Bisphosphine based hetero-capsules for the encapsulation of transition metals

Abstract

Just mixing of solutions of tetracationic diphosphine ligands and tetraanionic calix[4]arene building blocks leads to the formation of supramolecular heterocapsules that coordinate a palladium metal within the cavity of the assembly, giving rise to a new class of potential supramolecular transition metal catalysts.

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Supramolecular capsules present an important class of architectures that can reversibly accommodate smaller molecules in their cavities.¹ These capsules consist of two or more building blocks that have a similar size, complementary functional groups and associate via multiple non-covalent interactions such as hydrogen bonds, metal–ligand and ionic interactions. A wide variety of homo- and heterocapsules based on functionalized calixarenes, resorcinarenes and other building blocks have been reported.² The encapsulation properties of these hosts enable their utilization as nanosized reactor vessels and so far their use has been explored for the stabilization of reactive intermediates, for organic transformations and for catalysis.³

Many reactions of interest require well-defined transition metal complexes as catalyst, and the activity and selectivity of these catalysts is determined to a great extent by the ligand associated with the metal. So far only a few supramolecular complexes have been reported in which the catalytic potential of an encapsulated transition metal has been explored. Raymond and Bergman et al. have encapsulated iridium-complexes in supramolecular coordination assemblies, which resulted in substrate selectivity (on the basis of size and shape) in the C–H bond activation of aldehydes.⁴ We have introduced a templated approach for the encapsulation of ligands and their metal-complexes,⁵ in which template-ligands have a bifunctional character in that they coordinate to the active metal center and function as a template for the capsule formation. Such encapsulated rhodium complexes were shown to have unusual reactivity and selectivity in the hydroformylation of 1-octene.

Diphosphine based metal complexes represent an important class of catalysts and we anticipated that hetero-capsules based on functionalized diphosphine ligands and well-known building blocks such as calix[4]arene would provide a new class of easily accessible supramolecular complexes. In this strategy a well-defined transition metal complex is an integrated part of the capsule with the transition metal located inside the capsule, and more importantly, the metal is not involved in the assembly process and is therefore available for the catalytic process. Since the crucial building block, i.e. the diphosphine ligand, contains a donor-atom site for metal complexation as well as functional groups for capsule formation, the present strategy comprises a templated approach to metal encapsulation.^5a In this communication we report the formation and characterization of capsules 1·2 that consist of a tetracationic diphosphine ligand 1a or a palladium complex thereof (1b or 1c) and a tetraanionic calix[4]arene 2 (Fig. 1).

Fig. 1 Molecular structures of 1a, 1b, 1c, and 2 and the structure of capsule 1a·2 obtained by molecular modeling.‡

Diphosphine ligands with a rigid backbone such as the xantphos-type ligands, generally have a concave structure defined by the backbone and the four phenyl-groups. We realized that simple functionalization of these four phenyl-groups would provide a building block that would be of similar size to a functionalized calix[4]arene and should form a supramolecular capsule if the interactions are complementary. Tetrasulfonatocalix[4]arene 2 has already been reported by Timmerman and Crego-Calama et al. and forms supramolecular capsules with tetracationic functionalized calix[4]arenes and porphyrins.⁶ Protonation of previously reported 4,5-bis[bis(p-((diethylamino)methyl)phenyl)phosphino]-9,9-dimethylxanthene 1 by HCl yields a tetraammonium substituted xantphos-type ligand 1a (Fig. 1).^7a Molecular modeling shows that ligand 1a and calix[4]arene 2 are similar in size and complementary in function and should form capsule 1a·2via multiple ionic interactions (Fig. 1).

Mixing equimolar solutions of 1a and 2 in water resulted in the precipitation of capsule 1a·2 as a white solid, which was isolated by filtration and appeared to be soluble in methanol and dmso.§ The ¹H NMR spectra of 1a·2 in CD₃OD and in dmso-d₆ show significant upfield shifts for the diethylammoniummethyl substituents, CH₂NH⁺(CH₂CH₃)₂, with respect to those of 1a (in CD₃OD: Δδ(CH₂CH₃) = 0.43, Δδ(CH₂CH₃) = 0.33, Δδ(CH₂N) = 0.25 ppm) whereas the chemical shifts of the other protons remain relatively unaffected (Δδ less than 0.15 ppm). The upfield shifts are similar to those reported by Corbellini et al. and point to partial inclusion of the diethylammoniummethyl substituents inside the hydrophobic cavity of the capsule.^6b A higher degree of encapsulation of these substituents was observed when the solvent polarity was increased by the addition of D₂O, as was evident from the larger upfield shifts.¶ A single set of proton resonances for the free and bound building blocks was observed in a temperature range of −40 to +50 °C (in CD₃OD), indicating a fast exchange process on the NMR time scale. Due to the fast exchange process the lower symmetry of the capsule compared to the calix[4]arene 2 (C₄v) is not apparent in the ¹H NMR spectra.¶^6a The capsule could also be prepared in situ by just mixing methanol (or dmso) solutions of 1a and 2 in the proper ratio. ¹H NMR titrations were carried out in CD₃OD (298 K) providing a stability constant of K_1a·2 = 6·10⁴ M⁻¹ for capsule 1a·2. The high association constant confirms that the diphosphine ligand 1a and the tetrasulfonatocalix[4]arene 2 indeed fit well to form a stable capsule. The titration curve fitted to a 1 ∶ 1 binding model is in line with the 1 ∶ 1 stoichiometry of the capsule, and a Job plot analysis of a titration experiment in CD₃OD proved indubitably the 1 ∶ 1 stoichiometry of capsule 1a·2 in solution. The 1D-NOESY spectrum of the heterodimeric capsule 1a·2 in CD₃OD displays significant negative intermolecular NOE contacts between the NH⁺(CH₂CH₃)₂ protons of 1a and the aromatic protons of 2.⁸ This illustrates that the aryl-substituents of the diphosphine ligand 1a and the upper rim of the calix[4]arene 2 are facing one another to form the typical dimeric 1 ∶ 1 capsular structure. The negative NOE enhancement confirms the large size of the capsule. Additional evidence for the formation of capsule 1a·2 was obtained by electrospray ionization mass spectrometry (ESI-MS).⁹ The positive-mode ESI-MS spectrum of 1a·2 in CH₃OH shows a prominent monoisotopic ion peak of the capsule at m/z 998.3 corresponding to [1a·2 + 2Na]²⁺. All the capsule's ion peaks correspond to 1 ∶ 1 complexes and no ion peaks for higher aggregates were detected. Moreover, comparison of the measured isotope pattern of 1a·2 with the calculated one confirms the elemental composition and charge state. The assignment of the capsule's ion peaks is in agreement with collision experiments.¶

Encapsulation of a neutral palladium metal inside the supramolecular capsule was achieved by using the neutral palladium complex 1b [(trans-1a)Pd(p-C₆H₄CN)(Br)] as the complementary building block for 2 (Fig. 1).^7b The neutral palladium complex 1b has a distorted square planar geometry with the oxygen atom of the ligand backbone in the apical position.^7c In spite of the higher rigidity of the palladium complex 1b compared to the free ligand 1a, molecular modeling study on capsule 1b·2 illustrates that 1b and 2 fit well and can form a capsule with the palladium metal located inside the capsule and the p-cyanophenyl group of 1b sticking out of the capsule. This p-cyanophenyl group of 1b is situated above the capsule equator and is not interfering with the assembly process. Indeed, mixing equimolar solutions of 1b and 2 in water led to the precipitation of capsule 1b·2 as a yellow solid. In contrast to capsule 1a·2, capsule 1b·2 is only sparingly soluble in methanol and dissolves well only in dmso. The diethylammoniummethyl protons of capsule 1b·2 exhibit high upfield shifts with respect to those of 1b (in dmso-d₆: Δδ(CH₂CH₃) = 0.41, Δδ(CH₂CH₃) = 0.27, Δδ(NH⁺) = 1.14 ppm), again pointing to partial inclusion of the alkyl tails. The 1D-NOESY spectrum of 1b·2 in dmso-d₆ shows significant negative intermolecular NOE contacts between the NH⁺(CH₂CH₃)₂ protons of 1b and the aromatic protons of 2, indicating that similar to 1a·2 the upper rim of the calix[4]arene is associated with 1b. The ESI-MS spectrum of capsule 1b·2 in CH₃OH shows a prominent monoisotopic ion peak of the capsule at m/z 719.6 corresponding to [1b·2 − Br + 2H]³⁺ (Fig. 2). Interestingly, capsule 1b·2 remains stable after Br⁻ dissociation from the palladium, and the corresponding ionic capsule detected by ESI-MS gives the same ion peaks as the capsule based on the cationic palladium complex 1c (vide infra).

Fig. 2 ESI-MS spectrum of capsule 1b·2 in CH₃OH (inset: measured isotope pattern).

Since many catalytic cycles involve a cationic palladium species as intermediate we were interested in the formation of capsules using the cationic palladium complex 1c [(trans-1a)Pd(p-C₆H₄CN)]⁺[CF₃SO₃]⁻.‡^7c This cationic palladium complex adopts a square planar geometry with the ligand acting as an η³ terdentate P,O,P ligand (Fig. 1). Molecular modeling of capsule 1c·2 illustrates that 1c and 2 fit nicely and that the palladium metal as well as the p-cyanophenyl group of 1c are located inside the capsule. Mixing equimolar solutions of 1c and 2 in methanol or dmso resulted in clear solutions of capsule 1c·2.|| Similar to capsules 1a·2 and 1b·2, the diethylammoniummethyl substituents of 1c·2 are partly inside the cavity as judged from the upfield shifts observed for these protons in the ¹H NMR spectra of 1c·2 (in CD₃OD: Δδ(CH₂CH₃) = 0.58, Δδ(CH₂CH₃) = 0.39, Δδ(CH₂N) = 0.17 ppm) (Fig. 3). Again, 1D-NOESY experiments confirm the proposed geometry of the dimeric capsule 1c·2 since significant negative intermolecular NOE contacts between the NH⁺(CH₂CH₃)₂ protons of 1c and the aromatic protons of 2 are observed. The ESI-MS spectrum of capsule 1c·2 in CH₃OH shows a prominent monoisotopic ion peak of the capsule at m/z 719.7 corresponding to [1c·2 − OTf + 2H]³⁺. Interestingly, the phosphorus chemical shifts of 1a, 1b and 1c did not exhibit a noteworthy shift upon capsule formation (Δδ < 0.6 ppm), indicating that the geometry around the phosphorus atoms did not change upon capsule formation.

Fig. 3 ¹H NMR spectra in CD₃OD. Top: 1c; Middle: capsule 1c·2 (1c/2 = 2/3); Bottom: 2. Asterisks indicate solvent signals.

¹H NMR titration experiments in CD₃OD at 298 K gave an association constant of K_1c·2 = 6·10³ M⁻¹ for capsule 1c·2 (1 ∶ 1 binding model), which is ten times lower than the association constant of capsule 1a·2. A plausible explanation is the poorer complementarity between 1c and 2. The more flexible free ligand 1a can adapt to the favoured geometry to optimize interactions with 2, whereas the Pd–aryl complex 1c is too rigid to do so. Additional evidence for this comes from diffusion-ordered NMR spectroscopy (DOSY). The diffusion coefficients D of the three capsules are lower than those of the corresponding free building blocks, confirming the larger size of the capsules (e.g.D_1c·2 = 2.04 and D_1c = 3.21 10⁻⁶ cm² s⁻¹).**¹⁰ More importantly, the diffusion coefficient of capsule 1c·2 is lower than that of capsule 1a·2 (D_1c·2 = 2.04 and D_1a·2 = 2.46 10⁻⁶ cm² s⁻¹), indicating that 1c·2 is larger than 1a·2. These results imply that the more rigid Pd-complex 1c fits less well on the calix[4]arene 2 than the free ligand 1a, which results in a bigger distance between 1c and 2 and hence a larger capsule.

Preliminary studies show that the metal center inside the capsule retains its reactivity. Bubbling carbon monoxide through a methanol solution of 1c·2 resulted in a quantitative insertion of CO in the Pd–aryl bond and yielded capsule 1d·2 (1d = [(trans-1a)Pd(C(O)p-C₆H₄CN)]⁺[CF₃SO₃]⁻).‡^11a,b The insertion of CO was fast and comparable to the insertion reaction in complex 1c (t_1/2 < 1 min) as expected for cationic palladium complexes.^11c,d The proton NMR spectrum of capsule 1d·2 confirms that the capsule remains intact upon CO-insertion. As found for other trans-coordinating palladium diphosphine complexes, capsule 1d·2 as well as complex 1d did not further react with methanol to provide the methanolysis product.^11c

In summary, we have introduced a simple strategy for the formation of a new type of metallocapsules, which is based on mixing solutions of functionalized diphosphine ligands (and the metal complexes thereof) and calix[4]arenes utilized with complementary groups. In the current example the assembly process is based on ionic interactions; the tetraammonium functionalized diphosphine ligand 1a or the metal complexes thereof readily associate with the tetraanionic calix[4]arene 2, forming supramolecular capsules as indicated by ¹H-NMR, 1D-NOESY and DOSY experiments, and ESI-MS. Encapsulation of these transition metals opens up new opportunities to control the activity, stability and selectivity of the potential homogeneous catalysts.

Notes and references

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Footnotes

† Electronic supplementary information (ESI) available: experimental details, Job plot, ¹H NMR titration, NOESY, DOSY and ESI-MS. See DOI: 10.1039/b518274c

‡ The counterions of ligand 1a in Pd-complexes 1c and 1d are CF₃SO₃⁻ instead of Cl⁻.

§ Chloride tests with silver nitrate show the presence of NaCl in the water filtrate and absence in the isolated capsule precipitate.

¶ The observations described for capsule 1a·2 were also found for capsules 1b·2 and 1c·2.

|| Compound 1c is not soluble in water.

** As the free and bound building blocks exchange fast on the NMR timescale, the observed D of the capsules are the weighted average of D of the free and bound building blocks.^10b

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