Article Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
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Controlling Ligand Exchange through Macrocyclization Veronica Carta, S. Hessam M. Mehr, and Mark J. MacLachlan* Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada S Supporting Information *
ABSTRACT: Ligand exchange at a sterically hindered palladium center was investigated for six different ligands. The palladium atom was coordinated to a tridentate, NNN pincer bis(amido)pyridine macrocycle to produce a square-planar complex, in which an acetonitrile molecule occupies one of the coordination sites. Kinetic studies showed that ligand exchange at the palladium center proceeds through an associative mechanism and, as a consequence, is impeded by the small size of the metallomacrocycle cavity. The ligand-exchange rate on the palladium center between acetonitrile and six different ligands has been investigated and compared to the exchange rate on the corresponding open form. Our results demonstrate that macrocyclization of ligands is a way to modify the rate of guest exchange in a square-planar metal complex.
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INTRODUCTION Pincer ligands are a class of chelating compounds that bind strongly to a metal through three coordination sites.1−6 The tridentate ligand confers high stability to the complex but still leaves a vacant coordination site, which is usually occupied by a solvent molecule. Pincer complexes have attracted enormous attention for catalysis, sensing, and other applications.7−10 Tridentate planar bis(amido)pyridine ligands are pincer ligands that have been widely exploited in supramolecular chemistry.11−14 Their ability to coordinate to metals like palladium(II) and platinum(II) with square-planar geometry and the potential to modify their structures make them suitable for forming catenanes,15,16 rotaxanes,15,17 and molecular machines.18,19 Ligand exchange on the fourth coordination site of the metal center is also important for several other applications such as designing receptor systems, catalysts20 and drugs. It has been previously reported that bis(amido)pyridine ligands with bulky side groups can be employed to control ligand exchange on the fourth coordination site of palladium. For instance, the incorporation of larger aromatic rings on the pincer backbone results in a NNN pincer complex of Pd2+ that has enhanced binding between 2-chloroethyl ethyl sulfide and the palladium.21 Bulky pincer ligands have been shown to affect the reactivity of transition-metal pincer complexes,22 and ligand exchange on the fourth coordination site of the palladium becomes slower with an increase of the steric hindrance near the metal center.23 This is related to the ligand-exchange mechanism on the palladium center, which is usually associative and is therefore impeded by steric bulk around the metal center. In catalysis, this concept has been used to convert palladium(II) complexes from olefin oligomerization catalysts to polymerization catalysts.24 Coordination of bulky α-diimine ligands to a palladium (or nickel) catalyst inhibits associative © XXXX American Chemical Society
displacement of the unsaturated polymer chain, preventing chain transfer and favoring olefin insertion.25,26 Here we investigate control of ligand exchange on a palladium pincer complex by using a supramolecular approach. A tridentate macrocyclic ligand with a NNN pincer bis(amido)pyridine functionality has been prepared (Figure 1a). The
Figure 1. (a) NNN pincer metallomacrocycle of Pd2+. An acetonitrile molecule occupies the fourth palladium coordination site. (b) NNN pincer complex of Pd2+. This complex represents the open form of the metallomacrocycle.
macrocycle coordinates to a palladium ion to give a rigid pincer complex with a small cavity; an acetonitrile molecule occupies the palladium atom’s fourth coordination site. The small size of the cavity provides steric hindrance and impedes the ligand exchange between acetonitrile and other bulky ligands. Ligandexchange studies were performed with several ligands, and the rate of exchange on the new metallomacrocycle was compared with the rate of exchange for its corresponding open form (Figure 1b). Received: January 5, 2018
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DOI: 10.1021/acs.inorgchem.8b00031 Inorg. Chem. XXXX, XXX, XXX−XXX
Article
Inorganic Chemistry Scheme 1. Synthesis of Metallomacrocycle 3
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RESULTS AND DISCUSSION Metallomacrocycle 3: Synthesis and Behavior in Solution. The NNN pincer bis(amido)pyridine macrocycle 2 was prepared by the route shown in Scheme 1. The ring-closing (final) step proceeded in 71% yield in high dilution conditions (2.5 mM). Notably, the macrocycle has C2v symmetry by 1H NMR spectroscopy, and the components of the macrocycle are fluxional. A crystal structure of compound 2 (Figure 2) also
past the acetonitrile molecule coordinated to the metal center, and the conformation is blocked on one side with respect to the palladium−acetonitrile bond. A 1H−1H COSY NMR experiment was used to correctly assign the chemical shift of each hydrogen atom in complex 3 (Figure S5). A single crystal of 3 suitable for single-crystal X-ray diffraction (SCXRD) was obtained from slow evaporation of a solution of 3 in 1:1 acetonitrile/dichloromethane (DCM). The crystal structure (Figure 3) confirms that the palladium ion
Figure 2. Solid-state structure of compound 2 as determined by SCXRD: (a) front view; (b) side view.
shows that the macrocycle appears flexible despite the bridge between the aryl groups. Metalation of macrocycle 2 with Pd(OAc)2 at 50 °C afforded a yellow metallomacrocycle 3 in 54% yield. The new compounds were characterized by 1H and 13 C NMR spectroscopy and high-resolution electrospray ionization mass spectrometry (HRESI-MS). The 1H NMR signals (in CDCl3) corresponding to the amidic hydrogen atom (7.62 ppm) disappeared upon coordination to palladium(II) and a new peak corresponding to the coordinated acetonitrile appeared at 1.50 ppm (excess free acetonitrile is observed at 2.02 ppm). Notably, the methylene hydrogen atoms present in macrocycle 2 became diastereotopic upon Pd2+ coordination, indicating reduction of the C2v symmetry. This shows that, on the time scale of the NMR experiment, the ring in compound 3 is unable to skip
Figure 3. Solid-state structure of compound 3 as determined by SCXRD: (a) front view; (b) side view; (c) top view.
has square-planar geometry where it is coordinated to the pyridine, two amidic nitrogen atoms, and acetonitrile. The metallomacrocycle’s cavity is smallthe distance between the two aromatic rings is 5.80 Åbut the system is not particularly strained because substituents are oriented out of the plane of the pyridine and metal to accommodate the acetonitrile guest (Figure 3b). This geometry is consistent with the solution 1H NMR data, which showed that the methylene protons are diastereotopic (Figure S3). B
DOI: 10.1021/acs.inorgchem.8b00031 Inorg. Chem. XXXX, XXX, XXX−XXX
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Inorganic Chemistry
noticeable that the structure has substantial disorder located in two of the bridging chains and on some phenyl rings. Restraints on the bond lengths and angles worked well enough to model the phenyl rings, while for the bridging chains, it was necessary to split the electron density into two parts and fix the total occupancy to 1. Despite the complexity of the structure and the weak diffraction of the crystal, Rint was brought down to 15.3%. The structure is reliable enough to conclude that the aggregate formed is a tetrameric macrocycle of macrocycles. Model Compound for Ligand Exchange. In order to explore the exchange of ligands at palladium in metallomacrocycle 3, we first prepared a model complex, 5, as shown in Scheme 2. In this complex, the phenyl rings are not tethered together, and they are instead free to move far apart from each other. Compound 5 was characterized by 1H and 13C NMR spectroscopy, HRESI-MS, elemental analysis, and SCXRD. Comparing the 1H NMR data with compound 3 shows that for compound 5 the methylene protons are not diastereotopic. These data are consistent with the average C2v symmetry in solution. The 1H NMR spectrum of compound 5 in CD2Cl2 (Figure S13) also shows some broad peaks that are not present if the spectrum is collected in a coordinating solvent such as dimethyl sulfoxide (DMSO). In DMSO (Figure S12), the peak corresponding to coordinated acetonitrile (1.80 ppm in CD2Cl2) is not present either. This suggests that DMSO exchanges with acetonitrile, shifting the equilibrium toward a monomeric complex, while in chloroform, some oligomer is formed. As with compound 3, heating compound 5 in chloroform for 48 h at reflux produces a new species 5*, which is likely to be some higher-order aggregate of compound 5, where the acetonitrile molecule is not coordinating, similar to the cyclic tetramer 3*. (Unlike in the case of 3*, we have not been able to isolate and purify 5*, but it behaves similarly to 3*, leading us to postulate that it is also an aggregate.) A single crystal of 5 was produced from vapor diffusion of pentane into a solution of 5 in 1:1 chloroform/acetonitrile. The SCXRD structure of compound 5 is shown in Figure 5. The
It has been previously reported that some palladium bis(amido)pyridine complexes are present in an equilibrium between a monomeric form and a cyclic hexameric or tetrameric form.27−29 This equilibrium is facilitated by the lability of the acetonitrile molecule coordinated to the palladium, which in solution exchanges with another bis(amido)pyridine complex that coordinates through its oxygen atom to form a cyclic structure. The addition of ligands that bind the metal center can strongly disrupt this equilibrium, shifting it toward the monomeric form. We anticipated that the macrocyclic structure of 3 would inhibit aggregation and thereby stabilize the monomeric form of the compound. However, through a variable-temperature (VT) 1H NMR spectroscopy experiment (Figure S8), we found that when metallomacrocycle 3 is heated in chloroform, it partially converts into a new compound (3*). The species 3* is stable and does not revert to the monomeric form upon cooling of the sample to room temperature. 1H NMR spectroscopy indicates that the new product is structurally similar to the monomer but does not contain acetonitrile. In addition, the peaks corresponding to the pyridine protons become asymmetric (Figure S6). Our data suggest that compound 3 ejects acetonitrile to form oligomer 3*. A single crystal of compound 3* was grown by vapor diffusion of cyclohexane into a solution of 3* in dichloroethane. Figure 4a shows the crystal structure of this aggregate; it is a
Figure 4. (a) Solid-state molecular structure of compound 3* as determined by SCXRD. Compound 3* is a macrocycle of macrocycles, where each monomer is bridged by a carbonyl group to the next palladium atom, forming a cyclic tetramer. (b) Space-filling model (based on van der Waals radii) for compound 3*. The color of the atoms indicates the atomic displacement parameters: blue if they are small, and red if they are high.
cyclic tetramer where each monomer is bridged to the next palladium atom through a carbonyl group. As shown in the space-filling model in Figure 4b, the cavity inside compound 3* is quite small, with the Pd1−Pd3 distance being 7.878(4) Å and the Pd2−Pd4 distance being 7.095(3) Å. Figure 4b also shows the atomic displacement parameters for compound 3*. It is
Figure 5. Solid-state molecular structure of compound 5 as determined by SCXRD: (a) front view; (b) side view.
Scheme 2. Synthesis of the Open Complex 5
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DOI: 10.1021/acs.inorgchem.8b00031 Inorg. Chem. XXXX, XXX, XXX−XXX
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Inorganic Chemistry
their applicability as catalysts in the Suzuki−Miyaura crosscoupling reaction. For pyridine, DMAP, and triphenylphosphine, the bridging chain on compound 3 does not provide enough steric bulk to significantly slow the exchange process. In spite of this, NMR studies show that the bridging chain provides enough steric hindrance to affect the rotation of pyridine and DMAP around the N−Pd bond. Specifically, Ho1 and Hm1 (Figure 8a)
phenyl groups are both on one side with respect to the palladium coordination plane, but they are able to skip past the acetonitrile molecule in solution, as supported by the 1H NMR data (Figure S13). This is consistent with the crystal structure recently obtained for compound 5 by Jerome et al., which presents the same unit cell. Ligand Exchange Studies: Triphenylphosphine, Pyridine, and (Dimethylamino)pyridine (DMAP). The ligands selected to investigate the exchange with acetonitrile on the palladium atom are shown in Figure 6. Triphenylphosphine,
Figure 6. Compounds used to investigate ligand exchange: pyridine, triphenylphosphine, DMAP, quinoline, acridine, and 2,6-lutidine.
pyridine, and DMAP exchange quickly with acetonitrile both in the metallomacrocycle 3 and in the open complex 5. Following ligand exchange by 1H NMR spectroscopy, the disappearance of peaks corresponding to higher-order aggregates (3* and 5*) is notable. The equilibrium shifts toward the monomeric form as ligand exchange completes. The metallomacrocycle exchange products were characterized by 1H and 13C NMR, ESI-MS, elemental analysis, and SCXRD. Molecular structures of compounds 5-pyr and 5-PPh3 determined by SCXRD are shown in Figure 7. Attempts to grow single crystals of compound 5-dmap suitable for SCXRD were unsuccessful. From the crystal structures of compounds 5-pyr and 5-PPh3, it is clear that the two phenyl rings of the pincer ligands do not move very far from each other upon coordination of pyridine or triphenylphosphine. We anticipated that these ligands, which are substantially bulkier than acetonitrile, would lead to a large splaying of the phenyl rings. In fact, 5-pyr has nearly perfect square-planar geometry at the Pd 2+ center, and the triphenylphosphine complex 5-PPh3 shows only a small distortion from square planar (the torsion angle between the the NNN-Pd plane and the phosphorus atom is 15.78°). This is in agreement with the crystal structure published by Jerome et al. for compound 5-PPh3, which presents the same torsion angle and crystallizes in the same unit cell.30 Jerome et al. synthesized compounds 5 and 5-PPh3 and similar palladium complexes with substituents in the ortho positions and studied
Figure 8. (a) Structure of DMAP and pyridine, indicating the protons on the pyridyl ring. (b) High-temperature 1H NMR studies for compound 3-dmap. (c) High-temperature 1H NMR studies for compound 3-pyr. Residual C2HDCl4 in C2D2Cl4 is identified with the asterisk. The peaks corresponding to the ortho and meta positions become sharper as the temperature increases, generating two distinct signals. The signals in blue correspond to the ortho protons, whereas the red peaks are generated by the protons in the meta position.
experience large differences in chemical shift as a result of the ring current from Ho2 and Hm2, which, combined with the intermediate rate of ligand rotation at room temperature, makes them completely invisible in the room temperature 1H NMR spectra of compounds 3-pyr and 3-dmap. That said, the ortho and meta resonances can be detected at 113 °C, where the rotation of pyridine and DMAP is fast enough for the resonances to become equivalent (Figure 8). High-temperature
Figure 7. Solid-state molecular structures of (a) compound 5-pyr and (b and c) compound 5-PPh3 as determined by SCXRD. D
DOI: 10.1021/acs.inorgchem.8b00031 Inorg. Chem. XXXX, XXX, XXX−XXX
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H−1H COSY and NOESY NMR experiments confirmed the correct assignment of the spectra (Figures S33, S39, and S40). At low temperature, on the other hand, ligand rotation slows to the point where four distinct 1H resonances emerge (Figure 9).
Table 1. Free Energies of Activation for Ligand Rotation, ΔGrot⧧, in kJ/mol and kcal/mol, for 3-pyr and 3-dmap, Obtained from Ab Initio Techniques and VT NMR Data,a Using Either the Eyring Equation or the Coalescence Temperature computational calculationsb
from Tc
ΔGrot⧧
3-pyr
3-pyr
kJ/mol kcal/mol
46.5 11.1
52 12
from the Eyring plot
3-dmap 3-pyr 48 12
54 13
3-dmap 50 12
a
The rotation rate constants at different temperatures (used to obtain the ΔGrot⧧) were calculated using approximations of the Bloch equation. The uncertainties associated with these values are estimated to be about ±10−15%.31 bThe B3LYP hybrid functional was used in conjunction with the 6-31+G(d,p) basis set. The LANL2DZ basis set and LANL2 core potential were used in the case of platinum. All calculations were carried out using the Gaussian 09 (revision D.01)33 suite of ab initio codes. The solvent and dispersion effects are ignored.
Experimental values of ΔGrot⧧ were calculated using two different methods: by the Eyring plot or through determination of the coalescence temperature, Tc.31,32 ΔGrot⧧ can also be calculated by ab initio methods, obtaining the initial coordinates from the crystal structure of 3-quin, which was modified by changing the quinoline ligand to pyridine, with the assumption that doing so does not significantly perturb the overall geometry of the molecule. More details regarding the computational and experimental determinations of ΔGrot⧧ can be found in the Supporting Information. Ligand-Exchange Studies: Quinoline, Acridine, and 2,6-Lutidine. We next investigated bulkier ligands (quinoline, acridine and 2,6-lutidine), which we expected to show marked differences in the exchange rate between the open complex and strapped metallomacrocycle. When quinoline was added to the open complex compound 5, the coordinated acetonitrile was rapidly exchanged for quinoline, similar to the behavior observed with pyridine. When quinoline was added to compound 3, however, exchange was much slower and completed in 55 min. The crystal structure of compound 3quin shows that quinoline coordinates with the phenyl group pointing away from the cavity in order to reduce any steric strain (Figure 10). Using the atomic coordinates obtained from the SCXRD data for 3-quin, we calculated the size of the complex cavity with the software POVME2.34 This calculation indicates that the cavity is quite small (26.5 Å3) compared with the volumes of quinoline, acridine, and 2,6-lutidine reported in the literature: 123, 166, and 113 Å3, respectively.35,36 Acridine and 2,6-lutidine exchange slowly with the acetonitrile in both compounds 3 and 5. It is possible to follow the exchange process by 1H NMR spectroscopy. Figure 11 shows the kinetic studies performed on compound 5 during the exchange of acetonitrile with acridine and 2,6-lutidine. Ligand exchange with acridine reaches completion after 28 min, while ligand exchange with the more sterically hindered 2,6lutidine is complete after 40 min under the same conditions. This difference is probably due to the presence of the two methyl groups on lutidine. Ligand exchange obeys a secondorder kinetic rate law characteristic of an associative reaction mechanism, where both acetonitrile and the new ligand take part in the transition state. The solid-state molecular structures of the exchanged products of compound 5 are shown in Figure 12. For these complexes, the metal center is nearly perfectly square-planar
Figure 9. (a) Structure of pyridine and DMAP, indicating the protons on the pyridyl ring. (b) Low-temperature 1H NMR studies for compound 3-dmap. (c) Low-temperature 1H NMR studies for compound 3-pyr. Residual CHDCl2 in CD2Cl2 is indicated with the asterisk. The peaks corresponding to the ortho and meta positions become sharper as the temperature decreases, generating four distinct signals. The signals in orange correspond to the hydrogen atoms pointing inside the cavity, which are significantly shielded by the macrocycle’s phenyl groups, whereas the green peaks are the hydrogen atoms pointing away from the cavity.
The chemical shift difference is especially dramatic between Ho1 and Ho2 (3.30 ppm for 3-dmap and 3.55 ppm for 3-pyr), given Ho1’s position in the diamagnetic ring current. Low-temperature 1H−1H COSY and HSQC NMR experiments confirmed the assignment of these protons (Figures S35, S42, and S43). The free energies of activation for ligand rotation, ΔGrot⧧, for compounds 3-pyr and 3-dmap are reported in Table 1. E
DOI: 10.1021/acs.inorgchem.8b00031 Inorg. Chem. XXXX, XXX, XXX−XXX
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Figure 10. Solid-state structure of compound 3-quin as determined by SCXRD: (a) front view; (b) side view; (c) top view.
8 h, after which it reached 70% completion. On the other hand, the exchange between acetonitrile and 2,6-lutidine on compound 3 was monitored for 10 h, after which the reaction was only 50% complete. Assuming that second-order kinetics holds, extrapolation from a linear fit shows that the time to reach 90% conversion would be 23 and 80 h for acridine and 2,6-lutidine, respectively. The exchange process is significantly slower for 2,6-lutidine than for the other two ligands, an effect attributed to the steric bulk given by the methyl groups. From the crystal structure of 3-acr (Figure 14), it is possible to see that the phenyl moieties bend to an almost 90° angle in order to accommodate the acridine molecule. Different from 5acr, the acridine molecule does not stack with the phenyl moieties of the pincer ligand. Instead, in the crystal packing, two acridine molecules interact through π−π stacking (distance between phenyl rings: 3.6 Å), forming dimers (Figure 15). Therefore, our results clearly show that the ligand exchanges on compounds 3 and 5 are dramatically different; the rate of ligand exchange on 5 was 50−120 times faster than that on 3. Even though the tethering group is far from the metal center, forming the metallomacrocycle substantially affects the sterics near the metal center and thus affects the kinetics of ligand exchange. This can be explained by the formation of a transition state where both the acetonitrile, which is leaving, and the new ligand, which is coordinating, are participating. We think that the small cavity in compound 3 allows the formation of a five-coordinate transition state. This is because the cavity does not surround the ligands in the plane of the pincer ligand but bends away to accommodate bulky guests at the metal center. This can be noted in the crystal structures of 3, 3-quin, and 3-acr, where the ligands do not sit inside the cavity, and the phenyl groups bend up to almost a 90° angle. The kinetic studies show that the reaction follows a second-order rate law, in agreement with an associative mechanism with two separate molecules participating in the transition state. The small size of the cavity, estimated to be 26.5 Å3, provides steric hindrance, which slows ligand exchange on the palladium.
Figure 11. Ligand-exchange kinetic study on compound 5, performed with acridine (blue circles) and 2,6-lutidine (orange triangles). 1/X corresponds to the inverse of the concentration of compound 5. The initial concentrations of both 5 and the additional ligand were 0.013 M.
and the phenyl rings are not significantly splayed apart. This possibly indicates that the open complex can easily accommodate the new ligands even if the kinetic studies reveal that this exchange is slow. In all of the complexes shown in Figure 12, the pincer ligand’s phenyl rings point toward opposite sides of the palladium−pyridine plane. For compound 5-acr, the distance between the aryl rings of the pincer ligand and coordinated acridine is 3.6 Å, indicating a weak intermolecular interaction. In compound 5-lut, the distance between the methyl hydrogen atoms of 2,6-lutidine and the pincer ligand’s aromatic rings is 3.0 Å, suggesting a CH−π interaction. Regarding 5-quin, one of the pincer ligand’s phenyl moieties stacks with one aromatic ring (the distance between them is 3.7 Å), while there is no stacking for the other phenyl moiety. Figure 13 shows the kinetic study of ligand exchange in metallomacrocycle 3 with quinoline, acridine, and 2,6-lutidine. The 1H NMR data fit to a second-order kinetic rate law for compound 3, at least for conversion of
