Pyridine-thiolate Titanocene Metalloligands and their Self-Assembly Reactions to Yield Early-Late Metallomacrocycles

New titanocene pyridine-thiolate compounds [(RCp) 2 Ti(4-Spy) 2 ] (R = H, 1 ; Me, 2 ) (Cp = cyclopentadienyl; 4-Spy = pyridine-4-thiolate) and [Cp 2 Ti(2-Spy) 2 ] ( 3 ) (2-Spy = pyridine-2-thiolate) have been prepared by reaction of the corresponding Li(Spy) salt with the appropriate compound [(RCp) 2 TiCl 2 ]. Compounds 1 - 2 have been used as metalloligands in self-assembly reactions with the acceptor late transition metal compounds [M(H 2 O) 2 (dppp)](OTf) 2 ( M = Pd, a ; Pt, b ) (dppp = 1, 3-bis(diphenylphosphino)propane) and a series of early-late tetranuclear metallomacrocycles [{(RCp) 2 Ti(4-Spy) 2 }{M(dppp)}] 2 (OTf) 4 (R = H, M = Pd ( 1 2 a 2 ); R = H, M = Pt ( 1 2 b 2 ); R = Me, M = Pd ( 2 2 a 2 ); R = Me, M = Pt ( 2 2 b 2 )) arising from the anti isomer of the titanocene metalloligands have been obtained. Only ligand transfer reactions from Ti to either Pd or Pt atoms have been observed when the pyridine-2-thiolate derivative 3 has been assayed in self-assembly processes. The obtained species have been characterized by NMR spectroscopy and ESI(+) mass spectrometry. The supramolecular assemblies have shown to be non-rigid in solution and their fluxional behavior has been


Introduction
The design and synthesis of multi-nuclear discrete coordination architectures and polymeric coordination networks has been a major focus of coordination and metallosupramolecular chemistry over the past decades. 1 The most interesting multimetallic coordination architectures are to be found in closed, geometrically-shaped 2D and 3D architectures including triangles, squares, rectangles, trigonal prisms, boxes, tetrahedra, polyhedral cages, and so forth. 2 The synthesis of heterometallic supramolecular assemblies is of great interest because the coexistence of different metal atoms into the complexes may provide singular topologies or create unusual metal coordination environments that may influence the properties of the assemblies, such as catalysis, 3 electrochemistry, 4 luminescence, 4c, d, 5 or magnetic behaviour. 6 In this context, early-late heterobimetallic assemblies have the potential to act as multifunctional catalysts for mechanistically different chemical reactions owing to the interplay of widely electronically divergent transition metals. The combination of a Lewisacidic early transition metal and an electron-rich late transition metal is expected to promote unusual reactivity patterns due to possible synergistic effects and cooperativity arising from the simultaneous or consecutive action of different metal centers. 7 Although fragmentation has been considered a major drawback of the multimetallic catalysts, heterometallic supramolecular assemblies can also behave as a reservoir of unsaturated highly reactive species otherwise not accessible with single catalysts. 8 Comparison of the well-established supramolecular chemistry of late transition metals such as palladium or platinum with that of early transition metals (mainly titanium or zirconium) reveals that only a limited number of attempts have been made to incorporate in the metallomacrocyclic core metal fragments containing early transition metals. 9 In particular, to connect different early-and late transition-metal fragments in a single molecule in order to form a heteromulti-metallic assembly is from the synthetic viewpoint, a challenge because the formation of well-shaped metallomacrocyclic compounds usually requires the design of ligands able to accommodate the different electronic and coordination environments of both dissimilar metals. Remarkably, the incorporation of flexible mixeddonor ligands having ambivalent hard-soft character that selectively binds to distinct metals allows for the successful synthesis of d 0 -d 8 early-late metallomacrocycles circumventing the geometrical and electronic requirements. Thus, some examples of early-late metallomacrocycles have been assembled using the hard/soft acid-base rule (HSAB) as a design principle.
For example, [Ti 2 Pt 2 ] tetranuclear metallomacrocycles have been successfully assembled using a ditopic bis(pyridine-carboxylate) moiety (Chart 1a), 10 and [(Ti or Zr) 2 -(Rh or Ir) 2 ] tetrametallic species have been prepared by using either titanocene or zirconocene moieties containing flexible alkoxyphosphino ligands in which the pendant phosphines are bound to the late metals after the self-assembly process (Chart 1b). 11 The amidophosphine [(Bu t 2 CH)N(C 6 H 4 )PPh 2 ]has been successfully used as linker in the synthesis of binuclear Hz) for the α and β protons of the pyridine rings of the equivalent pyridine-4-thiolato ligands.
The equivalent cyclopentadienyl ligands in 1 were observed at δ 6.09 and 113.2 ppm in the 1 H and 13 C{ 1 H} NMR spectrum, respectively. However, the equivalent methylcyclopentadienyl ligands of 2 give rise to two virtual triplets at δ 5.74 and 5.59 ppm for the cyclopentadienyl protons and a singlet a δ 1.79 ppm for the methyl substituent in the 1 H NMR spectrum.
Moreover, the 13 C{ 1 H} NMR spectrum also shows two resonances (δ 115.1 and 113.4 ppm) for the CH of the MeCp rings, which suggests both free rotation of the pyridine-4-thiolato 8 ligands about the Ti-S bond and the MeCp ligands and, thus resulting in a effective C 2v symmetry.
However, compound 3 was isolated directly from the reaction media due to its low solubility in THF and obtained as a red microcrystalline solid in 59 % yield. The MS (EI+) spectrum of 3 showed the most intense peak at m/z 333, which correspond to the loss of a Cp ring from the molecular ion. In addition , 1 H NMR ( Figure S3 in Supporting Information) and 13 C NMR spectra show equivalent Cp and 2-Spy ligands, which is in full agreement with the proposed structure (Scheme 1). In contrast to 1 and 2 that are moderately stable on air in the solid state, In fact, DFT calculations on the stability of complexes 1 and 3 (Scheme 1) have shown that both complexes are 33.1 and 27.4 kcal/mol more stable respectively, than the corresponding isomers featuring kS coordinated pyridine-thiolato ligands (Table S1 in Supporting Information). In this context, it is worth mentioning that a number of tetrahedral metallocene thiolate-titanium [Cp 2 Ti(SR) 2 ] (R = Me, Ph, …) 20 complexes have been structurally characterized.

Self-Assembly Reactions: Topological Considerations. The titanocene complexes 1-3
having pyridine-thiolato ligands feature two peripheral pyridine nitrogen-donor atoms and consequently could be utilized as ditopic building blocks in the preparation of early-late coordination-based supramolecular assemblies. Due to the high flexibility of the ligand an analysis of the possible conformations of the titanocene complexes is required to assess about the possibility of achieving the synthesis of the targeted metallomacrocycles by combination with cis-blocked square-planar late metal complexes.
Assuming an anti disposition orientation of the terminal 4-pyridyl groups in the metallocene complexes 1 and 2, the non-bonding sp 2 orbitals of the N atoms are oriented in a divergent fashion, thus allowing the formation of discrete supramolecular assemblies by combination with 90° acidic metal fragments ( Figure 1a). In the case of a syn orientation of the pyridyl groups (Figure 1b), the parallel disposition of the nitrogen sp 2 orbitals makes possible (by reaction with 90º metal acceptor fragments) the formation of well-defined tetranuclear species. In contrast, the location of the nitrogen-donor atoms in metallocene complex 3, adjacent to the S-donor atoms, only can produce the assembly of discrete tetranuclear architectures when both terminal 2-pyridyl groups are anti-oriented ( Figure 1c).
However, free rotation about the S-C results in a syn positioning of both groups allowing the chelation to only one cis-blocked square-planar acceptor fragment. In this case, the formation of dinuclear early-late heterobimetallic species could be envisaged ( Figure 1d).
Moreover, it is important to note that the orientation of the donor moieties in all the conformations adopted by these metalloligands along with their conformational flexibility makes also possible the formation of self-assembled polymeric species such as infinite chains or networks by combination with the indicated acceptor units.  can be found in Figure S7 in Supporting Information).
The 31 P{ 1 H} NMR spectrum in nitromethane-d 3 displayed a singlet at δ ≈ 4.9 ppm for the palladium macrocycles 1 2 a 2 and 2 2 a 2 ( Figures S8 and S9 singlet at δ ≈ -16.9 ppm flanked by platinum satellites ( 1 J Pt-P ≈ 2990 Hz) for the platinum species 1 2 b 2 and 2 2 b 2 (Figures S10 and S11 in Supporting Information). The upfield shift of the 31 P NMR signals together with the significant decrease in the value of the 1 J Pt-P coupling constant evidenced the coordination of the pyridine rings to either the palladium or platinum centers. 21 On the other hand, the chemical equivalence of both the dppp ligands and the phosphorus atoms within the bidentate ligands is indicative of a highly symmetrical structure.
The 1 H NMR spectrum of the macrocycles [{Cp 2 Ti(4-Spy) 2 }{M(dppp)}] 2 (OTf) 4 (M = Pd, 1 2 a 2 ; Pt, 1 2 b 2 ) in nitromethane-d 3 at RT showed featureless resonances for the aromatic and >CH 2 protons of the dppp ligands evidencing a fluxional behavior (Figures S12 and S13 in Supporting Information). In addition, whereas one rather broad signal appeared for the α and β protons of the 4-pyridyl groups a sharp resonance at δ ≈ 6 ppm could be assigned to the protons of the four cyclopentadienyl ligands.
The assemblies [{(MeCp) 2 Ti(4-Spy) 2 }{M(dppp)}] 2 (OTf) 4 (M = Pd, 2 2 a 2 ; Pt, 2 2 b 2 ) also exhibited broad resonances in their 1 H NMR spectra (nitromethane-d 3 , RT) although it is remarkable that four broad resonances in the range δ 6.3-5.6 ppm were observed for the unequivalent CH protons of the methylcyclopentadienyl ligands but only a singlet a δ ≈ 2 ppm appears for the methyl substituent (Figures S14 and S15 in Supporting Information). As can be seen in Figure 3 for compound 2    Information) and the energy difference obtained was 5.8 kcal/mol (Table S1 in Supporting Information). Taking into account the presence of two {Cp 2 Ti(4-Spy) 2 } fragments in the metallomacrocycle most of the destabilization of the C 2v structures is caused by the syn conformation of the terminal 4-pyridyl groups. On the other hand, it is remarkable that the C 2h isomer of the metallomacrocycle 1 2 b 2 has been calculated to be 50.6 kcal/mol more stable than the corresponding isomer resulting from the coordination of the pyridine-4-thiolato ligands to the titanium and platinum centers through the N and S donor atoms, respectively, which is in full agreement with the marked stability of the metalloligand having kS coordinated ligands. Ti(4-Spy) 2 }{Pt(dppp)}] 2 4+ metallomacrocycle (1 2 b 2 ) (see Figure 5, above C 2h , middle D 2 and below C 2v ), see equivalent figure for the Pd II compound (1 2 a 2 ) in Figure S20. Also cartesian coordinates and energies are provided as Supporting Information). Large grey, large blue, yellow, gray, blue and black spheres correspond to platinum, titanium, sulfur, phosphorus, nitrogen, carbon atoms, respectively.
In order to study the aforementioned fluxional behavior displayed by the metallomacrocyclic species, we performed molecular dynamic simulations at 300 K (see Computational details section). The variation of the metal-ligand bond distances during the simulation is depicted in Figure S21. At first glance, the changes in the bond distances are slightly larger for the Pd II compound than for the Pt II system (see the movie of the simulations as Supporting Information) in agreement with the larger fluxionality found experimentally in the Pd II metallomacrocycles in comparison with those holding a Pt II metal center. After the initial thermalization process, the analysis of the metal-ligand bond distances of the 4-Spy ligand shows a broad variation range for the Ti-S bond distances, from 2.3 to 2.8 Å for the Pt II systems and even wider for the Pd II case, i. e. from 2.1 to 3.0 Å ( Figure S21 in Supporting Information). The results of the simulation should indicate a larger tendency of the Ti-S bond to undergo coordination-decoordination processes than the Pt(Pd)-N py bonds. Such tendency would also facilitate the interconversion between the two more stable isomers, namely the C 2h and D 2 structures, because this corresponds to the interchange of positions of the two sulfur atoms coordinated to one Ti center. This may be a consequence of the hard-soft mismatch between the hard early transition metal and the soft sulfur donor atom, which most likely is the driven force for the ligand transfer reactions (see below) and could be also responsible for the high air and water sensitivity of the metallomacrocycles.  The supramolecular assemblies are non-rigid in solution, which is compatible both with the high flexibility of the metallomacrocycles or/and a coordination-decoordination process involving metal-ligand bonds. In this context, molecular dynamic simulations have revealed that the Ti-S bonds exhibit a larger tendency than the M-N py (M = Pd, Pt) bonds to undergo coordination-decoordination processes, which may be a consequence of the hard-soft mismatch between the hard early transition metal and the soft sulfur-donor atom.