Bidentate [C,N] Schiff base ligand palladacycles: Synthesis, X-ray diffractometric analysis and survey of their catalytic activity

Palladacycles have been synthesized from Pd(OAc) 2 and Schiff base ligands via C-H activation, to render dinuclear acetate-bridged compounds. The latter are starting materials for the sequence of reactions leading to the ensuing complexes. Treatment of the µ -acetate dinuclear complexes with aqueous sodium chloride in a typical metathesis reaction, gave the corresponding µ -chloride dinuclear complexes. Reaction of the latter with triphenylphosphine or with bis(diphenylphosphino)methane (dppm) in a 1:2 ratio, and ammonium hexafluorophosphate, gave the single nuclear complexes in a bridge-splitting reaction. The compounds were characterized by microanalysis (CHN), IR and 1 H and 31 P{ 1 H} NMR spectroscopy. The crystal structures of two of them were determined by single-crystal X-ray diffraction. Additionally, the performance of the synthetized palladacycles as catalysts has been evaluated in the Suzuki-Miyaura cross-coupling reaction: they are suitable for the cross coupling of a rather large number of substrates in high yields under mild conditions.


Introduction
The chemistry of cyclometallated transition metal complexes has attracted much attention in past years since the first example appeared, 1 with those possessing five-membered metallated rings receiving the most indepth study. Numerous accounts have been undertaken regarding cyclopalladation reactions, inclusive of preparative techniques, reactivity patterns with a wide range of nucleophiles, and structural features especially in the particular case of the palladacycles bearing nitrogen donor ligands. [2][3][4][5] Palladacycle complexes with bidentate [C,N] ligands are efficient tools in catalytic methods in organic synthesis, in which novel palladacycles have shown their paramount role for the preparations; 6 Milstein et al. have developed a wide variety of imine-based palladacycles for the cross-coupling processes. 7 One of the most significant and often used methods for creating carbon-carbon bonds is the Suzuki-Miyaura cross-coupling reaction. 8,9 Although many palladium-mediated coupling reactions involve palladacycle intermediates, [10][11][12][13][14] commercially available reagent such as [Pd(OAc)2] and [Pd(Ph3P)4] are more than acceptable catalysts; nevertheless, the palladacycles have appeared as an important class of catalysts due in part to their air and water stability. Hermann et al. achieved for the first time palladacycles having a phosphorus donor atom on the metallacycle, as catalysts for the Heck and Suzuki reactions and since then many new species have been reported. 15,16 The catalytic activity of other palladacycles containing phosphine as well as halide ligands have also been investigated in the Suzuki cross-coupling. The former show a rather strong donor capability and  accepting capability. [17][18][19][20][21][22] Scheme 1. Palladacycles active as catalysts in the Suzuki cross-coupling reaction.
In previous studies, we demonstrated that functionalized imine palladacycles gave good yields in Suzuki-Miyaura coupling by modifying the reaction conditions, such as the base, time, and temperature, due to their greater simplicity in synthesis and stability. 23 Herein, we describe the synthesis and characterization of single and dinuclear palladacycles which have been tested as catalysts for the Suzuki-Miyaura cross-coupling. The compounds were characterized by microanalytical data (C, H, N), and by IR and 1 H-NMR, 31 P-{ 1 H} NMR spectroscopies. Two compounds, 3a and 4b, were also studied by X-Ray diffraction analysis. In the Suzuki cross-coupling reaction, we investigated the catalytic activity of palladacycle compounds.

Results and Discussion
For the convenience of the reader, the compounds and reactions are shown in Scheme 2. Chloroform solutions containing equimolar quantities of the corresponding aldehyde and amine were heated at reflux to give the imine ligands a and b in high yield ca. 95%. The NMR data for these ligands agreed with that in the literature. Reaction of a or b with Pd(OAc)2 yielded dinuclear cyclopalladated compounds with acetatebridging ligands 1a and 1b, respectively, with the ligand bonded to palladium(II) via the deprotonated benzylidene ortho carbon atom and the nitrogen atom from the C=N double bond. In the IR spectra, the ν(C=N) stretching vibration was shifted to lower wavenumbers in agreement with coordination of the metal via the nitrogen lone pair (1629 and 1643 cm -1 ). 24 The bridging coordination mode of the acetate ligands was confirmed by the separation of the νas(COO) and νs(COO) vibrations in the IR spectra ca. 160 cm -1 . 25 In the 1 H NMR spectra, the HC=N proton resonance was high field shifted ca. 0.9-1 ppm based on its position in the free ligand spectrum; 24 furthermore, absence of the C(6)-H resonance in the 1 H NMR spectra was indicative of metalation at the C(6) site. Treatment of compounds 1a and 1b with aqueous sodium chloride gave cyclopalladated compounds 2a and 2b, respectively, with chloride-bridging ligands (see Experimental). The IR spectra showed two ν(Pd-Cl) bands for each complex assigned to the ν(Pd-Cl)transN, (348, 320 cm -1 )and ν(Pd-Cl)transC (287, 262 cm -1 ) stretches due to the differing trans influence of the phenyl carbon atom and the nitrogen atom, confirming an asymmetric nature of the Pd2Cl2 bridging unit, and the 1 H NMR spectra confirmed the absence of the acetate ligand resonances. Single nuclear compounds were obtained by bridgesplitting reactions with monodentate (Ph3P) and bidentate (Ph2PCH2PPh2, dppm) phosphine ligands, 3a, 3b and 4a, 4b, respectively. Scheme 2. i) Pd(OAc)2, toluene, reflux; ii) NaCl (aq), acetone, 2 h; iii) Ph3P, acetone, 3 h; iv) dppm, acetone, 3 h.
The signals for the HC=N protons were a broad singlet for compound 4a and a doublet for the other compounds, indicating phosphorus nuclei coupling. The 31 P-{ 1 H} NMR spectra showed singlet, 3a, 3b, and doublet, 4a, 4b, resonances; in the latter case suggesting non-equivalent phosphorus nuclei. The assignment of the doublets was made on the assumption that a ligand of greater trans influence shifts the resonance of the phosphorus atoms trans to it to lower frequency. 26 The singlet signal of the C(4)-OMe resonance was shifted to lower field from the starting product by 0.9/0.5 ppm due to the shielding effect of the phosphine phenyl rings. The HC=N and H5 resonances showed coupling to the phosphorus nucleus trans to nitrogen singlets, 3a, 3b, and doublet of doublets, 4a, 4b, the latter also coupled to the C(4)-H proton.

X-Ray diffraction study
Crystals of 3a and 4b were grown by slowly diffusing n-hexane into a dichloromethane solution of the corresponding compound. Figures 2 and 4 illustrate the molecular structures of 3a and 4b, respectively. The structure of 3a consists of two molecules per asymmetric unit in 3a, and two molecules and a hexafluorophosphate anion in the asymmetric unit of 4b. Each structure consists of a palladium(II) atom bonded in a slightly distorted square-planar arrangement, in 3a to four different donors, a bidentate imine ligand through the aryl C(1) carbon, the imine nitrogen(1), the chloride ligand Cl(1) and the phosphorus atom P(1) of the triphenylphosphine; in 4b to a second phosphorus atom from the diphosphine ligand in place of the chloride Cl(1). The angles between adjacent atoms in the coordination sphere are close to the expected value of 90°, in the range 97.85 (5)

Catalytic activity
To investigate the catalytic activity of the new Schiff base palladacycles described in this work they were used as catalysts in the Suzuki-Miyaura reaction. Thus, treatment of 4-bromoacetophenone with phenylboronic acid in THF/water (2:1) or EtOH/water (2:1) at rt or at 80 °C for a maximum of 24 h in the presence of 2 mol % catalyst and K2CO3 as base, gave the biaryl product 4-phenylacetophenone in high yield in all cases (Table 1).  Hence, under the conditions in Table 1 the cross couplings for 4-bromoacetophenone with phenylboronic acid in aqueous THF or EtOH were satisfactory. It can be seen that the acetate-bridged compounds gave the best conversions, with the exception of the substrates bearing a p-substituted formyl group, entry 12; a similar situation was produced with the bromide-bridged dinuclear compound, entry 13. This inconvenience was overcome when using phosphine or diphosphine derivatives, giving yields > 90%, entries 14 and 15. Notwithstanding, with the o-substituted formyl moiety all compounds tested gave yields ca. 90% or greater, entries 16-19. Comparison of the results using the complexes with Ph3P or chelating dppm are much the same, albeit in complexes with the diphosphine quite high yields were obtained using a significantly shorter reaction time, entries 8 and 9. Nevertheless, the coupling reaction with the present complexes as catalysts was compared with Pd(OAc)2, entry 1, under analogous conditions. The results (Table 1) indicate better conversions for all the compounds tested than Pd(OAc)2, per palladium atom used. Attempts to use Pd(Ph3P)4 did not give yields greater than for Pd(OAc)2. Future research will deal with narrowing the gap between the possible catalysts with application of those chosen in analogous processes in the hope of producing the most suitable palladacycles for such a purpose.

Conclusions
Herein, we have shown that reaction of the corresponding imine ligands with Pd(OAc)2 produces double nuclear Schiff base palladacycles with bridging acetate ligands, [Pd(Csp2,N-imine)(µ-OAc)]2. The latter complexes are the starting point for the synthesis of the ensuing species. Thus, by a metathesis reaction of the µ-acetate palladacycles the corresponding µ-chloride analogues, [Pd(Csp2,N-imine)(µ-Cl)]2, are easily obtained. Treatment of the latter in a bridge-splitting reaction with mono-or bidentate tertiary phosphines, Ph3P and dppm, respectively, renders the single nuclear complexes [PdCl(Csp2,N-imine)(PR3)] and [Pd(Csp2,Nimine)(Ph2PCH2PPh2-P,P)(PF6)]. The molecular structures of 3a and 4b have been identified by single-crystal Xray diffraction; both display intermolecular contacts. All the compounds were applied to the Suzuki-Miyaura cross coupling reaction between a phenylboronic acid and a conveniently substituted aryl bromide in either aqueous THF or EtOH. The compounds tested gave good conversions, showing greater catalytic activity than Pd(OAc)2 under analogous conditions, ensuring a bright future for these species as potential organic solventfree catalysts towards a fully green cross coupling process.

Experimental Section
General. Solvents were purified by standard methods. 33 The reactions were carried out under dry nitrogen. Palladium(II) acetate, 4-methoxy-, 2-flourinebenzaldehydes 2-methylthioaniline, triphenylphosphine (Ph3P) and bis(diphenylphosphino)methane (Ph2PCH2PPh2, dppm) were purchased from commercial sources. Compounds a 34 and b 35 have been previously reported. Elemental analyses were performed with a Thermo Finnigan elemental analysis, model Flash 1112. IR spectra were recorded on Jasco model FT/IR-4600 spectrophotometer. 1 H NMR and spectra in solution were recorded in acetone-d6 or CDCl3 at rt on Varian Inova 400 spectrometers operating at 400 MHz using 5 mm o.d. tubes; chemical shifts, in ppm, are reported downfield relative to TMS using the solvent signal as reference (acetone-d6 δH 2.05, CDCl3 δH 7.26). Similarly, 13 C NMR { 1 H} spectra were recorded at 100 MHz on a Bruker AMX 400 spectrometer. 31 P NMR spectra in solution were recorded in acetone-d6 or CDCl3 at rt on Varian Inova 400 spectrometer operating at 162 MHz using 5 mm o.d. tubes and are reported in ppm relative to external H3PO4 (85%). Coupling constants are reported in Hz. All chemical shifts are reported downfield from standards. The ESI mass spectra were recorded using a QSTAR Elite mass spectrometer, using acetonitrile or dichloromethane/ethanol as solvents. Catalytic activity. Treatment of 4-bromoacetophenone with phenylboronic acid in THF/water (2:1) at 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 in >80% in the majority of cases ( Table 1). The use of a solvent different from the one stated above gave poorer results.