Tetradentate N 2 O 2 Chelated Palladium ( II ) Complexes : Synthesis , Characterization , and Catalytic Activity towards Mizoroki-Heck Reaction of Aryl Bromides

Four air and moisture-stable palladium(II)-Schiff base complexes, NNNNN-bis(αα-methylsalicylidene)propane-1,3-diamine palladium(II) (2a), NNNNN-bis(4-methyl-αα-methylsalicylidene)propane-1,3-diamine palladium(II) (2b), NNNNN-bis(3,5-ditert-butylsalicylidene)propane-1,3-diamine palladium(II) (2c), and NNNNN-bis(4-methoxy-salicylidene)propane-1,3-diamine palladium(II) (2d), have been successfully synthesised and characterised by CHN elemental analyses and conventional spectroscopic methods. ese complexes were investigated as catalysts in the phosphine-free Mizoroki-Heck cross-coupling reactions of aryl bromides with methyl acrylate.


Introduction
Palladium catalysed carbon-carbon coupling reactions are regarded as one of the most employed organic transformations [1,2] and have been used extensively for the agrochemical industry [3] pharmaceutical intermediates, conducting polymers, pesticides, and liquid crystals as well [4,5].Among these transformations, the coupling of aryl, vinyl, benzyl or allylic halides, acetates, or tri�ates with alkenes (via the Mizoroki-Heck reaction) is an interesting example of C-C coupling reactions in organic synthesis [6][7][8][9].ese reactions are generally carried out in the presence of palladium catalysts associated with broad structural variation such as electron rich tertiary phosphine ligands, phosphoramidites, NHCs (N-heterocyclic carbenes), diamines, P, Nand N,O-donor ligands [10][11][12][13] which could stabilize the active palladium intermediates [14,15].However, due to the difficulty to make and the high cost of phosphines in addition to their propensity to oxidize, there is a current surge in the search of alternative cheap and relatively stable phosphine-free catalysts that could offer comparable activity [16,17].erefore catalysis under phosphine-free conditions represents a challenge of high importance.
e development of simple, mild, efficient, and more ecologically friendly applications has become a common goal for many researchers [18].Among the later, Schiff bases have been extensively studied and proved suitable for palladium species.In our attempt to evaluate the phosphine-free system in the Mizoroki-Heck reaction, N 2 O 2 -tetradentate Schiff base ligand was chosen.N 2 O 2 -tetradentate ligands possess many advantages such as facile approach, readily adjusted ancillary ligand, and electronic environments on the metal centre [19].Active and well-de�ned Schiff base metals complexes have been widely studied due to the versatility of their steric and electronic properties, which can be �ne-tuned by choosing the amine precursors and ring substituents [20,21].Due to these properties, N 2 O 2 -tetradentate ligands and their transition metal complexes oen act as catalyst.

Experimental
All reactions were carried out under an inert atmosphere of dry nitrogen.Commercial grade solvents were distilled according to normal procedures and dried over molecular sieves (4 Å) prior to use.All reagents were obtained commercially and were used without further puri�cation.e melting points were measured in capillary tubes using a Electrothermal Digital Melting Point Apparatus and were uncorrected.IR spectra were recorded as KBr matrix on a Perkin Elmer Spectrum One FTIR spectrometer in the range of 4000-400 cm −1 .NMR spectra were recorded in CDCl 3 on a Bruker Avance 400 MHz spectrometer operating at the appropriate frequencies.e chemical shis are reported in ppm using tetramethylsilane (TMS) as internal standard.Elemental analyses were performed on a ermo Finnigan CE 125 CHN analyzer.
Gas chromatography (GC) analyses were carried out on a GC-Hewlett-Packard 5890 series II gas chromatograph equipped with a 30 m × 250 m × 0.25 m nominal capillary column (ULTRA-1.0.05, 100% dimethylpolysiloxane) and Flame Ionization Detector (FID).e microliter samples are injected at 50 ∘ C. e temperature increment is at 15 ∘ C per minute and the �nal temperature was 300 ∘ C.

Synthesis of the Palladium(II)
Complexes 2a-2d.All Pd(II) complexes were synthesized following the standard methods [23,[27][28][29].e complex 2c was prepared by treating an equivalent molar amount of the corresponding ligand with Pd(OAc) 2 in acetonitrile.e spectroscopic data ( 1 H, 13 C NMR, and FTIR) of this complex are in agreement with those reported recently by Ulusoy et al. [30].
palladium complex 2b was prepared and isolated as brown solid in 75% yield aer treating palladium(II) acetate with one mole equivalent of ligand 1b in a similar manner to the method described for 2a.palladium(II) complexes 2a-2d were prepared under nitrogen atmosphere as shown in Scheme 2. e reaction of palladium(II) acetate with the appropriate Schiff base proceeds smoothly in re�uxing acetonitrile, to give the brownish complexes 2a (77%), 2b (75%), 2c (78%), and 2d (80%).All the ligands and the palladium(II) complexes were fully characterised.Elemental analytical, FTIR, 1 H, and 13 C NMR data are given in the Experimental section.Microanalytical data for the ligands and the palladium complexes are consistent with the calculated empirical formula values.

Results and Discussion
e FTIR spectra of the Schiff bases 1a-d, each showed the appearance of a very strong azomethine (C=N) stretching band at 1615, 1611, 1633, and 1622 cm −1 , respectively.ese values are consistent and are in agreement with other similar imine compounds [32].Besides that, the absorption bands for the (-NH 2 ) stretching mode from 1,3diaminopropane and the (C=O) stretching mode from 2-hydroxyacetophenone, 2-hydroxy-4-methylacetophenone, 3,5-di-tert-butyl-2-hydroxybenzaldehyde, and 2-hydroxy-4methoxybenzaldehyde have totally disappeared, demonstrating that in each case, the condensation is complete, con�rming that the ligands have been successfully synthesized.
Meanwhile, the IR spectra of the palladium(II) complexes 2a-d, each exhibit a strong and sharp (C=N) stretching band at 1597, 1607, 1613, and 1606 cm −1 , respectively.e slight displacement of the (C=N) band from 1615, 1611, 1633, and 1622 cm −1 in the free ligands suggested the coordination of the azomethine nitrogen atoms to the palladium metal in the complexes.is results show that the contribution of the C=N stretching have been reduced as the nitrogen atoms are involved in bond formation with the metal ion.Besides, the broad (O-H) band at 3445, 3436, 3426, and 3432 cm −1 in the ligands 1a-d, respectively, are absent in the IR spectrum of the complexes, suggesting the deprotonation of the O-H groups and subsequent coordination of the phenolic oxygen atoms to the metal centre.
e NMR spectra of the complexes further supported the assigned structures.e signal of the acidic OH proton for 1a-d in the 1 H NMR spectra of the free ligands, each appeared as single resonance at low �eld at  12.28, 12.30, 13.81, and 13.90 ppm, respectively.ese signals have totally disappeared in the 1 H spectra of the complexes, indicating the coordination of the phenolic oxygen atoms to the palladium metal due to the participation of OH groups in chelating to metal ion through proton displacement [33].Meanwhile, the 13 C NMR spectral data showed the displacement to low �eld of the imine carbon (C=N) resonance from  172.4,172.0, 166.5, and 163.6 ppm for 1a-d in the free ligands to  169.2, 168.8, 163.8, and 161.3 ppm, respectively in the complexes which further support the coordination of the azomethine nitrogen atoms to the palladium metal.

Catalytic
Studies.e palladium complexes 2a-d were tested as catalysts for the Heck coupling reaction of methyl acrylate with 4-bromoacetophenone. e reactions were carried out under nitrogen atmosphere in DMA in the presence of base at 120 ∘ C (Scheme 3).4-bromoacetophenone is chosen as it is economical and more readily available substrate.Owing to the stability and commercial availability of this aryl bromide, the development of a general procedure for the direct coupling of inexpensive aryl bromide with methyl acrylate still represents a challenging and important goal in coupling chemistry [34].e use of this electron-de�cient bromide was also bene�cial for the conversion as well [35].In addition, methyl acrylate has been chosen as the only ole�n investigated in this study because the resulting cinnamic ester derivatives are usually used as UV absorbers [36], as antioxidants in plastics, and as intermediates for pharmaceuticals [37].
All the complexes were found to catalyse the coupling of methyl acrylate with 4-bromoacetophenone to form exclusively trans-acid methyl ester as established by 1 H NMR analysis.No other coupling products (cis or gem-isomers) were observed.is is in agreement with previous studies by Ojwach et al. [17] and Yasar et al. [35] which reported that in all cases only the trans products were selectively obtained as con�rmed by 1 H NMR spectroscopy.
Our initial exploration of reaction conditions focused on the effect of bases.e results are shown in Table 1.Catalytic loading was kept to 1.0 mmol%, so as to give an expected turnover number of 100 if 100% conversion was achieved.e main function of base in the Heck crosscoupling reaction mechanism is to neutralize the acidic condition of hydrogen halide in the reductive elimination step and regeneration of catalyst to continue the catalytic cycle [16].Aer screening a variety of bases, NaOAc was found to be most effective base as highest conversion was obtained (entries 7, 22, and 23).In contrast, low conversion was achieved when using Na 2 CO 3 (entries 12 and 26), probably due to the insolubility of Na 2 CO 3 .
In the case of an organic base, low conversion was also observed for Et 3 N (entries 1 and 17) which may due in part to steric effects exerted by competitive coordination of amine to palladium center [38,39].It may also in part due to the formation of gaseous Et 3 N at 120 ∘ C that may lead to poor contact with the reaction mixture.Complex 2c showed slightly better catalytic performance than complexed 2a, 2b, and 2d probably due the presence of the electron donating 3,5-di-tert-butyl group.In addition, the bulkier ligands are also believed to accelerate the oxidative addition of aryl bromides under homogeneous conditions [30].Hence, our further investigations only focussed on the catalytic performance of 2c.
e effect of catalyst loading on the performance of the Heck coupling reactions using catalyst 2c was then examined (Table 2).e yield of Heck products normally depended on the amounts of Pd(II) catalyst used.e Pd catalysts are important in the oxidative addition and the alkene insertion steps which were the rate-determining steps in the Heck cross-coupling reactions [40].By controlling the amount of Pd catalyst (mmol%), higher turnover number (TON) can be achieved to maximize the percentage conversion of the desired products.
As shown in Table 2, it is apparent that the highest TON value of 200 (entry 2) was achieved even at low catalyst loading (0.5 mmol%).ere is considerable activity with a conversion of 100% aer 6 hours of reaction time.us, we conclude that the choice of 0.5 mmol% Pd-catalyst loading is suitable since it can give higher TON at the same reaction time.
Having established the optimum catalytic conditions, using NaOAc as a base and with 0.5 mmol% catalyst loading, the performance of catalyst 2c was further screened at different reaction temperatures (Table 3).It is well known that the reaction temperature has a very strong in�uence on Heck cross-coupling reaction [41].However, reaction temperature must be carefully controlled to avoid the formation of palladium black which will inhibit the catalytic cycle if the temperature is too high [42].From our studies, the optimum reaction temperature was found to be at 120 ∘ C which is suitable for the activation of aryl bromide (entry 4).e catalytic data obtained indicated that complex 2c efficiently catalyse the Heck cross-coupling reaction of 4-bromoacetophenone with methyl acrylate, giving 100% conversion aer 6 hours.Under the optimisation reaction conditions, several of aryl bromides were tested with methyl acrylate (Table 4), affording the coupled products occurred in excellent yields.As expected, the results showed that the electron-de�cient bromides (entries 1 and 2) were bene�cial for the conversions.Attempts had been made to use an electron-donating bromide (entry 3) and electron neutral bromide (entry 4).However no conversions were achieved and no desirable coupled products were obtained.It is noted that the percentage of conversion observed for the amino substituted compound is signi�cantly high (entry 2).Although the NH 2 group can also acts as electron donor through resonance, it is believed that the electron withdrawing effect of the electronegative nitrogen atom is more dominant in stabilising the electron rich reaction intermediates.
As stated above, the catalytic activity of palladium complex 2c was found to be active and efficient catalyst for Heck cross-coupling reaction involving electron de�cient aryl bromides with methyl acrylate in which under optimised reaction conditions, excellent conversion of coupled products could be obtained.It should be noted that in all cases only the trans products were selectively obtained as con�rmed by 1 H NMR.
e application of aryl chlorides as substrates in the Mizoroki-Heck reactions is arguably most attractive due to their higher availability.However, the palladium-catalysed couplings of aryl chlorides were very uncommon and not favourable due to their low reactivity which has usually been attributed to the reluctance of the aryl chloride bond to undergo oxidative addition to Pd(0) [43].It has been reported that treatment of aryl chlorides with alkenes resulted in low conversion of products formation and it was known that the oxidative addition of aryl chlorides can only be achieved at elevated temperatures [44,45].
3.1.Synthesis of Ligands and Palladium(II) Complexes.eSchiffbase ligands 1a-1d were synthesised by condensation reaction between 1,3-diaminopropane with 2 mole equivalent of the corresponding carbonyl compounds according to the step shown in Scheme 1. e condensation reactions were rapid and complete.Meanwhile, the corresponding T 1: Effect of the base on the catalytic performance a .
bDetermined by GC-FID.c Turnover number (TON): moles of substrate converted per mole of metal in the catalyst.

T 2 :
Effect of the amount of catalyst on the catalytic performance a .
T 4: Effect of substituted aryl bromides on the catalytic performance a .
bDetermined by GC-FID.c Turnover number (TON): moles of substrate converted per mole of metal in the catalyst.