Imine Palladacycles: Synthesis, Structural Analysis and Application in Suzuki–Miyaura Cross Coupling in Semi-Aqueous Media

Treatment of the imines a–c with palladium(II) acetate in acetic acid yielded the μ-acetate dinuclear complexes 1a–c, which readily reacted with sodium chloride or bromide to provide μ-halide analogues. The reaction of the latter with nitrogen, phosphorus and oxygen donor nucleophiles yielded new imine palladacycles following the cleavage of the Pd2X2 unit. The complexes were fully characterized by microanalysis, 1H, 13C and 31P NMR spectroscopies, as appropriate. The compounds were applied as catalysts in the Suzuki–Miyaura coupling reaction in aqueous and semi-aqueous media.


Introduction
Since the first cyclometallated compound was reported by Cope and Siekman [1], the chemistry of metallacycles dealing in the activation of aromatic C-H bonds by transition metals has attracted much attention. Their development has been extended to a rather large variety of metals, especially palladium [2], and organic ligands, among which Schiff bases, [3] thiosemicarbazones [4] and pincer ligands [5] stand out. The high level of interest in these complexes mainly stems from the high number of applications they provide, such as in metallomesogens [6], as antineoplastic substances [7,8] and in synthetic chemistry, where they have been used to functionalize aromatic carbons through the insertion reactions of molecules such as CO [9], alkenes [10] or alkynes [11]. In the field of catalysis, after the breakthrough with phosphine palladacycles by Hermann et al. [12][13][14], a myriad of palladacycles have been used as pre-catalysts in cross-coupling reactions, such as in the work of Suzuki-Miyaura [15][16][17][18][19], Mizoroki-Heck [20], Negishi [21] and Sonogashira [22]. Although there are commercially available reagents such as [Pd(OAc) 2 ] and [Pd(PPh 3 ) 4 ] that are more than acceptable catalysts, taking into account that many palladium-mediated coupling reactions involve palladacycle intermediates, palladacycles have emerged as a paramount group of catalysts owing, in part, to their stability in air and moisture.
Schiff bases, also known as imines, first prepared by H. Schiff [23] are an extensively used group of ligands, mostly due to the variety of available amines and aldehydes as well as to their ease of preparation, as they are more often than not synthesized by a condensation reaction between organic carbonyl substrate and primary amine; ketones may form imines as well, but the reaction is not so straightforward. They are able to stabilize numerous metals in different oxidation states, controlling the performance of the metals in catalytic processes. They are very suitable for the preparation of imine palladacycles, where they show a rather versatile behavior in terms of the type of metallated carbon atom, whether it be C(sp 2 ) or C(sp 3 ) ( [24]), the choice of the metallation position influenced by

Crystal Structure of 2cCl
Single crystals of complex 2cCl suitable for X-ray analysis were grown by slowly evaporating an n-hexane-chloroform solution at room temperature. The molecular structure is shown in Figure 2, and crystal data are in the Section 4 and Supplemetnary Materials.
The asymmetric unit comprises half of the molecule with a crystallographic inversion center located at the center of the Pd2(μ-Cl)2 moiety. The coordination sphere around each palladium atom consists of two halogen atoms, a C=N nitrogen atom and the C(6) carbon atom. The coordination environment at the metal center is distorted square planar, with the most noticeable deviation corresponding to the C-Pd-N bite angle of 81.29 (13).
The [(C-N)Pd(μ-Cl)2Pd(C-N)] fragment adopts a planar configuration, with an angle between the palladium coordination plane and the Pd2Cl2 ring of 6.49°. This situation is the most common configuration observed in related species [39]. All bond distances are within the expected values, with allowance for the lengthening of the Pd-X bond trans to carbon, due to the differing trans influence of the carbon and nitrogen atoms, resulting in an asymmetric Pd(μ-X)2Pd moiety. The asymmetric unit comprises half of the molecule with a crystallographic inversion center located at the center of the Pd 2 (µ-Cl) 2 moiety. The coordination sphere around each palladium atom consists of two halogen atoms, a C=N nitrogen atom and the C(6) carbon atom. The coordination environment at the metal center is distorted square planar, with the most noticeable deviation corresponding to the C-Pd-N bite angle of 81.29 (13).
The [(C-N)Pd(µ-Cl) 2 Pd(C-N)] fragment adopts a planar configuration, with an angle between the palladium coordination plane and the Pd 2 Cl 2 ring of 6.49 • . This situation is the most common configuration observed in related species [39]. All bond distances are within the expected values, with allowance for the lengthening of the Pd-X bond trans to carbon, due to the differing trans influence of the carbon and nitrogen atoms, resulting in an asymmetric Pd(µ-X) 2 Pd moiety.
The treatment of the halide-bridged complexes with the nitrogen, phosphorus or oxygen donor ligands 1,1 -bipyridine, 1,10-phenantroline, triphenylphosphine, 1,1-bis(diphenylphosphine)ethene, 1,1 -bis(diphenylphosphine)ferrocene and acetylacetonate in the appropriate molar ratio yielded the corresponding mono-and dinuclear air-stable solids, which were fully characterized (See Scheme 1 and the Experimental Section). For 4a-c the 1 H NMR spectra show singlet resonances ca. 5.3, and 2.0 and 1.9 ppm, respectively, assigned to the CH and to the two non-equivalent methyl protons, also respectively. The 1 H NMR for the phosphine derivatives showed an upfield shift in the 4-MeO group ca. 0.8 ppm promoted by the shielding of the phosphine phenyl rings; this agrees with a N-Pd-P trans geometry in 3a-b and with the parallel arrangement of the metalated moieties in 7a-b, as shown in Scheme 1, again with a phosphorus trans to nitrogen geometry. The 31 P NMR spectra showed a singlet resonance for the two equivalent 31 P nuclei in 7a-b and two doublets for 8a-b, 9b; the lower frequency doublet was assigned to the phosphorus nucleus trans to the phenyl carbon, C(6), and the higher frequency doublet to the phosphorus nucleus trans to the imine nitrogen, based on the assumption that a ligand of greater trans influence shifts the 31 P resonance in trans to lower frequency [40]. The treatment of the halide-bridged complexes with the nitrogen, phosphorus or oxygen donor ligands 1,1′-bipyridine, 1,10-phenantroline, triphenylphosphine, 1,1-bis(diphenylphosphine)ethene, 1,1′-bis(diphenylphosphine)ferrocene and acetylacetonate in the appropriate molar ratio yielded the corresponding mono-and dinuclear air-stable solids, which were fully characterized (See Scheme 1 and the Experimental Section). For 4ac the 1 H NMR spectra show singlet resonances ca. 5.3, and 2.0 and 1.9 ppm, respectively, assigned to the CH and to the two non-equivalent methyl protons, also respectively. The 1 H NMR for the phosphine derivatives showed an upfield shift in the 4-MeO group ca. 0.8 ppm promoted by the shielding of the phosphine phenyl rings; this agrees with a N-Pd-P trans geometry in 3a-b and with the parallel arrangement of the metalated moieties in 7ab, as shown in Scheme 1, again with a phosphorus trans to nitrogen geometry. The 31 P NMR spectra showed a singlet resonance for the two equivalent 31 P nuclei in 7a-b and two doublets for 8a-b, 9b; the lower frequency doublet was assigned to the phosphorus nucleus trans to the phenyl carbon, C(6), and the higher frequency doublet to the phosphorus nucleus trans to the imine nitrogen, based on the assumption that a ligand of greater trans influence shifts the 31 P resonance in trans to lower frequency [40].

Catalytic Activity
To test the catalytic activity of the new imine palladacycles depicted herein, they were probed as potential catalysts in Suzuki-Miyaura coupling (SMC) to render the corresponding biaryl species. In order to attain a clear picture of the catalytic potential of the mentioned compounds, all were tested for a standard coupling reaction in order to stablish the most efficient catalysts. Thus, the treatment of 4-bromoacetophenone with phenylboronic acid in THF:water (2:1) at room temperature (rt) or at 80 °C for a maximum of 24 h in the presence of 2 mol% catalyst and base, K2CO3, gave the biphenyl-coupled product 4-phenylacetophenone at >80% in the majority of cases ( Table 1). The use of a solvent different from the one stated above gave poorer results.

Catalytic Activity
To test the catalytic activity of the new imine palladacycles depicted herein, they were probed as potential catalysts in Suzuki-Miyaura coupling (SMC) to render the corresponding biaryl species. In order to attain a clear picture of the catalytic potential of the mentioned compounds, all were tested for a standard coupling reaction in order to stablish the most efficient catalysts. Thus, the treatment of 4-bromoacetophenone with phenylboronic acid in THF:water (2:1) at room temperature (rt) or at 80 • C for a maximum of 24 h in the presence of 2 mol% catalyst and base, K 2 CO 3 , gave the biphenyl-coupled product 4-phenylacetophenone at >80% in the majority of cases ( Table 1). The use of a solvent different from the one stated above gave poorer results.
For the experiments carried out at 80 • C (entries 1-4), the better results were obtained using THF:H 2 O or EtOH:H 2 O mixtures; even water itself gave a reasonably acceptable output (entry 3). At room temperature (entries 5-8), the solvent of choice appeared to be the EtOH:H 2 O mixture; no significant differences in conversion were observed when bases such as K 2 CO 3 or K 3 PO 4 were used. In view of the results, EtOH:H 2 O as medium and K 2 CO 3 as base were selected for further experiments, as they were the most environmentally conscious and less expensive options, respectively.  With regard to the results of this study, it can be concluded that the compounds with bpy and phen ligands, entries 22-30, in general show a much lower level of activity than the compounds tested. This may be due to the strong chelating nature of the nitrogen donor, i.e., the complex formed with the palladacycles unit is highly stable, which hinders its interaction with the substrates; this is reflected in a lower catalytic activity. In most cases the reactions at room temperature give a lower conversion than those performed at 80 °C. This is not the case for compounds with bridging chlorine and bromine ligands, entries 3-9, in which high activity is observed both at 80 °C and at room temperature, which led us to choose this type of compound as the best performers. Compounds with triphenylphosphine, entries 10 and 12, also appeared to show good results at both temperatures. As for compounds with bridging or chelating diphosphine, high conversions could be obtained at room temperature, but the reaction time had to be extended to 24 h (entries 32 and 34). Heating to 80 °C brings down the reaction time to only 5 h (entries 31,33,35,36). Some compounds with acetylacetonate ligands (entries 17-19) follow a similar pattern, but the others (entries 20, 21) gave low yields ca. 50%. We propose that the halidebridge species, which show yields of 80-100% (entries 3-9), should be singled out as the most efficient compounds as catalysts; given their straightforward synthesis and stability, they are the group of choice to carry out a more detailed study of catalytic activity, and among them we selected 2bCl, for which case the conditions for its catalytic activity could be narrowed to provide a yield of 100% at room temperature in two of the conditions tested; the results are shown in Table 2. With regard to the results of this study, it can be concluded that the compounds with bpy and phen ligands, entries 22-30, in general show a much lower level of activity than the compounds tested. This may be due to the strong chelating nature of the nitrogen donor, i.e., the complex formed with the palladacycles unit is highly stable, which hinders its interaction with the substrates; this is reflected in a lower catalytic activity. In most cases the reactions at room temperature give a lower conversion than those performed at 80 • C. This is not the case for compounds with bridging chlorine and bromine ligands, entries 3-9, in which high activity is observed both at 80 • C and at room temperature, which led us to choose this type of compound as the best performers. Compounds with triphenylphosphine, entries 10 and 12, also appeared to show good results at both temperatures. As for compounds with bridging or chelating diphosphine, high conversions could be obtained at room temperature, but the reaction time had to be extended to 24 h (entries 32 and 34). Heating to 80 • C brings down the reaction time to only 5 h (entries 31,33,35,36). Some compounds with acetylacetonate ligands (entries 17-19) follow a similar pattern, but the others (entries 20, 21) gave low yields ca. 50%. We propose that the halide-bridge species, which show yields of 80-100% (entries 3-9), should be singled out as the most efficient compounds as catalysts; given their straightforward synthesis and stability, they are the group of choice to carry out a more detailed study of catalytic activity, and among them we selected 2bCl, for which case the conditions for its catalytic activity could be narrowed to provide a yield of 100% at room temperature in two of the conditions tested; the results are shown in Table 2. Hence, under the conditions in entry 7 (Table 2), the cross couplings for the different aryl and benzyl halides with phenylboronic acid were carried out, catalyzed by compound 2bCl, as shown in Table 3. The results were satisfactory for the majority of cases. The reaction comes to completion with the different aryl bromides, having both activating (entries 6, 7 and 8) and deactivating (entry 5) groups, even at room temperature and in short reaction times. Where a chlorine atom is also present (entry 14), the coupling is selective on the bromine atom and the carbon-chlorine bond remains unchanged under the conditions indicated. The reaction was also efficient with bromide not directly bonded to the aromatic carbon (entry 9), giving rise to the coupling reaction of benzyl bromides. In the case of entries 10-13, the selectivity between aromatic bromide and benzyl bromide was studied. Treatment with an equivalent of the boronic acid to obtain the compound coupled to the aromatic carbon gave a mixture in which the desired compound was the major one, but the product coupled through the benzyl bromide was also produced in a lower proportion (entries 10 and 11). Reaction with two equivalents of the boronic acid, in the hope of preparing a doubly coupled compound, gave a mixture of products as well, i.e., 10 and 12 (entries 12 and 13). As for the coupling of aryl chlorides, in the case of starting compounds with activating groups, the reaction takes place almost quantitatively at a high temperature (entry 1), while at room temperature the product is obtained with moderate yields (entries 2-3). In the case of using deactivated chlorides such as 4-chloroanisole, the reaction hardly takes place at all (entry 4).
In order to try to optimize the reaction with 4-chloroanisole, different additional ligands were added to the reaction, such as dppf and triphenylphosphine. With the first ligand, no positive result was obtained and the inhibition of the performance of the catalyst was observed. Meanwhile, with the addition of triphenylphosphine 5% molar, the conversion of the coupling reaction increased slightly from 13% (entry 4) to 30%, but a by-product was also formed which could not be identified.
The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in 7 4 100 60/33 (7/8)

c
Molecules 2022, 27, x FOR PEER REVIEW 8 of 15 The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in 7 24 100 60/33 (7/8)

d
Molecules 2022, 27, x FOR PEER REVIEW 8 of 15 The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium ace-  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium ace-  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium ace-  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.
It can be seen that the 2bCl catalyst provides better conversions than palladium ace-  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.  The coupling reaction with chloride derivatives and 2bCl as catalyst was compared with palladium acetate, under the same conditions. The results obtained are shown in Table 4.   the catalytic activity of the catalyst; if added to palladium acetate, the yield of the re improves, which could be because it slows the formation of Pd(0) aggregates.

Conclusions
We have shown that imine palladacycles may be prepared in good yield from dium(II) acetate and the appropriate Schiff base ligand to provide μ-acetate comp which undergo metathesis reactions to yield μ-halide analogues. The latter readi dergo bridge splitting reactions to provide the corresponding mononuclear species the exception of μ-diphosphine ligands, in which case dinuclear compounds may a formed. The resulting palladacycles were tested for Suzuki-Miyaura coupling by v the reaction conditions such as the base, time and temperature, to conclude that halide complexes appeared to show the best yields. We suggest this could be due ease with which the Pd2X2 moiety may be cleaved and the halide ligand either subst or removed from the palladium coordination environment, facilitating the poten palladacycle as a pre-catalyst. Among these, the compound labelled 2bCl was th plied to the SMC of aryl halides and phenylboronic acid in different aqueous mix providing good conversions; 2bCl also showed a catalytic activity greater than the ard palladium(II) acetate under the same conditions, suggesting a promising future halide imine palladacycles as catalysts for the SMC. Also, in the light of these resul ther studies shall be conducted to determine if it is possible that other palladacyc cluded in Table 1 can be applied to the substrates in Table 3, especially with these more sterically demanding as well as bearing different +M/−M/+I/−I substituents cially if the precatalyst activation is the rate limiting step.

Experimental Section
X-ray structure determination. Crystallographic data of the structures described work were collected on a Bruker Kappa APEX II diffractometer (Mo Kα radiatio 0.71073 Å) equipped with a graphite monochromator by the method of the ω and φ at 293 K, integrated and corrected for absorption and solved and refined using r techniques. All non-hydrogen atoms were refined anisotropically; hydrogen atom included in calculated positions and refined in riding mode.
General Procedures. Solvents were used without previous purification. Che were reagent grade. The diphosphine Ph2PC(=CH2)PPh2 (vdpp) was purchased Sigma-Aldrich. Elemental analyses were carried out on a THERMO FINNIGAN, FLASH 1112. IR spectra were recorded with a JASCO FT/IR-4600 spectrometer equ with an ATR, model ATR-PRO ONE. 1 H NMR spectra in solution were recorded in or Acetone-d6 at room temperature on a Varian Inova 400 spectrometer operating at MHz. 31  It can be seen that the 2bCl catalyst provides better conversions than palladium acetate per palladium atom used. Furthermore, ligand b appears to play an important role in the catalytic activity of the catalyst; if added to palladium acetate, the yield of the reaction improves, which could be because it slows the formation of Pd(0) aggregates.

Conclusions
We have shown that imine palladacycles may be prepared in good yield from palladium(II) acetate and the appropriate Schiff base ligand to provide µ-acetate complexes, which undergo metathesis reactions to yield µ-halide analogues. The latter readily undergo bridge splitting reactions to provide the corresponding mononuclear species, with the exception of µ-diphosphine ligands, in which case dinuclear compounds may also be formed. The resulting palladacycles were tested for Suzuki-Miyaura coupling by varying the reaction conditions such as the base, time and temperature, to conclude that the µ-halide complexes appeared to show the best yields. We suggest this could be due to the ease with which the Pd 2 X 2 moiety may be cleaved and the halide ligand either substituted or removed from the palladium coordination environment, facilitating the potential of palladacycle as a pre-catalyst. Among these, the compound labelled 2bCl was then applied to the SMC of aryl halides and phenylboronic acid in different aqueous mixtures, providing good conversions; 2bCl also showed a catalytic activity greater than the standard palladium(II) acetate under the same conditions, suggesting a promising future for µ-halide imine palladacycles as catalysts for the SMC. Also, in the light of these results, further studies shall be conducted to determine if it is possible that other palladacycles included in Table 1 can be applied to the substrates in Table 3, especially with these being more sterically demanding as well as bearing different +M/−M/+I/−I substituents, especially if the precatalyst activation is the rate limiting step.

Experimental Section
X-ray structure determination. Crystallographic data of the structures described in this work were collected on a Bruker Kappa APEX II diffractometer (Mo Kα radiation, λ = 0.71073 Å) equipped with a graphite monochromator by the method of the ω and ϕ scans at 293 K, integrated and corrected for absorption and solved and refined using routine techniques. All non-hydrogen atoms were refined anisotropically; hydrogen atoms were included in calculated positions and refined in riding mode.
General Procedures. Solvents were used without previous purification. Chemicals were reagent grade. The diphosphine Ph 2 PC(=CH 2 )PPh 2 (vdpp) was purchased from Sigma-Aldrich. Elemental analyses were carried out on a THERMO FINNIGAN, model FLASH 1112. IR spectra were recorded with a JASCO FT/IR-4600 spectrometer equipped with an ATR, model ATR-PRO ONE. 1 H NMR spectra in solution were recorded in CDCl 3 or Acetone-d 6 at room temperature on a Varian Inova 400 spectrometer operating at 300.14 MHz. 31 P-{1H} NMR spectra were recorded at 202.46 MHz on a Bruker AMX 500 spectrometer. All chemical Shifts are reported downfield from standards, TMS using the solvent signal (CDCl 3 , δ 1 H = 7.26 ppm and Acetone-d 6 δ 1 H = 2.09) as reference and for 31 P relative to external H 3 PO 4 (85%). All the NMR experiments were performed using 5 mm o.d. tubes.

Preparation of the Ligands and Complexes
Preparation of a-c. 2,3,4-trimetoxybenzaldehyde (0.5 g, 2.55 mmol1 eq.) and the corresponding amine (2.55 mmol, 1 eq.) were added in water and stirred for 4 h at room temperature. The precipitate was washed with water and dried under vacuum, to give a white solid. a: Yield 85%. IR (KBr) υC=N 1633 cm −1 . 1 H NMR (CDCl 3 , 300 MHz) δ 8.55 (1H, s, HC=N Preparation of 1a-c. Ligand a-c (0.72 mmol, 1.1 eq.) and palladium acetate (0.65 mmol, 1 eq.) were introduced in a Schlenk flask and vacuum-nitrogen cycles were performed, upon which 25 cm 3 of deoxygenated acetic acid was injected with a syringe. The resulting solution was stirred at 65 • C for 8 h. Palladium (0) was removed from the mixture by centrifugation and the solution was extracted with dichloromethane and water. The organic layers were collected and dried with sodium sulphate and the solvent was removed under vacuum, resulting in a yellow solid.