Organo-palladium(II) complexes bearing unsymmetrical N,N,N-pincer ligands: synthesis, structures and oxidatively induced coupling reactions†

The 2-(2’-aniline)-6-imine-pyridines, 2-(C6H4-2’-NH2)-6-(CMevNAr)C5H3N (Ar = 4-i-PrC6H4 (HL1a), 2,6-i-Pr2C6H3 (HL1b)), have been synthesised via sequential Stille cross-coupling, deprotection and condensation steps from 6-tributylstannyl-2-(2-methyl-1,3-dioxolan-2-yl)pyridine and 2-bromonitrobenzene. The palladium(II) acetate N,N,N-pincer complexes, [{2-(C6H4-2’-NH)-6-(CMevNAr)C5H3N}Pd(OAc)] (Ar = 4-i-PrC6H4 (1a), 2,6-i-Pr2C6H3 (1b)), can be prepared by reacting HL1 with Pd(OAc)2 or, in the case of 1a, more conveniently by the template reaction of ketone 2-(C6H4-2’-NH2)-6-(CMevO)C5H3N, Pd(OAc)2 and 4-isopropylaniline; ready conversion of 1 to their chloride analogues, [{2-(C6H4-2’NH)-6-(CMevNAr)C5H3N}PdCl] (Ar = 4-i-PrC6H4 (2a), 2,6-i-Pr2C6H3 (2b)), has been demonstrated. The phenyl-containing complexes, [{2-(C6H4-2’-NH)-6-(CMevNAr)C5H3N}PdPh] (Ar = 4-i-PrC6H4 (3a), 2,6i-Pr2C6H3 (3b)), can be obtained by treating HL1 with (PPh3)2PdPh(Br) in the presence of NaH or with regard to 3a, by the salt elimination reaction of 2awith phenyllithium. Reaction of 2awith silver tetrafluoroborate or triflate in the presence of acetonitrile allows access to cationic [{2-(C6H4-2’-NH)-6-(CMev N(4-i-PrC6H4)C5H3N}Pd(NCMe)][X] (X = BF4 (4), X = O3SCF3 (5)), respectively; the pyridine analogue of 5, [{2-(C6H4-2’-NH)-6-(CMevN(4-i-PrC6H4)C5H3N}Pd(NC5H5)][O3SCF3] (5’), is also reported. Oxidation of phenyl-containing 3a with one equivalent of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) (SelectfluorTM) in acetonitrile at low temperature leads to a new palladium species that slowly decomposes to give 4 and biphenyl; biphenyl formation is also observed upon reaction of 3a with XeF2. However, no such oxidatively induced coupling occurs when using 3b. Single crystal X-ray diffraction studies have been performed on HL1b, 1a, 1b, 2a, 2b, 3a, 3b and 5’.


Introduction
Recent years have seen a surge of interest in oxidatively induced coupling reactions involving Pd(III) and Pd(IV) intermediates due, in part, to their potential to promote transformations inaccessible using the conventional low valent Pd(0)/(II) cycle. [1][2][3] For example, the historically challenging arene-fluoride bond forming reaction has become a reality with both types of high valent intermediate isolated and/or proposed in reaction pathways derived from Pd(II) species. 3 Central to these developments have been reagents such as Selectfluor™ [1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis-(tetrafluoroborate)] and xenon difluoride that can oxidise the metal centre as a two electron oxidant (from Pd(II) to Pd(IV)) 4,5 or as a one electron oxidant (from Pd(II) to Pd(III)) 6,7 and moreover provide a source of F (e.g., as F + or F • ). In cases where these types of oxidant deliver a fluorine atom direct to the metal centre, selective C-F reductive elimination from the high valent organo-metal intermediate can be challenging as alternative (and potentially desirable) degradation pathways can prove competitive. 3d Sanford, for example, has reported that the Pd(IV) mono-aryl complex, [(4,4-t-Bu 2 bipy)Pd(Ar)-(F) 2 (FHF)] (Ar = 4-FC 6 H 4 ), only undergoes selective C aryl -F reductive elimination when heated in the presence of excess oxidant, otherwise competitive Ar-Ar coupling occurs through a process described as σ-aryl exchange between metal centres. 5 Indeed this type of intermolecular Ar-Ar coupling involving palladium mono-aryl species has some precedent in Pd(II) and Pd(III) chemistry involving complexes bearing a variety of multidentate ligands. 2c,8,9 Given the apparent variation in coupling events that can occur from a high valent organo-Pd species, 1-7 we have been interested in exploring the influence of a supporting multidentate ligand on the oxidatively induced reaction pathway. Herein, we report the reactivity of a family of N,N,N-pincer bearing Pd(II) mono-phenyl complexes of the type, [{2-(C 6 H 4 -2-NH)-6-(CMevNAr)C 5 H 3 N}PdPh] (Ar = aryl (3)), towards Selectfluor and XeF 2 (Fig. 1); 10 as an additional point of interest the effects that steric variation (Ar = 4-i-PrC 6 H 4 , 2,6-i-Pr 2 C 6 H 3 ) has on the reactivity, will be investigated. Furthermore, we report the full synthetic details for the preparation of the novel pro-ligands (HL1) and their palladium(II) acetate (1), chloride (2) and phenyl (3) derivatives.
Compounds, HL1a, and HL1b, both display protonated molecular ions peaks in their electrospray mass spectra and downfield shifted signals for the amino protons (range: δ 5.72-5.79) in their 1 H NMR spectra. Characteristic imine stretching frequencies of ca. 1638 cm −1 are seen in their IR spectra as are higher wavenumber bands corresponding to the N-H stretches. Further confirmation of the composition of HL1b was achieved in the form of a single crystal X-ray determination.
A perspective view of HL1b is depicted in Fig. 2; selected bond distances and angles are listed in Table 1. The structure consists of a central pyridine ring that is substituted at its 2-position by a phenyl-2′-amine group and at the 6-position by a trans-configured N-arylimine unit [C(7)-N(1) 1.277(3) Å]. The pyridine nitrogen atoms adopt a cis conformation with respect to the neighbouring aniline nitrogen (tors: N(2)-C(13)-C(14)-C(15) 8.1°) as a result of a hydrogen-bonding interaction between one of the amino hydrogen atoms and the pyridine nitrogen [N(3)⋯N(2) 2.675 Å]; a similar arrangement has been reported for a related quinolinyl-substituted aniline. 11

Palladium(II) complexes of L1
Interaction of HL1b with Pd(OAc) 2 at 60°C in toluene gave on work-up, [{2-(C 6 H 4 -2-NH)-6-(CMevN(2,6-i-Pr 2 C 6 H 3 ))C 5 H 3 N}Pd-(OAc)] (1b)), in good yield (Scheme 2). While [{2-(C 6 H 4 -2-NH)-6-(CMevN(4-i-PrC 6 H 4 ))C 5 H 3 N}Pd(OAc)] (1a) could also be made by this route, it was more conveniently prepared by the template reaction of ketone 2-(C 6 H 4 -2-NH 2 )-6-(CMevO)C 5 H 3 N, Pd(OAc) 2 and 4-isopropylaniline. Compounds 1 can be readily converted to their chloride analogues, [{2-(C 6 H 4 -2-NH)-6-(CMevNAr)C 5 H 3 N}PdCl] (Ar = 4-i-PrC 6 H 4 (2a), 2,6-i-Pr 2 C 6 H 3 (2b)), by treatment of a dichloromethane solution of 1 with aqueous sodium chloride. All four complexes are air stable and have been characterised using a combination of FAB mass spectrometry, IR and NMR ( 1 H and 13 C) spectroscopy and elemental analyses (see Experimental section). In addition, crystals of each complex have been the subject of single crystal X-ray diffraction studies. Views of acetate-containing 1a and 1b are given in Fig. 3 and 4; selected bond distances and angles are collected for both structures in Table 2. There are two independent molecules for 1b in the unit cell (A and B) which differ most noticeably in the relative inclination of neighbouring pyridyl and anilido ring planes (vide infra). The structures of 1a and 1b are similar consisting of a four-coordinate palladium centre bound by a tridentate monoanionic 2-(2′-anilido)-6-imine-pyridine ligand and a monodentate O-bound acetate, but contrast in the nature of the hydrogen bonding involving the acetate ligand. In 1a, a water molecule present within the unit cell links the palladium-acetate units to form a hydrogen-bonded network [O(1) acetate ⋯O(3) water 2.837, O(3) water ⋯O(2A) acetate 2.877 Å], while in 1b the hydrogen bonding is intramolecular in origin involving the pendant acetate oxygen and the anilido proton [N(3)⋯O(2) acetate 2.799 A , 2.889 B Å]. Within the N,N,Nligand there are both 5-and 6-membered chelate rings with the bite angle for the 6-membered ring being more compatible with the square planar geometrical requirements of the palladium(II) centre [N(3)-Pd(1)-N(2) 6-membered : 93.7(2) (1a), 92.2(3) A , 93.6(2) B (1b) vs. N(2)-Pd(1)-N(1) 5-membered 82.2(2) (1a), 82.6(3) A , 82.1(2) B°( 1b)]. In both cases some twisting of the anilido unit with respect to the adjacent pyridyl plane is apparent [tors. N(2)-C(13)-C(14)-C(15) 3.6(4) (1a), 4.9(4) A , 9.0(5) B°( 1b)]. For a given complex, the Pd-N imine bond distance is the longest of the three metal-ligand interactions involving the N,N,N-ligand followed by the Pd-N pyridine distance and then by the Pd-N anilido distance which is best exemplified for 1a    , which display similar bonding characteristics. 12 A view of chloride-containing 2b is given in Fig. 5; selected bond distances and angles are collected for both 2a and 2b in Table 3. The two independent molecules present in the unit cell for 2a (A and B) differ most noticeably in the inclination of the N-aryl plane to the adjacent imine unit. The structures of 2a and 2b are similar to those of their acetate precursors (1) with a tridentate monoanionic 2-(2′-anilido)-6-imine-pyridine filling three coordination sites of the distorted square planar geometry but differ with a chloride now filling the fourth site. Unlike 1b, the anilido NH proton is not involved in any interor intra-molecular contacts of note.
As a representative of the mono-phenyl pair of structures, a view of the molecular structure of 3a is depicted in Fig. 6; selected bond distances and angles are listed in Table 4 for both 3a and 3b. As with 1 and 2, 2-(2′-anilido)-6-imine-pyridine ligand acts a tridentate ligand with the σ-phenyl ligand now occupying the fourth coordination site to complete a distorted square planar geometry. The phenyl ligand in both structures is tilted with respect to the trans-pyridine unit of the N,N,Nligand and most noticeably for 3a, presumably as a consequence of the variation in steric hindrance imposed by the N-aryl groups , an observation attributable to the strong trans-influence exhibited by the aryl group. In contrast, the exterior nitrogenpalladium distances remain similar in length to those seen in 1 and 2. To accommodate the increased Pd-N(2) pyridine distance, there is increased twisting of the ligand backbone which is most apparent in 3b [tors. N(2)-C(13)-C(14)-C(15) 25.2(4) and N(1)-C(7)-C(9)-N(2) 13.7(4)°]. As with chloride-containing 2, the anilido NH proton shows no notable intra-or inter-molecular contacts of note.
Unfortunately cationic 4 and 5 were not amenable to forming crystals suitable for an X-ray determination. To overcome this practical issue, small amounts of pyridine were added to a solution of 5 in chloroform and hexane slowly diffused forming single crystals of [{2-(C 6 H 4 -2′-NH)-6-(CMev N(4-i-PrC 6 H 4 )C 5 H 3 N}Pd(NC 5 H 5 )][O 3 SCF 3 ] (5′). The molecular structure of the cationic unit 5′ is depicted in Fig. 7; selected bond distances and angles are listed in Table 5. As with a number of the structures reported in this study, two independent molecules (A and B) were present in the unit cell which, in this case, differ most noticeably in the inclination of the N-aryl groups. The structure of 5′ consists of a palladium(II) cationic unit charge balanced by a non-coordinating triflate counteranion. Within the distorted square planar cationic   Bond lengths 1.302 (9) 1.291(4) C(9)-C(7) 1.452 (10) 1.472(4) C(15)-N (3) 1.326 (9) 1.348(4) Bond angles (10) unit, the 2-(2′-anilido)-6-imine-pyridine ligand acts a tridentate ligand and an N-bound pyridine fills the fourth coordination site. Similar to phenyl-bound 3, the monodentate heteroaromatic in 5′ is not co-planar with the trans-pyridine unit of the tridentate ligand. Instead it adopts a tilted configuration [C(13)-N(2)-N(4)-C(27) 58.1(5) A , 60.0(5) B°] which is ca. 8°g reater than that for the aryl group in 3b. Inspection of the trans Pd-N(2) pyridine distance involving the N,N,N-ligand reveals a bond length [Pd(1)-N(2) 1.992(11) A , 1.952(11) B Å] comparable with those seen in 1 and 2, but shorter than that in 3 (vide supra). The NH proton of the anilido unit of the pincer undergoes a modest interaction with a triflate oxygen atom [N(3)⋯O(1) 3.096 A , 3.175 B Å].

Reactivity of 3 towards Selectfluor and XeF 2
In the first instance the reactivity of mono-phenyl containing 3a towards Selectfluor was explored. Typically 3a was treated with excess Selectfluor at 100°C in a toluene-MeCN mixture; these higher temperature conditions having been identified as more conducive to formation of the C-F reductive elimination product. 4c,3c However, biphenyl was the only aryl-containing organic product identified by GC-MS. Likewise using XeF 2 as the oxidant instead of Selectfluor under the same conditions gave only biphenyl.
To investigate the reaction further and potentially observe any possible intermediates, a reaction involving an equimolar ratio of 3a and Selectfluor was undertaken in CD 3 CN at a series of lower temperatures and the reaction monitored by 1 H and 19 F NMR spectroscopy (Scheme 4). After 15 minutes at room temperature the 19 F NMR spectrum revealed full consumption of Selectfluor and a new peak at δ −181 attributable to the formation of hydrogen fluoride. 17 The 1 H NMR spectrum contained signals consistent with biphenyl, the salt [{2-(C 6 H 4 -2-NH)-6-(CMevN(4-i-PrC 6 H 4 )C 5 H 3 N}Pd(NCCD 3 )][BF 4 ] (4) (vide supra) and 1-(chloromethyl)-1,4-diazabicyclo[2.2.2]octan-1-ium tetrafluoroborate, the Selectfluor degradation product. In addition, there were signals present attributable to another palladium species that slowly reduced in intensity over time.
When the reaction was carried out at −40°C, full consumption of Selectfluor was again evident from the 19 F NMR spectrum which also contained a peak attributable to HF, albeit temperature shifted (δ −172). In the 1 H NMR spectrum full conversion of 3a to a single palladium species was observed with the aromatic/pyridyl region integrating to sixteen protons; no peaks assignable to biphenyl nor 4 could be identified. As the reaction mixture was warmed to 0°C, only sharpening of the 1 H NMR spectrum was observed with peaks that clearly match those observed for the decomposing palladium species seen at room temperature ( Fig. S9 in ESI †). In the 19 F NMR spectrum a 1 : 8 ratio between the HF signal (δ −174) and the BF 4 peak (δ −152) accounts for all the fluorine introduced from the Selectfluor (Fig. S10 in ESI †). On warming to room temperature, decomposition of the palladium intermediate ensued generating biphenyl and 4; full conversion being Fig. 7 Molecular structure of cationic unit in 5', including a partial atom numbering scheme. All hydrogen atoms, except for H3, have been omitted for clarity.  (11) observed after 48 hours (Fig. S11 in ESI †). Unfortunately, further attempts to fully characterise the high valent palladium intermediate were unsuccessful. The 1 : 1 reaction of 2,6-diisopropylphenyl-containing 3b with Selectfluor was also explored at a range of different temperatures. However, despite consumption of 3b, there was no evidence for the formation of biphenyl, fluorobenzene nor could any characterisable palladium species be identified. It is unclear as to the origin of these differences in reactivity between 3a and 3b towards Selectfluor.

Conclusions
A new family of imino-based monoanionic N,N,N pincer ligands have been developed that can support neutral palladium(II) acetate (1), chloride (2) and phenyl (3) species; the tetrafluoroborate (4) and triflate (5) salts are also reported. The oxidatively induced Ph-Ph coupling reactions involving 3a described in this work highlights the ability of Selectfluor and xenon difluoride to behave as bystanding oxidants. 3d Using the more sterically bulky 3b, neither biphenyl nor fluorobenzene were produced under similar oxidative conditions. The identity of the palladium intermediate that generates biphenyl and cationic 4 remains uncertain but investigations into the precise nature of this species are ongoing.

General
All operations, unless otherwise stated, were carried out under an inert atmosphere of dry, oxygen-free nitrogen using standard Schlenk and cannular techniques or in a nitrogen purged glove box. Operations involving a Microwave were performed on a CEM Discover Explorer Hybrid instrument. Solvents were distilled under nitrogen from appropriate drying agents 18 or were employed directly from a Solvent Purification System (Innovative Technology, Inc.). The electrospray (ESI) mass spectra were recorded using a micromass Quattra LC mass spectrometer with acetonitrile or methanol as the matrix. FAB mass spectra (including high resolution) were recorded on a Kratos Concept spectrometer with NBA as matrix or on a Waters Xevo QToF mass spectrometer equipped with an atmospheric solids analysis probe (ASAP). The infrared spectra were recorded in the solid state with Universal ATR sampling accessories on a Perkin Elmer Spectrum One FTIR instrument. NMR spectra were recorded on a Bruker DRX400 spectrometer at 400.13 ( 1 H), 376.46 ( 19 F) and 100.61 MHz ( 13 C) or a Bruker Avance III 500 spectrometer at 125 MHz ( 13 C), at ambient temperature unless otherwise stated; chemical shifts ( ppm) are referred to the residual protic solvent peaks and coupling constants are expressed in hertz (Hz). Melting points (mp) were measured on a Gallenkamp melting point apparatus (model MFB-595) in open capillary tubes and were uncorrected. Elemental analyses were performed at the Science Technical Support Unit, London Metropolitan University. The reagents 4-isopropylaniline, 2,6-diisopropylaniline, tin(II) chloride dihydrate, phenyllithium (1.8 M in n-Bu 2 O), silver triflate, silver tetrafluoroborate, 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor™) and 2-bromonitrobenzene were purchased from Aldrich Chemical Co. and used without further purification. The compounds 6-tributylstannyl-2-(2-methyl-1,3-dioxolan-2-yl)pyridine 19 and [(PPh 3 ) 2 PdPh(Br)] 20 were prepared using literature procedures. All other chemicals were obtained commercially and used without further purification.