A twist on a classic scaffold: rational design of a new bimetallic platform

Abstract

Herein, we report the synthesis of a modular family of novel bimetallic tetraamidodiamine (tada) ligands, Li₄-R-tada (R = Me₃Si, ^tBuMe₂Si, and ⁱPr₃Si). These silylamido ligands display two distinct binding pockets whose steric profiles can be easily tuned by choice of the substituents on silicon. We also show that salt metathesis is a convenient route to install these new ligands on the early transition metals titanium(IV) and vanadium(III).

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Some of the most powerful transformations in nature are made possible through the action of catalysts featuring multimetallic active sites. For instance, soluble methane monooxygenase (sMMO), a diiron enzyme found in methanotropic bacteria, can convert methane to methanol under ambient conditions,¹ a remarkable process that has yet to be replicated synthetically. Despite the key roles that these multimetallic species play, detailed studies on their mechanisms of action remain rare, in part because of the difficulties associated with studying such complex systems. Thus, it is of interest to examine simple, well-defined models of these active systems to gain valuable insights into how they function.^2,3 These data can then be used to rationally design subsequent generations of improved catalysts.

In order to isolate the effects of metal–metal interactions on reactivity, we sought to prepare a new binucleating ligand scaffold that closely mirrored a well-studied, monometallic congener in which the primary coordination sphere would be conserved. We identified the tris(2-aminoethyl)amine (tren) framework as a promising candidate for this study. The triply-silylated tren derivative (Me₃SiNHCH₂CH₂)₃N was first reported by Verkade in 1989,⁴ where its original use was to stabilize Group 14 compounds. Several years later, Cummins and Schrock demonstrated that the trianionic form of above silylamine was an excellent ligand for early transition metals (see Scheme 1, left).^5–7 The silyl groups of the metal complexes are oriented such that they create an accessible binding pocket at the axial coordination site opposite the tertiary amine donor atom. The substituents on the silyl also provide sufficient steric protection to prevent bimolecular decomposition while still allowing easy access to the transition metal for small molecule substrates. An appealing feature of this triamidoamine platform is that the substituents are highly variable, allowing for a wide degree of both steric and electronic tuning. We reasoned that a tetraamidodiamine (tada) analogue of such a ligand would be an appealing platform to enforce a bimetallic active site and allow for in-depth study of metal–metal interactions. Indeed, during the course of our studies reported here, Zhang, Hong, and Shi reported a binucleating, aryl-substituted tada ligand scaffold that could be applied towards dinitrogen activation with titanium (see Scheme 1, right).⁸ Interestingly, the authors reported successful C–H amination of the ligand backbone, which they propose occurs via a nitridyl intermediate.

Scheme 1 Literature examples of triamidoamine and tetraamidodiamine complexes.

We selected hexaamine 1 (see Scheme 2) as a promising candidate upon which to construct our targeted binucleating ligand motif. Despite being known in the literature since 1952,⁹ only a few groups have made use of 1 as a ligand building block.^10–13 Inspired by previous work from Verkade¹⁴ and Scheer,¹⁵ we found that the neopentyl-substituted ligand precursor H₄-Np-tada (2, Np = neopentyl) could be prepared smoothly in a two-step, one-pot reductive amination procedure of 1 with 4 equivalents of pivaldehyde. Compound 2 was isolated as a colourless oil in moderate yield (53%) and was fully characterized by NMR spectroscopy and high-resolution mass spectrometry. With 2 in hand, we next sought to explore its coordination chemistry. Following the examples of Schrock⁶ and Zhang, Hong, and Shi,⁸ we sought to coordinate our new scaffold to early transition metals. Treatment of THF solutions of 2 with 4 equivalents of ⁿBuLi resulted in a change from colourless to pale yellow. Subsequent addition of 2 equivalents of bright yellow TiCl₄(THF)₂ results in a rapid colour change to dark red-brown. After removal of the volatiles in vacuo, the dark brown residue was extracted with hexane, filtered, and dried again to yield an orange-brown powder. Analysis by ¹H NMR spectroscopy revealed a single major product (Np-tada-Ti, compound 3), and recrystallization of the crude product could be achieved by cooling a saturated hexane solution to −35 °C overnight, resulting in the deposition of orange-red crystals suitable for X-ray diffraction. The solid-state structure of compound 3 is shown in Fig. 1. The complex is monometallic, with the titanium(IV) center adopting an octahedral geometry featuring both amine and all four amido donors from the ligand. We reasoned that larger substituents on the amido nitrogens would be required to open up the binding pocket to preferentially accommodate two metals. Historically, silylated triamidoamine ligands have been successfully utilized by several groups, including Schrock,^5–7,16 Filippou,^17,18 and Liddle.^19,20 Following a modification of the procedure developed by Schrock, hexaamine 1 was suspended in THF and treated with 4 equivalents of ⁿBuLi, followed by the addition of 4 equivalents of R₃SiCl (R₃ = Me₃, ^tBuMe₂, or ⁱPr₃, see Scheme 3). Following removal of the volatiles in vacuo and extraction with hexane, filtration through Celite yielded pale yellow solutions, which were subsequently treated with another 4 equivalents of ⁿBuLi. After solvent removal and recrystallization, compounds R-tada-Li₄ (R = Me₃Si (4), R = ^tBuMe₂Si (5), and R = ⁱPr₃Si (6)) could be isolated as colourless crystals in good yields. All three compounds were characterized by ¹H and ¹³C NMR spectroscopy, as well as by diffraction studies. X-ray quality crystals of compounds 4 and 5 were grown from THF/hexane at −35 °C, while suitable crystals of 6 were grown by cooling a saturated hexane solution. The solid-state structures are shown in Fig. 2. All three of the complexes show two binding pockets that each contain external (κ²) and internal (κ³) Li centers. The structures of 4 and 5 are very similar, with each Li being bound by a single THF molecule. In contrast, compound 6 only features THF bound to the two κ² Li centers (see Fig. 2). We attribute this to the increased steric hindrance of the bulky ⁱPr₃Si groups. The binding pockets of all three complexes can be considered as more open, dianionic analogues of the commonly used triazacyclononane (tacn) family of ligands.

Scheme 2 Synthesis of compound 2 and complex 3. Isolated yields in parentheses.

Fig. 1 Solid-state structure of 3 (50% probability ellipsoids). All hydrogen atoms omitted for clarity.

Fig. 2 Solid-state structures of 4 (left), 5 (middle), and 6 (right), all with 50% probability ellipsoids. All hydrogen atoms omitted for clarity.

Scheme 3 Synthesis of tetralithium complexes 4, 5, and 6. Isolated yields in parentheses.

We next sought to explore the coordination chemistry of 4–6 with early transition metals. Unfortunately, while each lithiated ligand precursor did react with either TiCl₄(THF)₂ or TiCl₃(THF)₃, as indicated by rapid colour changes, characterization of the products has been hindered by the broadness of the peaks observed in the ¹H NMR spectra, as well as the significant solubility of the products in organic solvents. Fortunately, switching to a different titanium(IV) precursor results in more tractable product formation. Addition of 5 to a yellow solution of [(tmeda)Ti(N^tBu)Cl₂]²¹ (tmeda = N,N,N′,N′-tetramethylethylenediamine) in THF along with gentle heating (50 °C) results in a colour change to orange-red. Analysis by ¹H NMR spectroscopy reveals the formation of a new symmetric product, ^tBuMe₂Si-tada-[Ti(N^tBu)(THF)]₂ (7, see Scheme 4) in 60% spectroscopic yield. Attempts to isolate compound 7 in pure form were hindered by its decomposition to multiple unidentified species during workup and recrystallization. Nevertheless, we were able to obtain orange-red crystals from these attempts which were suitable for diffraction analysis. The solid-state structure of 7 is shown in Fig. 3. Gratifyingly, the complex demonstrates successful incorporation of one metal into each of the binding pockets. Like the tetralithium complexes 4–6, the structure of 7 is centrosymmetric. The coordination geometry at titanium is a distorted square pyramid, with the imido moiety occupying the apical position. The last coordination site is filled by a THF ligand.

Scheme 4 Synthesis of complex 7. ¹H NMR spectroscopic yield in parentheses.

Fig. 3 Solid-state structure of complex 7 (50% probability ellipsoids). All hydrogen atoms omitted for clarity.

The structure of 7 reveals no metal–metal interactions, which is unsurprising given the d⁰–d⁰ configuration. To probe whether an increase in the d-electron count or the presence of potentially bridging chloride ligands would lead to observable metal–metal interactions in these complexes, we next turned our attention to vanadium(III). Stirring THF solutions of either 5 or 6 with 2 equivalents of VCl₃(THF)₃ resulted in colour changes from maroon to a dark red-brown or purple, respectively. Complexes ^tBuMe₂Si-tada-[VCl]₂ (8) and ⁱPr₃Si-tada-[VCl]₂ (9, see Scheme 5) were both isolated from their respective reaction mixtures by extraction with hexane, and X-ray quality crystals of each were grown by cooling saturated hexane solutions to −35 °C overnight. The solid-state structures are shown in Fig. 4. Complex 8 crystallizes as an intermolecular coordination polymer, with the V–Cl moiety of one binding pocket coming together with that of another molecule of 8 to form a V₂Cl₂ diamond linkage, which daisy chains along the polymer backbone. Related geometries at vanadium(III) have been observed by Cloke²² and Gambarotta,²³ The V–V distance across the V₂Cl₂ diamondoid in 8 is 3.7161(9) Å, slightly longer than the corresponding distance in the crystallographic data reported by Gambarotta.²³ In contrast, the solid-state structure of 9 is monomeric, with each metal center adopting a distorted trigonal monopyramidal geometry. Like complex 7, the solid-state structure of 9 is centrosymmetric. While 8 shows a substantially different coordination environments from the vanadium(III) tren complex reported by Schrock,⁶ complex 9 displays a similar trigonal monopyramidal geometry We attribute the structural differences between 8 and 9 to the increased steric profile of the ⁱPr₃Si groups. To quantify the importance of steric effects in these tada systems, we turned to buried volume (V_bur).^24,25 Not surprisingly, the monometallic complex 3, which is coordinatively saturated with the tada ligand and essentially binds both binding pockets, has a buried volume of 96.7%. The tada ligands of complexes 7 (V_bur = 73.7%), 8 (V_bur = 87.8%) and 9 (V_bur = 83.2%), on the other hand, display only marginally lower buried volumes despite consisting of a single binding pocket per metal center. Evans method analysis of 8 and 9 reveals solution-state effective magnetic moments of 3.4μ_B and 3.6μ_B per bimetallic complex, respectively. The observed values are higher than that observed for Cloke's V₂Cl₂ dimer,^22,23 and may indicate a degree of antiferromagnetic coupling between the two (d²) vanadium(III) centers. Similar coupling has recently been observed with dititanium.²⁶ Neither 8 nor 9 reacted with 2 equivalents of Et₄NCl in THF at room temperature, as shown by UV/Vis spectroscopy. Further studies to coordinate these new multimetallic ligands to other transition metals, as well as exploring new oxidation states that may enable discrete metal–metal interactions, are ongoing in our laboratory.

Scheme 5 Synthesis of complexes 8 and 9. Isolated yields in parentheses.

Fig. 4 Solid-state structures of complex 8 (left, 40% probability ellipsoids) and complex 9 (right, 50% probability ellipsoids). All hydrogen atoms omitted for clarity. The silyl substituents of 8 are in wireframe.

Conclusions

This report details the synthesis and structural characterization of three new lithiated tetraamidodiamine (tada) ligands. These silylamido ligands display two distinct binding pockets whose steric profiles can be easily tuned by choice of the substituents on silicon. Preliminary reactivity studies demonstrate successful coordination of these new ligands to titanium(IV) and vanadium(III) via salt metathesis.

Author contributions

The manuscript was written through contributions of all authors. All authors have agreed to the final version of the manuscript.

Data availability

The experimental data generated in this manuscript are included in the ESI,† including experimental protocols, ¹H and ¹³C NMR spectroscopic data, mass spectrometry data, elemental analysis data, and X-ray Crystallographic data.

Crystallographic data for compounds 3–9 has been deposited at the CCDC under deposition numbers 2365242–2365248† and can be obtained from https://www.ccdc.cam.ac.uk/structures/?

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was supported by start-up funds from Oregon State University. We acknowledge the support of the Oregon State University NMR Facility funded in part by the National Institutes of Health, HEI Grant 1S10OD018518, and by the M. J. Murdock Charitable Trust grant #2014162. We also acknowledge the M. J. Murdock Charitable Trust (grant SR-2017297) for acquisition of OSU's single crystal diffractometer. We thank Prof. Chong Fang for use of his UV/Vis spectrophotometer.

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Footnote

† Electronic supplementary information (ESI) available. CCDC 2365242–2365248. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d4dt01840k

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