 Br 4-F H 99

21 Br 4-NO2 H 99

22 Br 3,4-(CF3)2 H 95

23 Br 1-Naphthyl H 95

24 Br 2-Pyridyl H 83

25 Br 3-Quinolinyl H 87

26 I H H 90

27 I 4-Me H 72

28 I 4-MeO H 97

29 I 4-CF3 H 83

30 I 1-Naphthyl H 90


N

N NR R

116, R = 4-MeOC6H4-

117, R = 2,6-Me2C6H3-

PdCl2(MeCN)2/ NH4PF6

DCM

N

N NR R

118, R = 4-MeOC6H4-

119, R = 2,6-Me2C6H3-

Pd

Cl

PF6


Conditions:Cat. conc.: 0.5-1 mol%Solvent: H2O Base: K3PO4Co-catalyst: noneTemperature: 80 oCTime: 1-5 h

+ BOH

OH

3a,c 8

X

R1R1R2 R2

5

NN N

R R

119, R = 2,6-Me2C6H3-

Pd

Cl

PF6

Scheme 61. Suzuki–Miyaura cross-coupling reaction of aryl bromides and chlorides 3a,c with arylboronic acids 8 using complex 119 as precatalyst.

bridged bis-benzimdazolium dibromide 112 (Scheme 58). Treat-ment of the salt 112 with palladium acetate in dimethylsulfoxide under microwaves irradiation afforded the corresponding pincer-type palladacycle 113 [66, 67].

The catalytic activity of novel pyridine-based palladacycle 113 was performed in the Suzuki–Miyaura cross-coupling of aryl bro-mides 3a, iodides 3b and heteroaryl bromides 13 or 114 with aryl boronic acids 8 in different types of solvents including water and in the presence of potassium carbonate as a base (Scheme 59) [66, 67].

Regardless the nature and the position of substituents in boronic acids 8, excellent yields were obtained for the biaryls 5 or het-eroaryl aryls 115 (Table 26).

The reaction of the mixture of PdCl2(CH3CN)2 and NH4 PF6 with bis(imino)pyridine ligands 116 or 117 in dichloromethane at room temperature afforded the corresponding bis(imino)pyridine palladium(II) complexes 118 and 119 (Scheme 60) [68].

The catalytic applicability of complex 119 in the Suzuki–Miyaura cross-coupling reaction of aryl bromides 3a and chlorides 3c with arylboronic acids 8 was examined in the presence of K3PO4·3H2O as a base at 80 °C as shown in Scheme (61). Excellent yields of 5 were obtained after only 3 h of coupling reaction, and all aryl bromides 3a that even have an ortho-‐substituted group, reacted effectively to give the desired coupling products in good to excel-lent yields. Also, the cross-coupling of aryl chlorides 3c, which showed to have an electron-‐accepting group, afforded the corre-

sponding biaryls 5 in good yields. In contrast, aryl chlorides 3c have an electron-‐releasing group at meta-position (methoxy group) which afforded the corresponding biaryls 5 in only 25% yield (Ta-ble 27, entry 21), whereas 4-chloroanisole failed to give any cou-pling products under the same reaction conditions (Table 27, entry 19) [68].

The same catalytic system was also used to prepare fluorinated biphenyl liquid crystals 120 in excellent yields (93–95%) by the reaction of 4-‐fluorophenylboronic acid 8, with aryl bromide 3a using different concentrations of surfactants (Scheme 62) [68].

Novel pyridine-based palladium complexes 122 have been de-veloped by Dong-Hwan et al. and proved to be thermally stable and under oxygen or water. Thus, the reactions of pyridylazetidine ligand 121 with palladium chloride, followed by precipitation as perchlorate in methanolic solution afforded the new palladium(II) complex 122, containing functionalized pyridylazetidine as de-picted in Scheme (63) [69].

The newly synthesized complex 122 showed high efficiency as precatalysts for Suzuki cross-coupling reactions in water. Different aryl halides 3a,c undergo coupling with phenylboronic acid 8a in water, potassium carbonate as a base and in the presence of TBAB as a co-catalyst (Scheme 64). Regardless of the identity of the hal-ide used, the catalyst system was successful to obtain the biaryls 5 in good to excellent yields in water (Table 28) [69].


Table 27. Suzuki–Miyaura cross-coupling reaction of aryl bromides and chlorides 3a,c with arylboronic acids 8 using complex 119 as precatalyst.


1 Br 4-MeO H 90

2 Br 4-Ac H 96

3 Br 4-Me H 85

4 Br 2-Me H 80

5 Br 4-F H 90

6 Br 4-COOh H 99

7 Br 4-OH H 98

8 Br 4-MeO 4-F 91

9 Br 4-Ac 4-F 96

10 Br 4-COOH 4-F 97

11 Br 4-OH 4-F 98

12 Br 4-MeO 4-Me 94

13 Br 4-Ac 4-Me 98

14 Br 4-NO2 H 96

15 Cl 4-CN H 93

16 Cl 4-Ac H 88

17 Cl 4-MeO H 0

18 Cl 4-Ac 4-Me 85

19 Cl 3-MeO 4-Me 25

Conditions:Cat. conc.: 0.5 mol%Solvent: H2O Base: K3PO4Co-catalyst: surfactantsTemperature: 80 oCTime: 3 h

+

BHO OH

3a8

Br

120

NN N

R R

119, R = 2,6-Me2C6H3-

Pd

Cl

PF6

FR

C6H11

Yield = 93-95%

R = C6H11

F

Scheme 62. Suzuki–Miyaura cross-coupling reaction of aryl bromides 3a with 4-‐fluorophenylboronic acid 8 using complex 119 as precatalyst.


NN

HNPdCl2/MeOH N

N

NPd

ClO4

ClO4

Cl

121 122

Scheme 63. Synthesis of Pd(II) complex 122.

Conditions:Cat. conc.: 0.01-1 mol%Solvent: H2O Base:Na2CO3Co-catalyst: TBABTemperature: 50-90 oCTime: 2-24 h

+ BOH

OH

3a,c 8a

X

RR

5

N

N

NPd ClO4

Cl

122

Scheme 64. Suzuki–Miyaura cross-coupling reaction of aryl bromides and chlorides 3a,c with phenylboronic acids 8a using complex 122 as precatalyst.

New ligands containing the 2,2′-‐dipyridylamine moiety of con-siderable water solubility have been synthesized as shown in Scheme 65 via alkylation of 2,2′-‐dipyridylamine 123 with dibromo compounds 124 and 128 and subsequent quaternization to afford the corresponding ionic nitrogen-‐containing pyridine-based chelat-ing ligands 126 and 130. Next, the complexation of the latter ligands with that of palladium acetate afforded the palladium com-plexes 127 and 131 (Scheme 65) [70].

The newly prepared ionic pyridine-based palladium complexes 127 and 131 have been used as catalysts for the Suzuki–Miyaura cross-‐coupling reaction in water and they showed high catalytic activities in the cross-‐coupling of aryl halides 3a,c in the presence of base and co-catalysts in clean water (Scheme 66, Table 29) [70].

2-Acetylpyridine 132 reacted with 4-methoxycarbonyl-benzaldehyde 133 in ammonia to give the intermediate terpyridine

Table 28. Suzuki–Miyaura cross-coupling reaction of aryl bromides and chlorides 3a,c with phenylboronic acids 8a using complex 122 as precata-lyst.

Entry X R Yield %

1 Br 4-NO2 99

2 Br 2-MeO 94

3 Br 4-MeO 93

4 Br 2-Me 92

5 Br 4-Me 93

6 Br 4-OH 91

7 Cl H 92

8 Cl 4-NO2 96

9 Cl 2-MeO 80

10 Cl 4-MeO 93

11 Cl 2-Me 90

12 Cl 4-Me 91


N N

HN

NaF/ DMF

NaF/ DMF

Br-(CH2)6-Br

OOBr

Br

N N

N

Br

N N

N

O

O

Br

R3N

R3N

N N

N

NR3

N N

N

O

O

NR3

Br

Br

Pd(OAc)2

Pd(OAc)2

N N

N

O

O

NR3

Br

PdAcO OAc

N N

N

NR3 Br

PdAcO OAc

R =Me, nBu

R = Me

123

124

125126

127

128

129

130

131 Scheme 65. Synthesis of complexes 127 and 131.


Conditions:Cat. conc.:0.1 mmolSolvent: H2OBase: K2CO3, KOH, or Bu4NOHCo-catalyst: TBAB, SDS, or SDBSTemperature: 100-120 oCTime: 0.5-3 h

+ BOH

OH

3a,c

X

R1R1R2 R2

N N

NXNR3 Br

PdAcO OAc

8

5

127 or 131

Scheme 66. Suzuki–Miyaura cross-‐coupling reaction between aryl halides 3a,c and arylboronic acid 8 in the presence of complexes 127 or 131.

Table 29. Suzuki–Miyaura cross-‐coupling reaction between aryl halides 3a,c and arylboronic acid 8 in the presence of complexes 127 or 131.


1 Br 4-Ac H 89

2 Br 4-CHO H 98

3 Br 4-MeO H 99

4 Br 4-OH H 99

5 Br 3-OH H 96

6 Br 4-COOH H 94

7 Br 3-COOH H 98

8 Br 4-CN H 98

9 Br 4-NO2 H 99

10 Br 4-Meo H 80

11 Br 4-Me H 52

12 Br 3-Me H 70

13 Br 2-Me H 25

14 Br 4-Ac 4-CHO 95

15 Br 4-COOH 4-F 98

16 Br 4-Ac 3-F 97

17 Br 4-Ac 4-MeO 98

18 Br 4-Ac 4-Me 100

19 Br 4-Ac 3-Me 100

20 Br 4-Ac 2-Me 99

21 Cl 4-Ac H 76

22 Cl 4-Ac 4-CHO 100

23 Cl 4-Ac 4-F 78

24 Cl 4-Ac 3-F 89

25 Cl 4-Ac 4-Me 85

26 Cl 4-Ac 4-MeO 80

27 Cl 4-NO2 H 98

28 Cl 4-NO2 4-Me 85

29 Cl 4-NO2 4-F 100

30 Cl 4-NO2 3-F 100

31 Cl 2-NO2 H 61

32 Cl 4-MeO H 45

33 Cl 4-Ac H 100

34 Cl 4-Ac 4-MeO 92


CHO

COOMe

N COMe

NH3/ NaOH

EtOH

N

NN

COOH

Tena Gel

EDCl, HOBt/ DMSO

PdCl2(MeCN)2

N

NN

NHO

C O

nPS

PdCl Cl

H3N

O

O

n

PS

132

133

134

135

136


Conditions:Solvent: H2OBase: K2CO3Co-catalyst: noneTemperature: 100 oCTime: 6-12 h

+ BOH

OH

3a,b 8

X

R1R1R2 R2

5

N

NN

HNO C

O

nPS

PdCl Cl

136

Scheme 68. Suzuki–Miyaura cross-coupling reaction of aryl bromides and iodide 3a,b with arylboronic acids 8 using complex 136 as precatalyst. acid 134 which has been immobilized on amphiphilic PS-PEG resin 135 in dimethyl sulfoxide to afford the resin-bound terpyridine ligand (Scheme 67). The complexation of the generated resin-bound terpyridine ligand 134 with palladium source afforded the PS-PEG resin-supported terpyridine-based palladium complex 136 as shown in Scheme (67) [71].

The PS-PEG resin-supported terpyridine-based palladium com-plex 136 effectively catalyzed the aerobic Suzuki–Miyaura cross-coupling reaction of aryl bromides 3a and iodides 3b with substi-tuted arylboronic acids 8 under aqueous conditions (Scheme 68). Biaryls 5 were obtained in high yields regardless of the nature of the substituent in the aryl halide (Table 30). It should be noted that polymeric catalyst 136 could be easily recovered and reused for a number of catalytic cycles with no significant loss of its catalytic performance [71].

3.1.2. Pyran-based Palladium Complexes 1,2-Diaminocyclohexane 139 was reacted with 6-‐O-‐mono-

tosyl-‐β-‐CD 138 in dimethylformamide to afford water soluble 6-‐O-‐monotosyl-‐β-‐CD grafted with the diamine 140 as depicted in Scheme (69). Then, the latter ligand 140 was treated with palladium acetate in toluene and stirred at room temperature for 24 h to give the water-soluble diaminocyclohexane palladium-‐β-‐CD complex 141 as a pure yellow powder [72].

The catalytic activity of the water-soluble diaminocyclohexane palladium-‐β-‐CD complex 141 as a catalyst for the Suzuki–Miyaura cross-coupling reaction in water was examined with the reaction of aryl halides 3a,b and various arylboronic acids 8, using the opti-mized reaction conditions (Scheme 70). Generally, the catalyst 141 showed a good catalytic performance giving the targeted biaryls 5 in good to excellent yields (Table 31). It was found that even after


ten catalytic cycles, the activity of diaminocyclohexane palla-dium-‐β-‐CD complex 141 was not lost [72].

Schiff base-Chitosan 142 was mixed with methanol solution of sodium tetrachloropalladate to afford the new chitosan-based palla-dium (II) complex 143 (Scheme 71) [73].

The catalytic activity of the new chitosan-based palladium (II) complex 143 in solvent free synthesis of biaryls 5 via Suzuki–Miyaura cross-coupling reactions under microwave irradiation was investigated as depicted in Scheme 72. The new chitosan-based palladium (II) precatalyst 143 exhibited high conversions and ex-

Table 30. Suzuki–Miyaura cross-coupling reaction of aryl bromides and iodide 3a,b with arylboronic acids 8 using complex 136 as precatalyst.


1 I H H 89

2 I 4-Me H 98

3 I 4-MeO H 99

4 I 4-CF3 H 99

5 I 2-Me H 96

6 I 3-Me H 94

7 I 1-naphthyl H 98

8 Br H H 98

9 Br 4-Me H 99

10 Br 4-MeO H 80

11 Br 4-CF3 H 52

12 I H 4-Me 70

13 I H 2-Me 25

14 I H 3-Me 95

15 I H 1-naphthyl 98

16 I H 4-CF3 97

17 I H 4-Cl 92

O

O O

OH

OHHO

O

O O

OTs

OHHO

O

O O

NH

OHHO

NH2

O

O O

NH

OHHO

NH2

Pd OAc

OAc

TosCl, NaOH

CH3CN, H2O

DMF, 80°C

NH2

NH2

Pd(OAc)2toluene

137 138

139

140

141 Scheme 69. Synthesis of diaminocyclohexane palladium-‐β-‐CD 141.


cellent yields in case of coupling of aryl bromides 3a with phenyl boronic acid 8a. On the other hand, aryl iodides 3b gave good yields, whereas aryl chlorides 3c afforded the products 5 in low yields (Table 32). Chitosan-based palladium (II) catalyst 143 could be used effectively for several catalytic runs in Suzuki cross-coupling reactions [73].

3.2. Six Membered with Two Heteroatom Heterocycles-Based Palladium Complexes

3.2.1. Piperazine -based Palladium Complexes Refluxing a mixture of functionalized polystyrene 145 and N-

phenylpiperazine 144 in acetonitrile gave the polystyrene-supported N-phenylpiperazine ligand 146 (Scheme 73). Heating the latter

Conditions:Cat. conc.:0.001 mol%Solvent: H2OBase: Cs2CO3Co-catalyst: noneTemperature:80 oC/ !Time:1-24 h

+ BOH

OH

3a,b 8

X

R1R1R2 R2

5

O

O O

NH

OHHO

NH2

Pd OAcOAc

141

Scheme 70. Suzuki–Miyaura cross-coupling reactions between aryl halides 3a,b and arylboronic acid 8 using diaminocyclohexane palladium-‐β-‐CD complex 141.

Table 31. Suzuki–Miyaura cross-coupling reactions between aryl halides 3a,b and arylboronic acid 8 using diaminocyclohexane palladium-‐β-‐CD complex 141.


1 I H H 99

2 Br H H 98

3 Br 4-Ac H 93

4 Br 4-MeO H 96

5 Br 4-CHO H 95

6 Br 2-CHO H 65

7 Br 4-Ac 4-Me 96

8 Br 4-MeO 4-Me 98

9 Br 4-CHO 4-Me 95

10 Br 4-Ac 3-Me 94

11 Br 4-MeO 3-Me 96

12 I 4-MeO 3-Me 97

13 Br 4-CHO 3-M 95

14 I 2-MeO 4-F 76

15 Br 4-Ac 4-F 96

16 Br 4-MeO 4-F 97

17 Br 3-NO2 4-F 90

18 Br 4-CHO 4-F 96

19 I 4-Me 4-F 94

20 I 4-Me 4-Ac 95


polymeric ligand 146 with PdX2(MeCN)2 in ethanol for 12 h af-forded the functionalized polymer palladium complex 147 [74].

This synthesized heterogeneous PS-palladium(II) complex 147 showed high catalytic efficiency for the Suzuki-Miyaura cross-coupling of halo pyridines 13 and various arylboronic acids 8 to give the corresponding 2-arylpyridines 14 (Scheme 74, Table 33).

The coupled products 14 were obtained in excellent yields at low catalyst loadings under mild reaction conditions. The cross-coupling has been extended for other heterocyclic bromides 148 to give the desired coupling products 149 in good yields (Scheme 75, Table 34). Further, this heterogeneous catalyst 147 showed excel-lent recyclability and reused for 4 cycles with no significant de-crease in its activity [74].

OOHO

N

O

OCH2COOH

N

HOOC

Na2PdCl4

Water

OOHO

N

O

OCH2COOH

N

HOOC

PdCl

Cl

nn

142 143

Scheme 71. Synthesis of chitosan based palladium (II) complex 143.

Conditions:Cat. conc.:0.015 mol%Solvent: solvent freeBase: K2CO3Co-catalyst: noneTemperature: 50 oC/µwTime:4 min

+ BOH

OH

3a-c 8a

X

RR

OOHO

NO

OCH2COOH

N

HOOC

PdCl

Cl

n

143

5

Scheme 72. Suzuki–Miyaura cross-coupling reaction of aryl halides 3a-c with phenylboronic acids 8a using complex 143 as precatalyst. Table 32. Suzuki–Miyaura cross-coupling reaction of aryl halides 3a-c with phenylboronic acids 8a using complex 143 as precatalyst.

Entry X R Yield % TON TOF (h-1)

1 Br 3-MeO 92 6133 102217

2 Br 4-MeO 97 6467 107783

3 Br 3-NO2 90 6000 100000

4 I 4-MeO 87 5800 96667

5 I 3-NO2 81 5400 90000

6 Cl 4-MeO 53 3533 58883

7 Cl 3-NO2 23 1533 25550


144

N

N

Ph

H

+

Cl

NaI/MeCN

70 oC N

N

Ph

PdX2(MeCN)2

EtOH/ !/ 12"

N NPh

PdX X

X = Cl, Br145 146147


N NPh

PdCl Cl

+ BOH

OHConditions:Cat. conc.:0.5 mol%Solvent: H2O/EtOHBase: K3PO4Co-catalyst:NoneTemperature:100 oC/ reflux (!)Time: 8 h

13 8

N

14

Ar

X = Br or Cl

147

X

RN Ar

R

Scheme 74. Suzuki-Miyaura cross-coupling of halo pyridines 13 and various arylboronic acids 8 using complex 147 as precatalyst.

Table 33. Suzuki-Miyaura cross-coupling of halo pyridines 13 and various arylboronic acids 8 using complex 147 as precatalyst.


1 Br H C6H5- 91

2 Br H 4-MeC6H4- 85

3 Br H 3-MeC6H4- 86

4 Br H 4-OEtC6H4- 82

5 Br H 3-OEtC6H4- 84

6 Br H 4-tBuC6H4- 79

7 Br H 4-VinylC6H4- 75

8 Br H 4-CF3C6H4 79

9 Br H 4-MeCOC6H4- 82

10 Br H 4-CNC6H4- 72

11 Br H 1-Naphthyl 88

12 Br H 3,4-CH2O2C6H3- 85

13 Br H 4-FC6H4- 78

14 Br 5-Me 4-MeOC6H4- 78

15 Br 5-Me C6H5- 74

Table 33. contd…



16 Br 6-Me C6H5- 65

17 Br 6-MeO C6H5- 69

18 Br 3-Me 4-FC6H4- 71

19 Br 4-Me 3,4-CH2O2C6H3- 81

20 Br 5-Me 1-Naphthyl 80

21 Cl H C6H5- 58

22 Cl H 3-MeC6H4- 62

23 Cl H 4-CF3C6H4- 54

24 Cl H 4-MeCOC6H4- 58

25 Cl H 4-CNC6H4- 50

26 Cl H 4-FC6H4- 49

N NPh

PdCl Cl

+ BOH

OH Conditions:Cat. conc.:0.5 mol%Solvent: H2O/EtOHBase: K3PO4Co-catalyst:NoneTemperature:100 oC/ reflux (!)Time: 8 h

148 8a 149

147

Het

Het

Br

Scheme 75. Suzuki-Miyaura cross-coupling of heterocyclic bromides 148 and various phenylboronic acid 8 using complex 147 as precatalyst. Table 34. Suzuki-Miyaura cross-coupling of heterocyclic bromides

148 and various phenylboronic acid 8 using complex 147 as precatalyst.

Entry Het Yield %

1 N

N

79

2 S

72

3 N

81

7 N

79

3.3. Six Membered with Three Heteroatom Heterocycles-Based Palladium Complexes

3.3.1. Triazine-based Palladium Complexes A new catalyst 151 containing triazine-based nano-silica poly-

mer incorporated Pd nanoparticle has been described by Isfahani et al. through immobilization of palladium on the dendritic polymer 150 which hasbeen achieved by mixing the polymer with palladium chloride/sodium chloride mixture for 24 h at 60 oC, followed by treatment with sodium acetate as shown in Scheme (76) [75].

This new catalyst 151 exhibited high catalytic activity in the Suzuki-Miyaura cross-coupling of aryl halides 3a,c with arylbo-ronic acids 8 thermally and under microwaves irradiation (Scheme 77). The optimized reaction conditions using dimethylformamide (DMF)/water mixture in the presence of K2CO3 as a base and 0.006 mol % of catalyst loading, gave the targeted products 5 in high to excellent yields, under thermal as well as microwave conditions (Table 35) [75].

Moreover, the triazine-based polymeric catalyst 151 was easily recovered from the reaction mixture and reused with no significant


loss of its activity. ICP analysis pointed out that palladium leaching from the catalyst was only in trace amounts in the first 2 runs [75].

Treatment of 4,4′,4“-‐(1,3,5-‐triazine-‐2,4,6-‐triyl)tribenzaldehyde 152 with 1,4-‐diaminobenzene 153 in dioxane/ acetic acid mixture afforded the corresponding ligand 154 as shown in Scheme 77. The latter reacted with palladium acetate in dichloromethane at room temperature for 8 h gave the new heterogeneous complex 155 which is low cost and a thermally stable catalyst (Scheme 78) [76].

The catalytic activity of the reusable heterogeneous triazine-based palladium complex 155 in Suzuki-‐Miyaura cross-coupling reaction at room temperature has been examined (Scheme 79). Thus, a variety of aryl halides 3a-c and arylboronic acids 8 in an aqueous medium were allowed to react in the presence of K2CO3 base, at room temperature for 2 hrs, to give excellent yields (in case of bromides 3a and iodides 3b) of the biaryls 5 as shown in Table 36 [76].

4. BENZO-FUSED FIVE-MEMBERED HETEROCYCLES-BASED PALLADIUM COMPLEXES

4.1. Indole-Based Palladium Complexes A reusable heterogenous iron oxide immobilized isatin-based

palladium complex 159 has been developed by Sara et al. The sup-

ported Pd catalyst 159 was obtained by the reaction of palladium (ΙΙ) acetate with the synthesized isatin-Schiff base-‐γ-‐Fe2O3 158 in methanol as shown in Scheme (80) [77].

The synthesized recyclable magnetic catalyst 159 was used in Suzuki-‐Miyaura cross-coupling reactions of various arylhalides 3a-c and phenylboronic acid 8a under solvent-free conditions (Scheme 81). The catalyst 159 exhibited excellent activity with aryl iodides 3b regardless of the nature of the substituent, whereas good to ex-cellent yields were obtained in case of aryl bromides 3a and chlo-rides 3c (Table 37) [77].

4.2. Benzothiazole-Based Palladium Complexes

Recently, we have reported the synthesis of benzthiazolyl based Palladium (II)-complex 163 by the reaction of benzyl derivative of 2-benzothiazolyl-oxime 162 with equimolar amount of sodium tetrachloropalladate in methanol at room temperature (Scheme 82). The catalytic activity of the synthesized precatalyst 163 in the Su-zuki-Miyaura cross-coupling reaction was applied and examined in the synthesis of novel candidates, 3-(5-arylbenzofuran-2-yl)-1H-pyrazole derivatives 165 (Scheme 83). Thus, Suzuki-Miyaura cross-coupling reaction of the deactivated 3-(5-bromobenzofuran-2-yl)-1H-pyrazole 164, with arylboronic acids 8 in the presence of the benzothiazole-oxime-based Palladium(II) complex 163 was found

N

N

N

N

NHN NH2

NH2

NH2NH2

N

N

N

N

N NHH2N

H2N

NH2 NH2

N

N

N

N

NNH

SiO

O 2n Silica

N

N N

N

N

HN

NH2NH2

NH2

NH2

NN

NN

NNH

H2N

H2N

NH2

NH2

N

N

N

N

NHN NH2

NH2

NH2NH2

N

N

N

N

N NHH2N

H2N

NH2 NH2

N

N

N

N

NNH

SiO

O 2n Silica

N

N N

N

N

HN

NH2NH2

NH2

NH2

NN

NN

NNH

H2N

H2N

NH2

NH2

PdCl2/ NaCl, MeOH, rt. 24 h

1-60 oC, 24 h2-AcONa, rt, 1h

PdPd

Pd

Pd Pd

Pd

Pd

Pd

Pd

Pd

Pd

Pd

Pd

Pd

Pd

Pdnp-nSTDP

150151


Pdnp-nSTDP

151

Conditions:Cat. conc.:0.006 mol% PdSolvent: H2O/DMFBase: K2CO3Co-catalyst: noneTemperature: 70-80 oC/ 200 w mw or rtTime: 2-24 h (!)/ 2-10 min (µw)

+ BOH

OH

3a,c

X

R1R1R2 R2

8

5

Scheme 77. Suzuki-Miyaura cross-coupling of aryl halides 3a,c and arylboronic acids 8 using complex 151 as precatalyst.


Table 35. Suzuki-Miyaura cross-coupling of aryl halides 3a,c and arylboronic acids 8 using complex 151 as precatalyst.

Entry X R1 R2 Δ Yield % µW Yield %

1 I H H 95 95

2 I H 4-MeO 96 92

3 I 4-Ac H 96 93

4 I 4-Me H 95 96

5 I 4-Ac 4-MeO 96 95

6 Br H H 95 94

7 Br H 4-MeO 94 95

8 Br 4-MeO H 96 93

9 Br 4-MeO 4-MeO 95 94

10 Br 4-Ac H 95 93

11 Br 4-Ac 4-MeO 95 95

12 Br 4-CHO H 90 92

13 Br 4-CHO 4-MeO 92 91

14 Br 4-CN H 94 92

15 Cl H H 84 94

16 Cl H 4-MeO 84 90

17 Cl 4-Ac H 83 92

18 Cl 4-Ac 4-MeO 81 93

19 Cl 4-CHO H 80 90

N

N

N

CHO

CHOOHC

NH2

NH2

AcOH/ dioxane!

NNN

N

N

NNN

NN N

NN

NNN

NN

N

N

NNN

NNN

N

NN

N

N

N

N

N

N

N

Pd(AcO)2

NNN

N

N

NNN

NN N

NN

NNN

NN

N

N

NNN

NNN

NN

NN

N

N

N

N

N

N

NNN

N

N

NNN

NN N

NN

NNN

NN

N

N

NNN

NNN

NN

NN

N

N

N

N

N

N

Pd

Pd

Pd

Pd

PdPd

Pd

Pd

Pd

OAcOAc

AcOAcO

AcOAcO

OAc

OAc

OAcOAc

AcOAcO

152

153

154

155

Scheme 78. Synthesis of Pd(II) complex 155.


Conditions:Cat. conc.:0.006 mol% PdSolvent: H2OCo-catalyst: noneTemperature: rt. Time: 2 h

+ BOH

OH

3a-c 8

X

R2R1R1 R2

5

155

Scheme 79. Suzuki-Miyaura cross-coupling of arylhalides 3a-c and arylboronic acids 8 using complex 155 as precatalyst.

Table 36. Suzuki-Miyaura cross-coupling of arylhalides 3a-c and arylboronic acids 8 using complex 155 as precatalyst.

Entry X R1 R2 Yield % TON

1 Br H H 98 1889

2 Br 3-NH2 H 91 1684

3 Br CHO H 83 1426

4 Br CN H 74 1293

5 Br MeO H 92 1564

6 Br 2-NO2 H 72 1132

7 Br CHO 4-CHO 80 1276

8 Br 4-Me 4-CHO 84 1340

9 Br 4-NO2 4-CHO 75 1033

10 Br H 4-CHO 85 1461

11 Br 2-NH2 H 70 1295

12 Br 4-CH2CN H 83 1346

13 I 4-NH2 H 90 1666

14 Br 4-Me 4-Me 95 1632

15 Br 4-CHO 4-Me 88 1404

16 Br 4-NH2 4-Me 93 1589

17 Br 4-MeO 4-Me 96 1516

18 I 4-NH2 4-Me 92 1572

19 Br H 4-MeO 85 1254

20 Br NO2 H 94 1598

21 Br H H 65 1320

22 Cl CHO H 30 515


!-Fe2O3

SiO

O

NH2

!-Fe2O3

SiO

O

N

NH

O

PdAcO OAc

NH

O

O

!-Fe2O3

SiO

O

NNH

O

Pd(AcO)2

156

157

158159


!-Fe2O3

SiO

O

N

NH

OPd

AcO OAc

Conditions:Cat. conc.:0.015 mol%Solvent: solvent freeBase: Et3NCo-catalyst: noneTemperature: 100 oCTime: 30-270 min

+ BOH

OH

3a-c 8a

X

RR

5

159

Scheme 81. Suzuki-Miyaura cross-coupling of arylhalides 3a-c and phenylboronic acid 8a using complex 159 as precatalyst. Table 37. Suzuki-Miyaura cross-coupling of arylhalides 3a-c and phenylboronic acid 8a using complex 159 as precatalyst.

Entry X R Yield %

1 I H 95

2 I 4-MeO 93

3 I 4-Cl 86

4 Br H 90

5 Br 4-MeO 70

6 Br 4-NO2 97

7 Br 4-CN 60

8 Cl H 90

9 Cl 4-NO2 93

10 Cl 4-CN 76


S

NN

CH3

O S

N

N

CH3O

S

N

N

CH3

Pd

Cl

Cl

160 162 163

OH

Br

Base

Na2PdCl4

MeOH

161

Scheme 82. Synthesis of benzthiazolyl based Palladium (II)-complex 163.

O

Br

N NH + Ar-BOH

OH

S

N

N

CH3

O

Pd

Cl

Cl

163

O

Ar

N NHConditions:Cat. conc.:0.25 mol%Solvent: H2O-DMFBase: KOH, TEA, or Cs2CO3Co-catalyst:TBABTemperature:160 oC/250 w µw or reflux (!)Time: 15-30 min (µw), 6-14 h (!)

164 1658

Scheme 83. Suzuki-Miyaura cross-coupling of 3-(5-bromobenzofuran-2-yl)-1H-pyrazole 164 with arylboronic acids 8 using complex 163 as precatalyst.

Table 38. Suzuki-Miyaura cross-coupling of 3-(5-bromobenzofuran-2-yl)-1H-pyrazole 164 with arylboronic acids 8 using complex 163 as precata-lyst.

Entry Ar Δ Yield % µW Yield %

1 C6H5- 90 88

2 4-MeC6H4- 80 84

3 4-MeOC6H4- 72 80

4 4-ClC6H4- 95 87

5 3,4-OCH2OC6H3- 70 73

6 3-Thienyl 42 53

to be efficient for Suzuki-Miyaura reactions in aqueous medium, under thermal heating and microwave-irradiation conditions to afford the corresponding coupling products 165 in good to excellent yields (Table 38) [34].

The same catalyst 163 has been used in Suzuki-Miyaura cross-coupling reactions of 2-acetyl-5-bromothiophene 166 with deacti-vated and activated aryl(heteroaryl)boronic acids 8 were carried out under two heating modes i.e., thermal heating and microwave irra-diation conditions as shown in Scheme (84) and Table 39. The cross-coupling reactions afforded 5-aryl(heteroaryl)-2-acetylthio-phene 167 under thermal, as well as microwaves irradiation condi-tions [35].

Furthermore, catalyst 163 has been used in Suzuki cross-coupling reactions of 4,2 disubstituted-1,3-thiazole 168 with deacti-vated and activated aryl(heteroaryl)boronic acids 8 were carried out

under two heating conditions; thermally and microwave irradiation conditions, as illustrated in Scheme 85 and Table 40 [35].

Although, both the coupling candidates 5-bromothiophene de-rivatives 166 and 168 have a bromine atom attached to the thio-phene moiety, the reactivity of the thiazole containing candidate 168 was clearly different from that of 166 under microwave irradia-tion condition in an aqueous medium. The optimization of the cata-lytic conditions led to scouting the appropriate coupling condition for such deactivated thiazolyl bromides [35].

The precatalysts 163 catalyzed the Suzuki cross-‐coupling of 3-‐[(5-‐bromothiophen-‐2-‐carbonyl]pyrrolo[2,1-‐a]isoquinoline deriva-tives 170 with aryl and heteroaryl boronic acids 8 under thermal heating and microwave irradiation as shown in Scheme (86) and Table 41 [36].


Conditions:Cat. conc.0.25 mol%Solvent: H2OBase: KOHCo-catalyst: TBABTemperature: 100 oC/!, 250W (µw)Time:1-10 h (!), 1-9 min (µw)

+ BOH

OH

8

Ar

S

N

N

CH3O

Pd

Cl

Cl

163

OS Br

OS Ar

166 167

Scheme 84. Suzuki-Miyaura cross-coupling of 2-acetyl-5-bromothiophene 166 with activated and deactivated aryl(heteroaryl)boronic acids 8 using complex 163 as precatalyst.

Table 39. Suzuki-Miyaura cross-coupling of 2-acetyl-5-bromothiophene 166 with activated and deactivated aryl(heteroaryl)boronic acids 8 using complex 163 as precatalyst.

Entry Ar Δ Yield % µW Yield %

1 C6H5- 93 95

2 4-ClC6H4- 97 92

3 4-MeOC6H4- 90 98

4 2-MeC6H4- 89 93

5 3-Thienyl 91 95

Conditions:Cat. conc.1 mol%Solvent: DMFBase: Cs2CO3Co-catalyst: noneTemperature: 160 oC/ 250W (µw)Time: 30-45 min (µw)

+ BOH

OH

8

Ar

S

N

N

CH3O

Pd

Cl

Cl

163S Br S ArS

N

S

N

168169

Scheme 85. Suzuki-Miyaura cross-coupling of 4-(5-bromothiophen-2-yl)-2-methyl-1,3-thiazole 168 with activated and deactivated aryl(heteroaryl)boronic acids 8 using complex 163 as precatalyst.

Table 40. Suzuki-Miyaura cross-coupling of 4-(5-bromothiophen-2-yl)-2-methyl-1,3-thiazole 168 with activated and deactivated

aryl(heteroaryl)boronic acids 8 using complex 163 as precatalyst.

Entry Ar µW Yield %

1 C6H5- 80

2 4-ClC6H4- 60

3 4-MeOC6H4- 76

4 2-MeC6H4- 63

5 3-Thienyl 0


Conditions:Cat. conc.0.25 mol%Solvent: DMFBase: KOHCo-catalyst: TBABTemperature: 160 oC/!, 250W (µw)Time:6-12 h (D), 10-15 min (µw)

+ BOH

OH

8

Ar

S

N

N

CH3

O

Pd

Cl

Cl

163

N

R

O

S

Br

N

R

O

S

Ar

170 171

Scheme 86. Suzuki-Miyaura cross-coupling of 3-‐[(5-‐bromothiophen-‐2-‐carbonyl]-pyrrolo[2,1-‐a]isoquinoline derivatives with aryl and heteroaryl boronic acids under thermal heating and microwave irradiation using complex 163 as precatalyst.

Table 41. Suzuki-Miyaura cross-coupling of 3-‐[(5-‐bromothiophen-‐2-‐carbonyl]pyrrolo[2,1-‐a]isoquinoline derivatives with aryl and heteroaryl bo-ronic acids under thermal heating and microwave irradiation using complex 163 as precatalyst.

Entry R Ar Δ Yield % µW Yield %

1 CN C6H5- 90 94

2 CN 4-ClC6H4- 93 94

3 CN 4-MeOC6H4- 90 95

4 CN 2-MeC6H4- 85 87

5 CN 3-Thienyl 90 91

6 CN 3,4-OCH2O-C6H3- 88 92

7 COOEt C6H5- 90 92

8 COOEt 4-ClC6H4- 88 95

9 COOEt 4-MeOC6H4- 91 94

10 COOEt 2-MeC6H4- 84 92

11 COOEt 3-Thienyl 89 96

12 COOEt 3,4-OCH2O-C6H3- 92 89

N

N

NHHO

MeO

PdCl2(PhCN)2

N

NH

NO

MeO

PdCl

NH

N

H2N

CHOHO

MeO

EtOH/AcOH

172

173

174 175 Scheme 87. Synthesis of complex 175. 4.3. Benzimidazole-Based

Recently, a new benzimidazole-based palladium(II) complex 175 was synthesized by the reaction of ligand 174 with PdCl2(PhCN)2 as shown in Scheme (87). The activity of the new complex 175 as a catalyst for Suzuki cross-coupling reactions was

evaluated in ionic liquid at ambient temperature. The reported new catalytic system was reused for cross-coupling reactions and recy-cled for 6 runs. Using optimized reaction conditions (Scheme 88) good to excellent yields were obtained (Table 42). In addition, the recyclability of the catalyst showed no much loss in its activity [78].


The synthesis of benzimidazole-based palladium (II)-complex 178 has been described by the reaction of benzyl derivative of 2-benzimidazolyl-oxime 177 with equimolar amount of sodium tetrachloropalladate in methanol at room temperature (Scheme 89). Also, palladium complex has benzimidazole ligand 179 which was prepared as illustrated in Scheme (90) via the reaction of equimolar amount of sodium tetrachloropalladate with ligand 176. The synthe-sized precatalyst 178 has been applied for catalysis in the Suzuki-Miyaura cross-coupling reaction of phenylboronic acids 8a and aryl and heteroaryl halides 3a and 114, respectively (Scheme 89, Table 43) [37].

4.4. Benzoxazole-based Hong et al. reported the synthesis of a novel benzoxazole-based

palladium complex 181 via cyclopalladation of the ligand 180, using palladium acetate in acetic acid under nitrogen atmosphere as shown in Scheme (91) [79].

Also, another new benzoxazole-based palladium complex 183 has been synthesized by the reaction of 2-aryl substituted naphthox-azole 182 with lithium tetrachloro palladate in methanol and in the presence of sodium acetate as a proton scavenger at ordinary tem-perature (Scheme 92) [79].

N

NH

NO

MeO

PdCl

+ BOH

OH Conditions:Cat. conc.:0.1 mol%Solvent: ionic liquid/H2OBase: K2CO3Co-catalyst:NoneTemperature: r.t.

3a-c 8 5

Ar175

X

Ar

RR

Scheme 88. Suzuki-Miyaura cross-coupling of aryl halides 3a-c and arylboronic acids 8 using complex 175 as precatalyst.

Table 42. Suzuki-Miyaura cross-coupling of aryl halides 3a-c and arylboronic acids 8 using complex 175 as precatalyst.


1 I H C6H5- 91

2 Br H C6H5- 88

3 Cl H C6H5- 84

4 I H 3,4,5-MeO3C6H2- 85

5 Br H 3,4,5-MeO3C6H2- 82

6 Cl H 3,4,5-MeO3C6H2- 79

7 I H 4-MeC6H4- 87

8 I H tBu- 70

9 I H 2-NH2C6H4- 89

10 I H 4-NO2C6H4 89

11 I H 4-MeOC6H4- 82

12 Br H 4-MeOC6H4- 80

13 I 4-MeO 2-MeC6H4- 85

14 Br 4-MeO 2-MeC6H4- 80

15 Cl 4-MeO 2-MeC6H4- 78


N

NN

CH3

O N

N

N

CH3O

N

N

N

CH3

Pd

Cl

Cl

176

177 178OH

Br

Base

Na2PdCl4

MeOH

Na2PdCl4

MeOH N

N

N

CH3OH

Pd

Cl

Cl

179

Me

Me Me

Me

161


Conditions:Cat. conc.:0.01-1 mol%Solvent: H2O Base: KOHCo-catalyst: TBABTemperature: 100 oCTime: 1-3 h

(Het) Ar+ B

OH

OH

3a or 114

5 or 115

(Het) Ar Br 178 or 179

N

N

N

CH3

OY

Pd

Cl

Cl

8a

Me

Scheme 90. Suzuki-Miyaura cross-coupling of aryl or heteroaryl halides 3a, 114 with phenylboronic acids 8a using complexes 178 or 179 as precatalyst.

Table 43. Suzuki-Miyaura cross-coupling of aryl or heteroaryl halides 3a, 114 with phenylboronic acids 8a using complexes 178 or 179 as precata-

lyst.

Yield % Entry Ar or Het

Cat 178 Cat 179

1 4-AcC6H4- 95 90

2 3-quinolinyl- 92 96

6 2-Thienyl 90 96

7 5-Acetyl-2-Thienyl 91 93

MeON

O SO3HMeO

N

O SO3H

Pd OAc

2

Pd(AcO)2

AcOH/ 100 oC

180181



NO

HO3S

N

O

PdLi2PdCl4/NaOAc

MeOH/ rtOH

O

N

O

O

182 183 Scheme 92. Synthesis of complex 183.

Conditions:Cat. conc.: 0.1 mol%Solvent: H2O Base:K3PO4Co-catalyst: noneTemperature: 100 oCTime: 4 h

+ BOH

OH

3 or 114 8a

X5

MeON

O SO3H

Pd OAc

2

R

or Het-X

R

or

Het

181

115

Scheme 93. Suzuki-Miyaura cross-coupling of aryl or heteroaryl halides 3 or 114with phenylboronic acids 8a using complex 181 as precatalyst. Table 44. Suzuki-Miyaura cross-coupling of aryl or heteroaryl hal-

ides 3 or 114 with phenylboronic acids 8a using complex 181 as precatalyst.

Entry X R or Het Yield %

1 Br H 96

2 Br Me 95

3 Br NMe2 90

4 Br Ac 96

5 Br CN 97

6 Br CF3 98

7 Br 2-Me 87

8 Br 2,6-Me2 43

9 Br 1-Naphthyl 94

10 Br 2-Pyridyl 62

11 Br 3-Pyridyl 88

12 Br 2-Thienyl 61

13 Cl 4-Me trace

14 Cl 4-Me 26a

15 Cl 4-NO2 65

a higher catalyst loading was used.

The catalytic ability of the new complex 181 was studied in Su-zuki-Miyaura cross-coupling reaction of various aryl and heteroaryl

halides 3 and 114, respectively and phenyl boronic acid 8a in water and potassium phosphate as a base (Scheme 93) [79].

The cross-coupling products were obtained in good to excellent yields in all cases regardless of the nature of the substituent in the aryl bromide 3. However, coupling with heteroaryl bromides 114, provided the products in moderate yields. In case of inactivated aryl chlorides 3c, the present catalyst 181 showed low activity for the cross-coupling even when high catalyst loading was used (Table 44). Activated aryl chlorides afforded 65% yield of the coupling product using 1 mol% of complex 181 (entry 15) [79].

5. BENZO-FUSED SIX-MEMBERED HETEROCYCLES-BASED PALLADIUM COMPLEXES

5.1. Benzopyran-Based

Synthesis of 4H-chromen-4-one-based palladium complex 185 has been reported by Kumar, S. and Ahmed, N. A via the reaction of the ligand 184 with PdCl2(PhCN)2 as shown in Scheme (94). Using this complex 185 as a precatalyst, a series of chromen-4-one derivatives 188 was obtained with excellent yields (81%-95%) by Suzuki-Miyaura cross-coupling reaction under microwave irradia-tion, using TBAB as a co-catalyst (Scheme 95) [80].

5.2. Quinoline--Based Palladium Complexes

2-Quinolinealdoxime 190 was prepared from 2-quinoline-aldehyde 189 through the condensation reaction with hydroxy-lamine as shown in scheme 96. Treatment of latter with sodium tetrachloropalladate in methanol afforded the corresponding palla-dium complex 191 at room temperature (Scheme 96) [38].

Next, the catalytic activity of the quinolone-based palladium complex 191 in aqueous Suzuki-Miyaura cross-couplings of 5-


bromobenzofuran derivative 192 with arylboronic acid 8 under microwave condition and in the presence of Cs2CO3 as a base was investigated (Scheme 97, Table 45). It was found that the cross-coupling proceeded by using catalyst complex 191 with very high TON and TOF values, and the reaction products 193 were obtained in good to excellent yields (Table 45) [38].

5.3. Phenanthroline-Based Palladium Complexes

Lutfiye et al. reported the use of phenanthroline derivatives 194 as ligand for ionic palladium complexes 195-201 with a variety of anions. Mono-palladium complexes 195-199 and poly-palladium complexes 200 and 201 were synthesized as shown in Schemes (98-100) [81].

184 185

PdCl2(PhCN)2

NN

OO

OO

Pd

NN

OO

OO

Cl Cl


Conditions:Cat. conc.:0.3 mol%Solvent: EtOHBase: K2CO3Co-catalyst:TBABTemperature:60 oC/ _wTime: 15-20 min

185

PdNN

OO

OO

Cl Cl

NH

O(HO)2B

R1

O

X

O

R2

Br+

NH

OR1

O

X

O

R2

Yield = 81-95%

X = O, NHR1 = Vinyl, Allyl , and PentylR2 = Aryl, and Furyl

186 187188

!w

Scheme 95. Suzuki-Miyaura cross-coupling of heteroaryl bromides 186 with boronic acid derivatives 187 using complex 185 as precatalyst.

N CHO

NH2OH.HCl/ K2CO3

EtOH/H2O/ ! N

NOH

N

NOH

Na2PdCl4

MeOH/ rt Pd

Cl

Cl

189 190 191 Scheme 96. Synthesis of complex 191.

N

NOH

Pd

Cl

Cl

O

Br

COOR + BOH

OH

191

O

Ar

COOR

Conditions:Cat. conc.:0.1 mol%Solvent: TolueneBase: CsCO3Co-catalyst: noneTemperature:150 oC/200 w µw Time: 23-45 min

192193

8

Ar

Scheme 97. Suzuki-Miyaura cross-couplings of 5-bromobenzofuran derivative 192 with arylboronic acid 8 under microwave condition using complex 191.


Table 45. Suzuki-Miyaura cross-couplings of 5-bromobenzofuran derivative 192 with arylboronic acid 8 under microwave condition using complex 191.

Entry R Ar µW Yield %

1 Me C6H5- 93

2 Me 4-ClC6H4- 96

3 Me 4-MeOC6H4- 87

4 Me 4-CF3C6H4- 94

5 Me 4-MeOC6H4- 85

6 Me 3,4(OCH2O)C6H3- 88

7 Me 3-Thienyl 75

8 Et C6H5- 93

9 Et 4-ClC6H4- 96

NN

Y

Pd

ClClNN

Y PdCl2(MeCN)2

DCM/ 25 oC

N

N

Y =

N

N

N

N

195

O

O N

N

N

HN

N

N

N

N

Bu

N

N

N

NH

Bu

Bu

PF6

196 197 198

194 195-199

199

Scheme 98. Synthesis of complex 195-199.

N

N

N

N

Bu

Bu

Pd

Cl

ClN

N

N

N

Bu

Bu

Pd

Cl

ClPdPd

Br

Br

Br

BrN

N

NH

N

Bu

Bu

Pd

Cl

ClPF6+

Pd(AcO)2

NaBr/ DMSO/ 80 oC

199200

Scheme 99. Conversion of complex 199 into complex 200.

N

N

N

N

Bu

Bu

Pd

Cl

ClN

N

N

N

Bu

Bu

Pd

Cl

Cl

PdPd

Br

Br

Br

Br

Pyridine

DCM/ 25 oC N

N

N

N

Bu

Bu

Pd

Cl

ClPd

Br

Br

N

200 201 Scheme 100. Conversion of complex 200 into complex 201.


Conditions:Cat. conc.:0.5 mol%Solvent: DMF/H2OBase: Cs2CO3Co-catalyst: noneTemperature:100 oC/ !Time:1 h

+ BOH

OH

3c 8a

Cl

RR

NN

Y

Pd

ClCl

5

201

Scheme 101. Suzuki-Miyaura cross-coupling reactions of various aryl chlorides 3c with phenyl boronic acid 8a using complex 201as precatalyst. Table 46. Suzuki-Miyaura cross-coupling reactions of various aryl chlorides 3c with phenyl boronic acid 8a using complex 201as precatalyst.

Entry R Yield %

1 4-Ac 76

2 2-Ac 68

3 4-Me 65

4 4-MeO 71

5 4-CHO 69

6 2-MeO 47

7 4-NO2 56

8 2,4-Me2 65

9 2,3-Me2 59

10 2,4,6-Me3 38

The catalytic activity of the synthesized phenanthroline-based

palladium complex 201 in the Suzuki-Miyaura cross-coupling reac-tions of various aryl chlorides 3c with phenylboronic acid 8 in aqueous DMF and in the presence of Cs2CO3 as a base was investi-gated (Scheme 101). A comparative study between mono-metallic 195-199 and poly-metallic complexes 200 and 201 showed nearly identical behavior in the catalysis of Suzuki-Miyaura cross-coupling reactions [81] (Table 46).

CONCLUSION

The Suzuki-Miyaura cross-coupling (SMC), has become a stan-dard procedure for various implementations, extending from phar-maceuticals to materials science. The syntheses of the valuable biaryls and substituted aromatic structures that constitute the cores of various natural products, ligands, pharmaceuticals and polymers are a target of many researchers. On the other hand, cross-coupling reactions with transition-metal-catalysts are a considerably useful synthetic route for the synthesis of biaryls via C-C bonds formation. In this review, we explored the most recent advances in the synthe-sis and the utilities of Pd-heterocyclic-complexes in the Suzuki-Miyaura cross-coupling reactions under green conditions. All cited

articles supported the view that the use of these catalysts in SMC for the synthesis of biaryls under mild conditions helps to speed up the reactions, besides they are low cost and enhanced the yields. Moreover, the newly developed catalysts showed high recyclability of more than six times without losing their activity in the coupling reactions.

CONSENT FOR PUBLICATION

Not applicable.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or oth-erwise.

ACKNOWLEDGEMENTS

All authors would like to thank Deanship of Scientific Research at Umm Al-Qura University for supporting this work (Project code: 18-SCI-5-06-0007).


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