Reusable Polymer-Supported Terpyridine Palladium Complex for Suzuki-Miyaura , Mizoroki-Heck , Sonogashira , and Tsuji-Trost Reaction in Water

A novel heterogeneous transition-metal catalyst comprising a polymer-supported terpyridine palladium(II) complex was prepared and found to promote the Suzuki-Miyaura, Mizoroki-Heck, Sonogashira, and Tsuji-Trost, reactions in water under aerobic conditions with a high to excellent yield. The catalyst was recovered by simple filtration and directly reused several times without loss of catalytic activity.

Heterogeneous palladium-catalyst systems have been found to be highly effective for overcoming some of these problems [16][17][18][19][20]. Heterogeneous catalysts generally comprise an organic or inorganic solid support, a linkage moiety, and a catalytic center prepared from a transition metal and a OPEN ACCESS phosphine-based ligand.Therefore, catalytic reactions are carried out under nitrogen to avoid oxidizing the phosphine ligands.We recently developed an amphiphilic polystyrene-poly(ethylene glycol) (PS-PEG) resin-supported terpyridine-metal complex and found it to be an effective catalyst for coupling reactions in water under heterogeneous and aerobic conditions with high recyclability [21,22].As an extension of that study, we investigated this catalytic utility of the PS-PEG-terpyridine-palladium(II) complex for the cross-coupling reaction in aqueous solution, with the aim to achieve more environmentally friendly reaction media.We report herein the results of these investigations and demonstrate that the complex effectively catalyzes the cross-coupling reaction in water (Scheme 1).This catalytic system offers three benefits: (1) It produces neither organic solvent waste nor metal-contaminated waste; (2) It is unharmed by oxygen and moisture; (3) It thus enables the cross-coupling reaction to meet green chemical requirements; and (4) It enables the cross-coupling reaction with high level of safety.Scheme 1. Preparation of PS-PEG resin-bound terpyridine palladium complex.

Preparation of PS-PEG Resin-Bound Terpyridine Palladium Complex
The amphiphilic PS-PEG resin-bound terpyridine ligand was prepared from p-hydroxybenzaldehyde (2), propane sultone (3), 2-acetylpyridine (5), and PS-PEG-NH 2 resin, and the coordination of the synthesized polymeric terpyridine ligand with palladium species proceeded to give the PS-PEG resin-supported terpyridine palladium complex 1, which exhibited good catalytic activity for the cross-coupling reaction.Thus, the reaction of p-hydroxybenzaldehyde (2) with propane sultone (3) in isopropyl alcohol (IPA) at 100 °C for 3 h under alkaline conditions followed by treatment of the obtained 3-(4-formylphenoxy)propane-1-sulfonic acid (4) with 2-acetylpyridine (5) and AcONH 4 in acetamide at 150 °C for 5 h gave terpyridine ligand 6 in a 68% yield in two steps.Immobilization of terpyridine ligand 6 onto an amphiphilic PS-PEG resin through ionic bonds to the sulfonate group was performed in DMF at room temperature for 1 h and the complexation of an amphiphilic PS-PEG resin-bound terpyridine ligand and Pd(II) occurred in CH 2 Cl 2 to give PS-PEG-terpyridine-Pd(II) complex 1 as a brown solid [23][24][25][26].

Sonogashira Coupling Reaction Using Polymer-Supported Terpyridine Palladium Complex
The palladium-catalyzed coupling of an aryl halide with a terminal alkyne, the so-called Sonogashira reaction, is recognized as the most successful method for forming an sp 2 carbon-sp 3 carbon bond.Since its discovery by Sonogashira and co-workers in 1975, a vast amount of research has been devoted to the synthetic application as well as the improvement of the reaction efficiency.Our continuing interest in the catalytic utility of PS-PEG-terpyridine-Pd(II) complex 1 led us to examine the Sonogashira coupling reaction in water with the PS-PEG-terpyridine-Pd(II) complex 1 under copper-free conditions.Thus, the copper-free Sonogashira coupling was examined with several haloarenes in the presence of catalyst 1 in water under aerobic conditions.The representative results are summarized in Table 3.The coupling of iodobenzene (7a) with phenylacetylene (12) took place smoothly in water at 60 °C in the presence of 3 equiv.of Et 3 N and 5 mol% palladium of the PS-PEG-terpyridine-Pd(II) complex 1 to give a 78% yield of diphenylacetylene (13a) (Table 3, entry 1).The Sonogashira coupling reaction of p-methyliodobenzene (7b) bearing electron donating groups at their para-positions gave the corresponding biarylacetylene 13b in a 65% yield (Table 3, entry 2).p-(Trifluoromethyl)iodobenzene (7d) and p-(methoxycarbonyl)iodobenzene (7l) having electron deficient aromatic rings also underwent the Sonogashira coupling with phenylacetylene under similar conditions to afford the corresponding biarylacetylenes 13c and 13d in 82% and 69% yields, respectively (Table 3, entries 3 and 4).The coupling of metaand ortho-substituted iodobenzenes 7e-g, m, n having meta-methyl, meta-chloro, ortho-methyl, and ortho-chloro groups took place with phenylacetylene to give the corresponding products 13e-i in 51%, 51%, 72%, 83%, and 76% yields, respectively (Table 3, entries 5-9).However, Bromoarene 7h in reaction with 12, carried out over longer reaction times (24 h) and at a higher temperature (100 °C), gave the corresponding stilbene 13a in a low yield (<5% yield) (Table 3, entry 11).

Tsuji-Trost Reaction Using Polymer-Supported Terpyridine Palladium Complex
The palladium-catalyzed allyl esters via π-allylpalladium intermediates, the so-called Tusji-Trost reaction, are a powerful synthetic means for forming carbon-carbon as well as carbon-nitrogen bonds.While extensive research has been devoted to the π-allylic alkylation and amination, research on π-allylic azidation has been limited to isolated reports.We also describe herein our preliminary results demonstrating that allylic azidation of several allyl esters with sodium azide proceeded in water in the presence of a polymeric catalyst 1.Thus, the coupling of allyl acetate 14a an 14b with sodium azide 15 took place smoothly in water at 70 °C in the presence of 5 mol% palladium of the PS-PEG-terpyridine-Pd(II) complex 1 to give the allyl azides 16a and 16b in 78% and 36% yields, respectively (Table 4, entries 1 and 2).The Tsuji-Trost reaction of 1-tolylallyl acetate (14c) bearing electron donating groups at their para-positions gave the 3-(p-tolyl)allyl azide (16c) in a 65% yield (Table 4, entry 3).OAc Polymers 2011, 3 629

Scheme 2.
Recycling experiments for cross-coupling reaction in water.

General Methods
All manipulations were carried out under aerobic conditions.Water was deionized with a Millipore MilliQ gradient A10 as Milli-Q grade.NMR spectra were recorded on a BURKER AVANCE spectrometer (500 MHz for 1 H and 125 MHz for 13 C) and NMR spectra were recorded on a BURKER AVANCE spectrometer (400 MHz for 1 H and 100 MHz for 13 C), and HITACHI R1900 spectrometer (90 MHz for 1 H and 22 MHz for 13 C). 1 H and 13 C NMR spectra were recorded in CDCl 3 or dimethyl sulfoxide-d 6 (DMSO-d 6 ) at 25 °C.Chemical shifts of 13 C NMR were given relative to CDCl 3 and DMSO-d 6 as an internal standard ( 77.0 ppm and 39.7 ppm).Mass spectral data were measured on a JEOL JMS-T100GCv MS detector (GC-MS) and a JEOL JMS-T100LP MS detector (LC-MS); the abbreviation 'bp' is used to denote the base peak.GC analysis was performed on a Shimadzu GC-2014.IR analysis was performed on a JASCO FTIR-410.ICP-AES spectral data were measured on a Shimadzu ICPE-9000.

Tsuji-Trost Coupling Reaction
The general procedure to obtain Tsuji-Trost reaction products 16a-d is as described here for 16a.1,3-Diphenyl-2-propenyl acetate (14a; 100 mg, 0.4 mmol) was added to a mixture of polymeric catalyst (1; 80 mg, 0.024 mmol), and sodium azide (15; 39 mg, 0.6 mmol) in H 2 O (3.0 mL).The reaction mixture was shaken at 70 °C for 24 h and then filtered.The recovered resin beads were rinsed with H 2 O and extracted three times with EtOAc (6 mL).The EtOAc layer was separated and the aqueous layer was extracted with EtOAc (3 mL).The combined EtOAc extracts were washed with brine (2 mL), dried over MgSO 4 , and concentrated in vacuo.The resulting residue was chromatographed on silica gel (hexane) to give 72.7 mg (77% yield) of 1,3-diphenyl-2-propenyl azide (16a).over MgSO 4 , and concentrated in vacuo.The resulting residue was chromatographed on silica gel (hexane) to give 57 mg (93% yield) of biphenyl (9a).After first rus, the recovered resin beads were dried in vacuo and directly applied in the next reaction under similar conditions.The reaction of iodobenzene (7a; 81 mg, 0.4 mmol) and phenylboronic acid (8a; 48 mg, 0.4 mmol) with the recovered catalyst 1 took place in K2CO3 (110 mg, 0.8 mmol) aqueous solution (3.0 mL) to give the biphenyl in 57 mg (93% yield) of biphenyl (9a).For second and third runs, these reaction conditions and procedures were also the same as first reuse procedures.

Conclusions
We developed a novel polymer-supported terpyridine palladium complex through ionic bonds to a sulfonate group, which efficiently catalyzed the Suzuki-Miyaura, Mizoroki-Heck, Sonogashira, and Tsuji-Trost, cross-coupling reactions in water under aerobic and mild reaction conditions to give the corresponding cross-coupling product with a high to excellent yield.This catalyst was recovered and reused several times without any loss of catalytic activity.Efforts to further extend the scope of the cross-coupling reactions and the application of this catalyst for other organic transformations are in progress in our lab.

Table 2 .
Mizoroki-Heck reaction using polymeric catalyst 1 in water a, b, c .

Table 4 . 18 a
Tsuji-Trost reaction using polymeric catalyst 1 in water a,b .All reactions were carried out with allyl acetate (14; 0.4 mmol) and sodium azide (15; 0.6 mmol) in the presence of the polymeric catalyst 1 in 3.0 mL of H 2 O at 70 °C for 24 h under aerobic conditions.b The 0.05 mol% of polymeric catalyst 1 (0.8 mg) was used, the reaction gave 73% yield of azide 16a (TON 1460).
a All reactions were carried out with ArX (7; 0.4 mmol), styrenes (10; 0.8 mmol), and DBU (0.8 mmol) in the presence of the polymeric catalyst 1 in 3.0 mL of H 2 O at 100 °C for 12 h under aerobic conditions.b The 0.05 mol% of polymeric catalyst 1 (0.8 mg) was used, the reaction gave 4% yield of stilbene 11g (TON 80).

Table 3 .
Sonogashira coupling reaction using polymeric catalyst 1 in water a, b .
a All reactions were carried out with ArX (7; 0.4 mmol), phenyl acetylene (12; 0.8 mmol), and Et 3 N (1.2 mmol) in the presence of the polymeric catalyst 1 in 3.0 mL of H 2 O at 60 °C for 12 h under aerobic conditions.b The 0.005 mol% of polymeric catalyst 1 (0.08 mg) was used, the reaction gave 28% yield of diphenyl acetylene 13a (TON 5600).