Phosphine-Free Tetradentate Salicylaldimine Ligand Complexed with Palladium: First Application in Heck Reactions

Abstract Heck reactions were carried out using phosphine-free tetradentate salicylaldimine ligand complexed with PdCl2 under mild reaction conditions, short reaction time, and low palladium loading. All aryl iodides underwent coupling reactions with olefins, giving corresponding trans-products, with good to excellent yields, whereas aryl bromides gave very poor yields and aryl chlorides failed to react. GRAPHICAL ABSTRACT


INTRODUCTION
Because of their high potential for useful features such as enhanced performance over mononuclear complexes, ability to combine the best properties of homogeneous and heterogeneous catalysts in one system, and stable macromolecular structures that make them suitable for isolation via ultrafiltration and thus provide potential for catalyst recycling, [1] dendrimeric ligand-based metal catalysts (metallodendrimers) have recently attracted attention. Their exploitation is mainly aimed at reducing the amount of Pd required and high performance of the catalysts. Reactions catalyzed by using metallodendrimers include the Heck reaction, [2] Suzuki-Miyaura reaction, [3a] oxidation, [3b,c] polymerization, [1a,b] Sonogashira reaction, [4] hydroformylation, C-C coupling metathesis, [3d,5] and epoxide ring opening. [6] The Heck reaction, a widely used reaction in synthesis of various substituted olefins, dienes, and natural products, is one of the most important palladiumcatalyzed reactions in organic chemistry for which several homogeneous and heterogeneous protocols have been reported in literature. [7,8] Most of the reported protocols employ Pd, an expensive metal, as catalyst in relatively large amounts and use of these large amount also results in residual metals in the products, creating environmental concerns. [8a,b] Ligands play an important role in the Heck reaction by increasing the solubility of metal, minimizing the palladium loading, and yielding catalysts with high turnover number and high reactivity. [8c] In this context dendritic ligands have received attention. A few examples are Reetz's dendritic phosphine, DAB-dendr-[N(CH 2 PPh 2 ) 2 ] 16 , bearing P-centers on the periphery coordinated to Pd catalysts, [9] DAB-G1(impyr-PdCl 2 ) 4 catalyst, [2] Pd(II)-phosphine complexes modified poly(ether imine) PETIM dendrimers, [10] palladium nanoparticle cored G3 dendrimer, [11] iminophosphine DAB-dendr-[1,2-(NCHC 6 H 4 PPh 2 )] 32 , DAB-32imiphos, and corresponding aminophosphine, DAB-dendr-[1,2-(NHCH 2 -C 6 H 4 PPh 2 )] 32 , DAB-32-amiphos, i.e., two dendrimeric P, N-ligands, [12] G4 PAMAM dendrimer encapsulated Pd 0 nanoparticles, [13] dendritic nanoreactor prepared by incorporating Pd 0 nanoparticles into poly(propylene imine) (PPI) dendrimer, and PPI dendrimer covalently functionalized with perfluorinated polyether chains on the periphery. [14] G1 and G2 dendrimeric salicylaldimine ligands based on PPI dendrimer scaffolds have been synthesized for preparation of multinuclear nickel complexes and evaluated in polymerization of norbornene. [1a] However, these ligands have not been used so far for preparation of Pd complexes and screened   4 ], successfully prepared the Pd(II) complex 1 (Fig. 1), and employed it for Heck coupling reactions.

RESULTS AND DISCUSSION
DAB-dendr-[1,2-N=CH-C 6 H 4 -OH] 4 Pd (II) complex 1, having two catalytic sites, was prepared by using PdCl 2 (CH 3 CN) 2 and refluxing in CH 3 CN for 24 h to ensure the completion of the reaction. The infrared (IR) spectra of 1 showed shifts in n (C = N) and n (C-O) stretching frequencies from 1627 and 1275 cm À1 to 1621 and 1313 cm À1 respectively, ensuring the formation of the complex, and mass spectrometry and elemental analysis confirmed the molecular formula.
Previously, dendrimers with 2 to 60 Pd atoms have been prepared either by complexation or entrapment. [2,10,11,13] Two Pd atoms were complexed with G1 PETIM dendrimer [10] but in the form of phosphine ligand. For the first time we complexed two Pd atoms with tetradentate DAB-dendr-[1,2-N = CH-C 6 H 4 -OH] 4 ligand without any phosphine. Phosphine-free conditions for Pd-catalyzed reactions are preferred because of adverse environmental effects associated with phosphines. [12] Heck coupling reactions between iodobenzene and methyl acrylate as model substrates were attempted using 1 and the results are summarized in Table 1. Reactions were carried out in different solvents such as toluene, CH 3 CN, acetone, acetone-water (1:1), water, and dimethylformamide (DMF) with 1 mol% of 1 and K 2 CO 3 as a base and at different temperatures. Reaction did not proceed in acetone, acetone-water (1:1) mixture, or water (entries 4-6, Table 1), whereas in toluene and CH 3 CN the reaction did proceed but gave poor yields (10-17%) (entries 1-3, Table 1). The best results were obtained in DMF and at reaction temperature of 80 C, giving very good yield in 4 h (entry 8, Table 1). Amount of 1 was reduced up to 0.1 mol%, keeping the other reaction conditions the same, and we noticed no significant change in yield (entry 10, Table 1). Therefore for further studies DMF was chosen as solvent with catalyst amount of 0.1 mol% and reaction temperature of 80 C.
To study the scope of the methodology, reactions were carried out using different substrates, and results are presented in Table 2. All of the olefins gave good to excellent yields except acrylamide (entry 8, Table 2), which did not show any reaction. In all cases only trans isomer was obtained and none of the cis isomer or any other by-product could be observed by thin-layer chromatography (TLC) or 1 H NMR spectra. In the case of acrylic acid esters it was noticed that going from methyl to t-butyl esters resulted in a slight decrease in yield (entries 3-6, Table 2). Styrene also reacted well but yield was comparatively less (entry 7, Table 2). Failure of acrylamide to react (entry 8, Table 2) was attributed to deactivation of catalyst by complexation with amide group. This conclusion is supported by carrying out reactions with methyl acrylate in the presence of acrylamide and acetamide and in both the cases the reaction did not proceed. Reactions with p-chloroiodobenzene and pmethyliodobenzene were equally facile but slightly lower yields were obtained with p-methyl-compared to p-chloroiodobenzenes (entries 9-12, Table 2).
Attempts to carry out the reaction on aryl chlorides were unsuccessful whereas reaction with aryl bromides gave poor yields (entries 13 and 14, Table 2). A control reaction using only equivalent amounts of PdCl 2 as catalyst with no ligand gave <3% yield. To assess the standing of 1 with respect to other metallodendrimers, literature data is compiled in Table 3. Metallodendrimers with palladium loading in the range of 0.2 to 8 mol% have been used for 5 mmol of iodobenzene in evaluating Heck reactions, whereas in our case 0.2 mol % of Pd loading was sufficient to give almost the same yield as that of the best catalyst but in shorter time (entry 1 and 5, Table 3), showing the superiority of 1.

In conclusion we have developed a new phosphine-free tetradentate palladium complex [DAB-dendr-[1,2-N=CH-C 6 H 4 -OH] 4 ] [PdCl 2 ] 2 for efficient Heck reaction.
The catalyst is superior because less Pd is required to achieve the same yield under similar reaction conditions in comparison with known methods utilizing metallodendrimers.
EXPERIMENTAL Bis(acetonitrile)dichloropalladium (II), 1,4-diaminobutane, and iodobenzene were obtained from Aldrich and used as received. All other chemicals were purchased from local chemical suppliers and used without any purification. IR spectra were recorded on a FT-IR RX1 Perkin-Elmer instrument. 1 H NMR spectra were recorded on a Jeol MY-60 instrument operating at 60 MHz. Chemical shifts are given as parts per million (ppm) downfield from tetramethylsilane (TMS) in d units. Electrospray ionization (ESI)-mass spectra (MS) was recorded using an Agilent 6524 Q-TOF Mass LC MS=MS system (Agilent, USA). Melting points were determined 3340 R. S. KALHAPURE, T. GOVENDER, AND K. G. AKAMANCHI with a Veego melting-point apparatus having a stirred paraffin bath. Silica gel (60-120 mesh) was used for column chromatography and thin-layer chromatography (TLC) was performed using Merck silica-gel 60 F254 plates.
Reaction mixture was filtered through a bed of celite to remove Raney nickel and the filtrate was concentrated under vacuum. The crude product obtained was dissolved in dry acetone and filtered to remove NaOH. The acetone layer was concentrated in vacuo to get the colorless oil (20.44 g, 97%). This G1 PPI was used without further purification.

General Procedure for Heck Reaction
Aryl halide (5 mmol), olefin (10 mmol), K 2 CO 3 (5 mmol), and 1 (0.1 mol%) were taken in DMF (10 mL) in a sealed tube (25 mL) fitted with a Teflon cap under N 2 atmosphere and the mixture was heated with stirring at 80 C for 4 h and cooled to room temperature. The solvent was evaporated under reduced pressure on a rotary evaporator. The residue was extracted using EtOAc (3 Â 10 mL) and dried over Na 2 SO 4 , and the solvent was removed on a rotary evaporator. The crude residue obtained was purified by column chromatography on silica gel, 60-120 mesh (petroleum ether-EtOAc, 98:2).

FUNDING
Rahul S. Kalhapure is thankful to the University Grants Commission (UGC), Government of India, and the National Research Foundation of South Africa for financial support.

SUPPORTING INFORMATION
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