Chiral Ag( I ) and Pt( II ) complexes of ditopic NHC ligands: synthesis, structural and spectroscopic properties †‡

The butyl and isopropyl derivatives ( 4I , 5Br ) of chiral pool derived bis-imidazolium dehydrohexitol salts have been prepared. The ditopic N-heterocyclic carbenes 4 and 5 form dinuclear Ag( I ) and Pt( II ) complexes. All compounds were fully characterised by multinuclear NMR spectroscopy. The bis-imidazolium salt 4I and platinum complexes cis -[Pt 2 ( μ - 2 )(dmso) 2 Cl 4 ] and cis -[Pt 2 ( μ - 4 )(dmso) 2 Cl 4 ] were characterised by X-ray crystallography. In the case of the Pt( II ) complexes, the carbene ring is positioned in a sterically preferred orientation, approximately perpendicular to the platinum coordination plane. The 1 H, 13 C, 15 N and 195 Pt NMR spectra of the platinum complexes show the presence of rotamers due to hindered rotation about the carbene – metal bond.


Introduction
N-Heterocyclic carbene (NHC) ligands and their transition metal complexes have established themselves as a cornerstone of modern coordination chemistry and are now used in a wide range of applications. Platinum(II)-NHC complexes in particular catalyse a number of important reactions, such as hydrosilylations, 1 hydroaminations, 2 tandem hydroboration-cross-coupling reactions 3 and diboration of unsaturated molecules. 4 Platinum(II)-NHC complexes have also seen recent activity in medicinal applications as possible chemotherapeutic agents. 5 Thus efficient syntheses of platinum-NHC complexes are of considerable current interest. Synthetic routes to Pt-NHC complexes include direct reaction of the carbene precursor in the presence of base, 1e,6 or of the free carbene, with suitable platinum salts. 7 Alternatively, transmetalation of Ag-NHC complexes with a platinum source is also known. 8 Silver (I) carbenes are extensively used as ligand transfer agents for the majority of imidazolium and other azolium salts, forming a part of a convenient, and sometimes the only, route for the synthesis of metal carbene complexes. 9 Ag(I)-NHC complexes have also found many medicinal applications, mainly due to their activity as antimicrobials. 10 Other potential uses include high-end materials applications, such as luminescent chemosensors. 11 Silver-carbene complexes are structurally diverse, displaying a broad range of coordination motifs, ranging from simple two-coordinate linear molecules 9e,12 to helicates, 13 polymers, 14 rings, 15 cages 16 and clusters. 17 Based on our previously reported chiral pool derived dehydrohexitol framework precursor 1, 18 we recently described an efficient method leading to the bis-carbene precursor imidazolium salts 2X (Scheme 1) with 2,5-exo stereochemistry. 19 The endo and exo stereochemistry refers to the substitution with respect to the bent V-shaped core of the fused dehydrohexitol ring. Here we report the synthesis of the isopropyl-and butylimidazole derivatives (4X and 5X) following an alternative synthetic route and expand on the coordination chemistry for this family of bridging NHC ligands, to include examples of their Pt(II) complexes.

Discussion
The 2,5-exo-bisimidazole 3 was prepared from the reaction of ditosylate 1 with imidazole in dmf in the presence of Cs 2 CO 3 (Scheme 1). Subsequent quaternerisation with the corresponding alkyl halide afforded the bis-isopropyl-and butyl-imidazolium salts 4I and 5Br. Following counterion metathesis with potassium hexafluorophosphate in water, 4PF 6 is furnished as a crystalline white solid and 5PF 6 as a colourless viscous ionic liquid. The imidazolium salts have the expected exo stereochemistry at the 2 and 5 positions of the bicyclic ring as in the parent hexitol, L-iditol. The dicationic salts are readily soluble in water and † Dedicated to Professor David Cole-Hamilton on the occasion of his retirement and for his outstanding contribution to transition metal catalysis. ‡ Electronic supplementary information (ESI) available: X-ray crystallographic data as CIF files for the compounds 4I, 8  polar organic solvents such as lower alcohols, acetone, acetonitrile and dmso. Single crystals of 4I suitable for X-ray studies were grown from an acetonitrile solution of the salt, and the structure of the cation is shown in Fig. 1.

Silver(I) complexes
The silver(I) complexes of carbenes 4 and 5 were prepared from the reaction of Ag 2 O with the corresponding imidazolium salts, 4I, 4PF 6 and 5Br. NHC carbenes 4 and 5 form the bridged metallacyclic dinuclear silver complexes, [Ag 2 (μ-NHC) 2 ][X] 2 shown in Scheme 1, irrespective of the metal to ligand ratio and type of counterion used. The analogous methyl-imidazolyl complex [Ag 2 (μ-2) 2 ][PF 6 ] 2 and its solid-state structure has been reported previously by us. 19 Unfortunately, the isopropyl and butyl derivatives, 6I and 7Br, did not afford good crystals of sufficient quality to allow for their X-ray structure determinations. As was the case for NHC ligand 2, the neutral acyclic bis-monocarbene complexes (11) were not observed. Electrospray mass spectra show maximal mass peaks at m/z 1001 and 1009 for the silver metallacycle complexes, 6I and 7Br respectively, corresponding to loss of one of the counterions from the parent compound, [Ag(μ-NHC)] 2 [X] 2 . In the 13 C NMR spectra of the silver complexes the carbene resonance appears as a sharp  singlet at δ 180.6 ppm for 6I and δ 181.6 ppm for 7Br. Coupling to 107 Ag or 109 Ag was unobserved in both cases. Silver-carbene complexes have been used previously in transmetalation reactions with platinum(II) salts to afford the corresponding Pt(NHC) complexes. 8b, 20 In the case of the silver complex 7Br reaction with Pt(cod)Cl 2 afforded mixtures of Pt(II)-containing species and partially protonated carbene ligand.

Platinum(II) complexes
In order to avoid time-and resource-consuming routes, the platinum complexes 8-10 were prepared directly from the reaction of the corresponding ligand salts (2PF 6 , 4PF 6 and 5PF 6 ) with PtCl 2 or K 2 PtCl 4 in quantitative yields (Scheme 1). Reactions were carried out in the presence of NaOAc in dmso, under aerobic conditions using unpurified technical grade solvent. Reactions in other solvents, e.g. dma (N,N′-dimethylacetamide), afforded complex mixtures of intractable products. The above synthetic procedure afforded the bis-monocarbene complexes, cis-[Pt 2 (μ-NHC)(dmso) 2 Cl 4 ], regardless of the metal to ligand ratio used. 7,8,20 1 : 1 metal to ligand reactions afforded the corresponding cis-[Pt 2 (μ-NHC)(dmso) 2 Cl 4 ] complexes, with the excess imidazolium salt remaining unreacted. Complexes 8-10 are air-and moisture-stable and can be stored for prolonged times in air without any visible decomposition. They are soluble in chlorinated solvents, acetonitrile and dmso.

Solution NMR measurements
Relatively small changes are observed in the 1 H NMR spectra for the hydrogen atoms of the proligands of 2, 4 and 5 upon coordination to silver (I). More pronounced deshielding of the proton resonances, however, is seen for the platinum complexes, most likely due to the divalent metal. Notably, there are large downfield shifts of the methine protons (H 2/5 ) adjacent to the imidazolyl nitrogen atoms from ca. δ 5.1 ppm (CD 3 CN) in the imidazolium salts to δ 5.9-6.1 ppm (CD 3 CN) in the coordinated ligands. A large downfield shift is also observed for the isopropyl methine proton of 9, from δ 4.73 ppm in 4I to 5.63 ppm (CD 3 CN).

Restricted rotation about the C-Pt bond
The 1 H and 13 C NMR spectra of the platinum complexes, 8-10, reveal more than one isomers present in solution which have been attributed to rotamers arising from restricted rotation about the Pt-C NHC bond. High metal-carbene rotation barriers (>92 kJ mol −1 ) have been observed for Rh(I)-and Ir(I)-NHC systems and attributed mainly to steric effects. 21 Similarly, for Pt(NHC) (dmso)Cl 2 -type complexes Rourke et al. have reported barriers to rotation in excess of 85 kJ mol −1 . 8a In the case of the dinuclear complexes, 8-10, there are three possible rotamers arising from slow rotation about the Pt-C NHC bond; two of C 2 symmetry with the dmso ligands either in (isomer A, Scheme 1) or out (isomer B) with respect to the dehydrohexitol core, and one of C 1 symmetry with in and out dmso ligands (isomer C). All three rotamers of 8-10 were observed in different ratios, although due to the complexity of the overlapping signals, these rotamers could not be individually assigned. One common feature in the spectra of the complexes, supporting the existence of three isomers in solution, is the appearance of four distinct doublets for one of the imidazolyl proton resonances, with one doublet for each of the C 2 symmetric isomers and two doublets for the C 1 symmetric isomer. In addition, the two methyl groups of the coordinated dmso are diastereotopically inequivalent, as of course are the methyls on the isopropyl group of 9. In an attempt to simplify the 1 H NMR spectra, a dmso-d 6 solution of complex 8 was heated to 100°C. However, no significant changes in the chemical shifts were observed, leading us to conclude that a high barrier to rotation about the Pt-C NHC bond also exists for these complexes.
In the 195 Pt NMR spectra of complexes 8-10 two signals were observed in each case, centred at ca. −3500 ppm (referenced to Na 2 PtCl 6 ). 22 Presumably, some of the rotamer signals remain unresolved in the corresponding 195 Pt NMR spectra. For comparison, the δ 195Pt reported for the related carbene complexes, [Pt(NHC)(dmso)Me 2 ], are in the region of −3900 to −4000 ppm. 20 The effect of the different N-imidazole substituents (Me, iPr, Bu) of complexes 8-10 on the 195 Pt NMR chemical shifts (δ 195Pt ) is negligible. This is in agreement with reports for other PtCl 2 systems, such as those of chelating dipyridyl ligands. 23 Due to solubility limitations, different solvents were used for each complex during these measurements (dmso-d 6 for 8, CD 3 CN for 9 and CD 2 Cl 2 for 10). Contrary to previous observations, where large Δδ 195Pt of ca. 400 ppm were observed with changes in the solvent from CD 2 Cl 2 to dmso-d 6 , there were no significant solvent effects observed for complexes 8-10. 24 1 H-15 N HMBC spectra were also collected for the platinum complexes. In most cases analyses of the cross-peaks in the twodimensional spectra provided a means of differentiating and assigning the two non-symmetrically substituted imidazolyl 15 N resonances. Relatively small differences in the chemical shifts of the imidazole derived nitrogens were observed (Δδ 15N ), with the largest Δδ 15N observed for complex 9 at 16 ppm and the smallest for complex 10. In this case, the two 15 N resonances centred at 204.5 ppm remained unresolved. Although the signals for N O and N R in the 15 N dimension of the spectra for 8-10 were not resolved further, the presence of rotamers is implied after inspection of the cross-section of the peaks in the 2D-spectra (where N O represents the nitrogen atom next to the oxolane ring and N R the one next to the corresponding alkyl substituent).
Solid state structures of the Pt(II) complexes. The solid-state structures of platinum complexes 8 and 9 were determined by synchrotron X-ray crystallography. Complexes 8 and 9 adopt the same C 2 symmetric spatial arrangement shown in Fig. 2, with complex 9 containing a true C 2 crystallographic axis. The two platinum centres are trans to each other, facing away from the dehydrohexitol core and the dmso ligands assume a syn arrangement facing towards the core (isomer A, vide supra). This more crowded conformation may be stabilised by non-classical C-H⋯O hydrogen bonding interactions between the dmso oxygen and bridgehead hydrogen atoms of the dioxolane unit; for complex 9 the relevant O⋯H distances are 2.54 and 2.46 Å, and for 8, 2.47 Å (two distances equal by symmetry). 25 The Pt-C NHC bonds are in the range 1.88(2)-1.98(2) Å, at the lower end of the range reported for other Pt-NHC-dmso complexes. 7,8 The carbene ring is placed in a sterically preferred orientation, approximately perpendicular to the platinum coordination plane in each case; the corresponding dihedral angles between the imidazole and coordination planes are 81.9°for 8, and 86.2°and 89.7°for 9.

Experimental General remarks
All manipulations were performed using standard glassware under aerobic conditions, except where otherwise noted. Solvents of analytical grade and deuterated solvents for NMR measurements were used as received. Literature methods were employed for the synthesis of 1 19 and Ag 2 O. 26 All other reagents were used as received. Ether means diethyl ether and dmf dimethylformamide unless specified otherwise. NMR spectra were obtained on Bruker Avance AMX 250, 400, 500, 600 (QCI Quadruple Resonance CryoProbe) or Jeol Eclipse 300 spectrometers. The chemical shifts are given as dimensionless δ values and are frequency referenced relative to TMS for 1 H and 13 C and Na 2 PtCl 6 for 195 Pt. For 1 H-15 N heteronuclear multiple-bond correlation (HMBC) experiments, CH 3 NO 2 was used as the standard for the 15 N chemical shifts (δ = 381.7 vs. liquid NH 3 ). 27 In the HMBC experimental, N R stands for the alkyl substituted nitrogen of the imidazole ring and N O for the one next to the dioxolane ring.
Coupling constants J are given in hertz (Hz) as positive values regardless of their real individual signs. The multiplicity of the signals is indicated as s, d, or m for singlets, doublets, or multiplets, respectively. The abbreviation br is given for broadened signals. Mass spectra and high-resolution mass spectra were obtained in electrospray (ES) mode unless otherwise reported, on a Waters Q-Tof micromass spectrometer. IR spectra were measured on a JASCO 660plus FT-IR spectrometer from 4000 to 600 cm −1 .
Preparation of cis-[Pt 2 (μ-2)(dmso) 2 Cl 4 ], 8. 2PF 6 (0.187 g, 0.33 mmol), K 2 PtCl 4 (0.278 g, 0.67 mmol) and NaOAc (0.057 g, 0.70 mmol) were dissolved in 1 mL of dmso at 70°C. The reaction mixture was stirred at that temperature for 3 days. The solution was dried under vacuum and the yellowish solid obtained was washed three times with methanol and subsequently dried. The white solid obtained was recrystallised by diffusion of hexane into a dichloromethane solution to afford block colourless plates of the product. Yield: 0.300 g (94%). 1

X-ray crystallography
Data for 4I were measured at 120 K on a Bruker Nonius KappaCCD diffractometer at the window of a Bruker Nonius FR591 rotating anode (λ Mo-Kα = 0.71073 Å) driven by COLLECT and processed by DENZO software. 28 The structure was determined in SHELXS-97 and refined using SHELXL-97. 29 Data for 8 and 9 were obtained from very small and weakly diffracting crystals by use of synchrotron radiation (λ = 0.6889 Å) at 120 K, with a Crystal Logics kappa diffractometer and Rigaku Saturn 724+ CCD detector at beamline I19 of Diamond Light Source; software was Rigaku CrystalClear, 30 and Bruker APEX2 31 and SHELXTL. 29 Key crystallographic data are shown in Table 1.
In addition to the intended compound 9 (with 8 identical molecules in the tetragonal unit cell, all of the same chirality), the structure also contains highly disordered solvent and/or other components that could not be modelled as discrete atoms and could not be identified from the observed electron density distribution. This has been treated with the SQUEEZE option of the program PLATON. 32 The refined structural model contains only the ordered part of the crystal structure and the unidentified disordered components are not included in any of the tabulated or deposited values. The crystal structure of 8 contains disordered dichloromethane solvent molecules, which it was possible to model with discrete atom positions. For all three structures, the correct enantiomer was confirmed on the basis of significant anomalous scattering effects. 33 Crystallographic data for all compounds have been deposited with the Cambridge Crystallographic Data Centre as supplementary publications CCDC 893546-893548.

Conclusions
Short synthetic routes to the chiral, ether-functionalized NHC precursors, 2OTs, 4I and 5Br have been developed. The bridging ligands 2, 4 and 5 form either cationic dinuclear cyclic structures with Ag(I) or neutral linear complexes in the case of Pt(II). The robust nature of the Pt(II) complexes is indicated by their synthesis being achieved under aerobic conditions using bench grade solvents. For the cis-Pt(dmso)Cl 2 complexes, hindered rotation of the carbene ligand about the metal-NHC bond is evident in their 1 H, 13 C, 15 N and 195 Pt NMR spectra, where more than one rotamers can be observed.