Catal Lett (2009) 133:262–266 DOI 10.1007/s10562-009-0181-y

Catalytic Activity of Pd(II) Complexes with Triphenylphosphito Ligands in the Sonogashira Reaction in Ionic Liquid Media I. Błaszczyk • A. M. Trzeciak • J. J. Zio´łkowski

Published online: 14 October 2009 Ó Springer Science+Business Media, LLC 2009

Abstract The reactivity of palladacycle dimeric complexes with substituted triarylphosphito ligands P(OR)3 (R = Ph, m-MeC6H4, o-MeC6H4, C6H3-2,4-tBu2) as well as their non-orthometallated analogues PdCl2[P(OR)3]2 was tested in a copper-free Sonogashira reaction with iodobenzene and phenylacetylene as substrates and imidazolium ionic liquids as the reaction medium. The ionic liquids [bmim][PF6], [bmim][BF4] and [emim][SO4Et] were chosen. The palladium complexes studied showed high activity, and the yield of diphenylacetylene ranged from 31 to 98% in 1 h. The best results were obtained in [bmim][PF6] for PdCl2[P(O-m-MeC6H4)3]2 (84%) and for orthopalladated dimer with the same phosphite (98%). Keywords Palladium
Orthometallation
Sonogashira
Ionic liquids

1 Introduction Recently the Sonogashira reaction has attracted a lot of attention as an efficient way to obtain alkenyl- and arylacetylenes, substituted alkynes, [1] symmetrical diynes, [2] conjugated oligomers and polymers, [3] materials for nonlinear optical and molecular electronics [4]. The Sonogashira coupling is a palladium-catalyzed C(sp2)–C(sp) coupling between aryl or alkenyl halides and terminal alkynes (Fig. 1) [5]. Typical substrates of the Sonogashira reaction are iodoor bromoaryl compounds, also functionalized, that react I. Błaszczyk
A. M. Trzeciak (&)
J. J. Zio´łkowski University of Wrocław, 14 F. Joliot-Curie Str., 50-383 Wrocław, Poland e-mail: [email protected]; [email protected]

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with phenylacetylene or other alkynes [1, 5–8]. Because of the air sensitivity of most catalysts, coupling reactions are performed under an inert atmosphere, often in polar organic solvents like THF, DMF, [9, 10] DMA, [3] or in water [11, 12]. Recently it has been shown that ionic liquids can also serve as good solvents in Sonogashira reactions [9, 13–18]. When 2 mol% of the palladium catalyst [(bisimidazole)2PdClMe] was used in the most frequently applied ionic liquid, [bmim][PF6], with NEt3 as a base, a yield of 85% was obtained after 2 h [6]. In Sonogashira reaction performed in a microflow system using PdCl2(PPh3)2 in [bmim][PF6] the coupling product was obtained with the yield 96, 80 and 78% in three subsequent runs [13]. The superior performance of [bmim][PF6] among the four ionic liquids screened in reaction of iodobenzene with phenylacetylene catalyzed by Pd-carbene complex was also recognized [14]. Another example is provided by the catalyst precursor PdCl2[P(OPh)3]2, which facilitates the preparation of diphenylacetylene already in room temperature with 35% yield in 1 h. Increasing the temperature to 80 °C, optimal for this reaction, made it possible to obtain 83% of the product in 4 h [15]. However, the ionic liquid should be carefully selected because ionic liquids can act as inhibitors. Such an effect has been seen with [mokt]Cl (mokt = 1-methyl-3-octyloimidazolium cation), which causes a decrease in the yield of the Sonogashira coupling and methoxycarbonylation as well [15]. Imidazolium ionic liquids were found not to be good solvents for the Sonogashira reaction catalyzed by carbapalladacycle of 4-hydroxyacetophenone oxime as a ligand [19]. Orthopalladated triarylphosphite complexes (Fig. 2) have proved to be very active catalysts in many organic reactions like Suzuki, [20–23] Stille [22] and Heck [24].

Catalytic Activity of Pd(II) Complexes with Triphenylphosphito Ligands [Pd] R X

+

H

R'

R

R'

base, -HX

X = I, Br, Cl R = aryl, vinyl R’ = aryl, alkenyl, alkyl

Fig. 1 Scheme of the Sonogashira reaction

R

1

O PR2 Pd

Cl 2

R 1a: R = t Bu; 1b: R = H; 1c: R = t Bu; 1d: R = t Bu;

R1 = iPr R 1 = Ph R1 = Ph R1 = OC6H3-2,4- t Bu

263

of 4-bromoacetophenone with styrene with TOF of up to 290,000 and TON of up to 5.75 milion [24]. Attractive catalytic properties of orthometallated palladium complexes with triarylphosphito ligands prompted us to study their activity in the Sonogashira cross-coupling in ionic liquids as the reaction media. It was expected that the results obtained would make it possible to develop an attractive catalytic system, characterized by high yield of the desired product and reasonable stability of the catalyst. Non-orthometallated complexes with the same phosphites were also tested in order to recognize the advantages, if any, of the stabilizing effect of the Pd–C bond in the metallacycle chelating ring.

2 Results and Discussion

Fig. 2 Orthopalladated Pd(II) complexes

Complexes 1a, 1b and 1c have proved to be excellent precatalysts in the Suzuki reaction for both 4-bromoacetophenone and a more challenging, electronically deactivated substrate, 4-bromoanisole. The highest TON [mol product/ mol Pd], up to nearly half a billion, was obtained when 1c was used in the Suzuki cross-coupling reaction of 4-bromoacetophenone with PhB(OH)2 [20, 22]. Similarly, complex 1d is an extremely active catalyst giving TON of up to 1,000,000 and TOFs [(mol product)/(mol Pd h)] of nearly 900,000 in the Suzuki reaction of 4-bromoacetophenone with PhB(OH)2 and TON of up to 830,000 in the Stille reaction. A mixture of 1d and PCy3 shows very good activity for the Stille coupling of aryl halides with phenyltributyltin giving 100% conversion after 18 h [22, 23]. The highest activity in the Heck reaction using 1d has been observed in the coupling

Fig. 3 Monomeric (PdCl2P2) and orthometallated Pd(II) complexes

P(OR)3

Cl Pd Cl

benzene - COD

Palladium complexes used in this work are presented in Fig. 3. The complexes PdCl2[P(OPh)3]2 (2a), PdCl2[P(Oo-MeC6H4)3]2 (2c) [25, 26] and PdCl2[P(OC6H3-2,4tBu2)3]2 (2d), [22] 3a-c [27] and 1d [22] were obtained according to the literature methods. Complex 2b was obtained by the same method as 2c. The Sonogashira reaction, without a co-catalyst, was performed using equimolar amounts of iodobenzene and phenylacetylene as substrates with NEt3 as a base. Three ionic liquids, [bmim][PF6], [bmim][BF4] and [emim] [SO4Et] (bmim = 1-butyl-3-methylimidazolium cation, emim = 1-ethyl-3-methylimidazolium cation) were used as the reaction media; selected organic solvents were also applied for comparison (Fig. 4). All the complexes selected for these studies exhibited excellent to good catalytic activity in the cross-coupling

Cl Cl

Pd

P(OR)3 P(OR)3

2 2a: R = C6H5 b: R = m-MeC6H4 c: R = o-MeC6H4 d: R = 2,4-t Bu2C6H3

PdCl2 toluene 110o C, 5h - 2HCl

OR P O

R'

OR Cl Pd

O

Pd Cl

P OR

R'

OR

3 R' = H 3a: R = C6H5 b: R = m-MeC6H4 R' = m-Me c: R = o-MeC6H4 R' = o-Me

[Pd] I

+

H NEt3 , Solvent

[Pd] = 1d, 2a - 2d, 3a - 3c

Fig. 4 Sonogashira reaction under studies ([Pd] 1 mol %; [PhI] 1 mmol; [PhC : CH] 1 mmol; [NEt3] 1.9 mmol; [IL] 1.5 mL; 80 °C; 1 h)

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I. Błaszczyk et al. 100

100

90

90

80

80

70

70

Yield [%]

Yield [%]

264

60 50 40

60 50 40

30

30

20

20

10

10

0 2a

2b

2c

2d

3a

3b

3c

1d

0 2a

2b

Catalyst Precursor [bmim][PF6 ]

[emim][SO 4Et]

[bmim][BF 4]

Fig. 5 The yield of diphenylacetylene obtained in Sonogashira reaction with different pre-catalysts and ionic liquids as reaction media in the 1st cycle

of iodobenzene with phenylacetylene in ionic liquids with NEt3 as a base (Fig. 5). The orthometallated complex 3b demonstrated the highest catalytic activity forming 98% of the product in [bmim][PF6]. Only slightly lower yield, ca. 84%, was obtained under the same conditions with complex 2b, a non-orthometallated analogue of 3b. A satisfactory result, 78%, was also obtained with complex 2a after 1 h. The same catalyst precursors were tested in two other ionic liquids, [bmim][BF4] and [emim][SO4Et], as the reaction media. The results obtained in [emim][SO4Et] were generally slightly worse than in [bmim][PF6], but for two complexes, 2c and 2d, an increase in yield was noted, to 87 and 56%, respectively. At the same time 2c gave the highest yield of diphenylacetylene in [emim][SO4Et]. The third ionic liquid tested in these studies, [bmim][BF4], appeared not to be a suitable medium for the Sonogashira reaction, giving yields of up to only 60%, which was the best result, achieved with complex 3b. The remarkable influence of the anion present in 1-butyl-3-methylimidazolium salt was seen when replacement of the PF6- anion with BF4- resulted in a decrease in yield for all of the complexes used, even by as much as 38% for 3b. The palladium(II) complexes 1d and 2d, with sterically demanding ligands, substituted with tert-butyl groups at positions 2 and 4 of the phenyl ring, exhibited the lowest yield in all three ionic liquids used. Considering the effect of ionic liquids on the yield of the Sonogashira reaction, one can conclude that [bmim][PF6] is the best one; slightly lower yields of diphenylacetylene can be obtained in [emim][SO4Et], whereas the lowest productivity was observed in [bmim][BF4]. Application of an ionic liquid as the reaction medium makes it possible to recycle the catalyst without isolating it from the reaction mixture. Figure 6 presents the yields of diphenylacetylene obtained with catalysts immobilized

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2c

2d

3a

3b

1d

Catalyst Precursor [bmim][PF6 ]

[emim][SO 4Et]

[bmim][BF 4]

Fig. 6 The yield of diphenylacetylene obtained in Sonogashira reaction with different pre-catalysts and ionic liquids as reaction media in the 2nd cycle

in ionic liquids, recovered after the first reaction. Organic products formed in the first reaction were separated by extraction with hexane, and only the ionic liquid phase was used for the second experiment. Generally, the yields obtained in the recycling experiment were 10–15% lower than in the first reaction. Such an effect can be caused by the partial deactivation of the catalyst or by its partial leaching to the hexane phase. However, the yield of diphenylacetylene in the second reaction was still satisfactory. The highest yields were achieved with 3b (88%) and 2b (69%) as precursors in [bmim][PF6]. Like in the first run, the lowest yields were obtained with complexes 1d (4%) and 2d (10%). Moreover, [bmim][BF4] again demonstrated rather unattractive properties as a reaction solvent. To learn whether ionic liquids have any positive influence on the reaction course, Sonogashira reactions were also performed in other solvents with two complexes, 2a and 3b, as catalyst precursors. Organic solvents, such as MeOH, EtOH, ethylene glycol, toluene, DMF as well as tetraalkylammonium salts, [Bu4N]Cl and [Bu4N]Br, were used. The results shown in Figs. 7 and 8 indicate that in all cases the highest yield was obtained in [bmim][PF6] as the reaction medium. In practically all reactions, the orthopalladated complex 3b was more active than the non-orthometallated complex 2a, producing, for example, 81% of the coupling product in methanol. The advantage of ionic liquids as solvents in the Sonogashira reactions studied has been clearly demonstrated; however, further mechanistic research is needed to explain these results.

3 Conclusions Palladium complexes with phosphito ligands are excellent catalyst precursors for the Sonogashira coupling

Catalytic Activity of Pd(II) Complexes with Triphenylphosphito Ligands

100 98

90 80

81 75

Yield [%]

70

67

60

60

50

49

40 30 20

22

10

To

D

M

lu e

F

ne

H eO M

][S O 4E t] [b m im ][B F Et 4] hy le ne G ly co l

Solvent

im [e m

[b m

im

][P F 6]

0

Fig. 7 The yield of diphenylacetylene obtained in Sonogashira reaction with 3b pre-catalyst in different solvents

265

(0.8 cm3) with continuous stirring. A change of color from yellow to pale yellow was observed. The solution was stirred for 45 min, after which the solvent was evaporated in vacuo and the product was recrystallized from the benzene/diethyl ether mixture. The yield of the white product was 80%. Data for complex 2b: Yield: 0.37 g (80%); elemental analysis Calcd. (%) for C42H42Cl2O6P2Pd: C 57.19, H 4.80; found: C 57.21 H 4.79; 1H NMR (500.1 MHz, CDCl3): d = 7.12 (t, 6H, H4, JH–H = 7.9 Hz); 6.98 (d, 6H, H5, JH–H = 7.6 Hz); 6.94 (d, 6H, H3, JH–H = 8.1 Hz); 6.91 (s, 6H, H1); 2.20 (s, 18H, CH3) ppm; 31P NMR (202.5 MHz, CDCl3): d = 82.66 ppm; IR(KBr)/(cm-1): 3,057, 3,020 m(= C–H); 1,587, 1,486, 1,451 m(C = C); 1,177, 1,025 m (P–O–C); 953, 788, 755, 695, 616 c(C–H). 4.2 Catalytic Reactions

100 90 80 78

Yield [%]

70

74

60 58

50 40

38

37

30 27

20 10

26

14 7

e en lu

To

H

H O Et

eO

ly

co

l M

G

ne

hy

le

Solvent

Et

[b

m

im

][B

F 4] Bu 4N C Bu l 4N Br

t] O 4E

][S im

m [e

[b

m

im

][P

F 6]

0

Fig. 8 The yield of diphenylacetylene obtained in Sonogashira reaction with 2a pre-catalyst in different solvents

of iodobenzene with phenylacetylene in ionic liquid media. Depending on reaction conditions, product yields of up to 98% were obtained. The best results were observed for the orthometallated complex 3b (98%) and its non-orthometallated analogue 2b (84%) in [bmim][PF6] as well as for 2c (87%) in [emim][SO4Et]. The application of ionic liquids also facilitated the recycling of catalysts with only a small decrease in their activity. In addition, the cross-coupling process shows high selectivity to diphenylacetylene as the only product.

4 Experimental 4.1 Syntheses (2b) PdCl2[P(O-m-MeC6H4)3]2: To PdCl2(cod) (0.15 g) in 5 cm3 of benzene was slowly added P(O-m-MeC6H4)3

The Sonogashira reactions were carried out in a Schlenk tube with magnetic stirring. Reagents: 1 mmol (0.11 cm3) of iodobenzene, 1 mmol (0.11 cm3) of phenylacetylene, 0.26 cm3 (1.9 mmol) of Et3N, an ionic liquid (1.5 cm3) or another solvent and the catalyst weighed in a small teflon vessel were introduced to the Schlenk tube under an N2 atmosphere. Next, the Schlenk tube was sealed with a rubber tap and introduced into an oil bath pre-heated to 80 °C. The reaction was carried out at 80 °C for 1 h, and after that time the Schlenk tube was cooled down and the organic products were separated by extraction with hexane (3 times with 5 cm3). The remaining palladium was removed from the hexane solution using an Al2O3 column. The extracts (10 cm3) were GC-FID analyzed (Hewlett Packard 8452A) with 0.05 cm3 of mesitylene as an internal standard. The products were identified by GC-MS (Hewlett Packard 8452A).

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