Heterogeneously catalyzed thioether metathesis by a supported Au–Pd alloy nanoparticle design based on Pd ensemble control

C–S bond metathesis of thioethers has gained attention as a new approach to the late-stage diversification of already existing useful thioethers with molecular frameworks intact. However, direct or indirect thioether metathesis is scarcely reported, and heterogeneously catalyzed systems have not been explored. Here, we develop heterogeneously catalyzed direct thioether metathesis using a supported Au–Pd alloy nanoparticle catalyst with a high Au/Pd ratio. The Au-diluted Pd ensembles suppress the strong π-adsorption of diaryl thioethers on the nanoparticles and promote transmetalation via thiolate spill-over onto neighboring Au species, enabling an efficient direct thioether metathesis.


Introduction
Multimetallic nanocatalysts can exhibit higher catalytic performance and/or selectivity than their monometallic counterparts.This high performance is usually attributed to three alloy effects-ensemble, ligand, and strain effects 1 -which are difficult to study in isolation.Nevertheless, according to some reports, the dominant effect is metal ensembles on the nanoparticle surfaces.1a The decreased ensembles of active metal species alter the adsorption conguration of molecules 2 or exhibit a single atom-like character, 3 resulting in unique catalytic properties.Such catalyst designs based on ensemble control are uniquely applicable to nanoparticle catalysts and have the potential to realize novel molecular transformations.
Diaryl thioethers are widely used in polymers, natural products, bioactive compounds, and pharmaceuticals.4a-c Latestage diversication of diaryl thioethers, which enables functionalization and transformation of complex molecules without disrupting their building blocks, has therefore become an important goal in synthetic organic chemistry, medicinal science, and materials science. 4One desirable approach is C-S bond metathesis of diaryl thioethers, which synthesizes novel diaryl thioethers from already existing useful thioethers.The rst C-S bond metathesis of diaryl thioethers was reported by Morandi et al., 5a who also constructed porous organic polymers with two-and three-dimensional cores under mild reaction conditions (∼80 °C) using a homogeneous Pd complex catalyst.5b Theoretically, direct C-S bond metathesis of diaryl thioethers can proceed through the following catalytic cycle: adsorption and oxidative addition of thioethers to Pd species, transmetalation between oxidative adducts, and then reductive elimination and desorption of thioethers from Pd species (Scheme 1a).However, the direct metathesis does not occur in their reports 5a,b possibly because the transmetalation step is prohibitively difficult on Pd complex catalysts.Thus, thiols and lithium bis(trimethylsilyl)amide are required for their reaction systems: indirect C-S/C-S cross-metathesis via C-S/S-H metathesis between diaryl thioethers and thiols (Scheme 1b). 5 Quite recently, Audisio et al. reported Ni-catalyzed direct C-S/C-S cross-metathesis of various thioethers for isotope labelling without using thiols and bases; 6 however, C-S bond metathesis of diaryl thioethers was not demonstrated.On the other hand, recently, we achieved the rst example of direct C-S bond metathesis of diaryl thioethers using only Pd acetate and tricyclohexylphosphine (PCy 3 ) as catalyst precursors. 7The active species of metathesis was conrmed as in situ-formed Pd nanoclusters, which likely enable direct crossover between two oxidative adducts (Scheme 1c).However, heterogeneously catalyzed C-S bond metathesis of diaryl thioethers, including indirect metathesis, is demanded for practical use and green sustainable chemistry but has not been attained.In fact, supported monometallic Pd nanoparticles hardly catalyze C-S bond metathesis between phenyl sulde (1a) and p-tolyl sulde (1b), even with PCy 3 (Table S1 †). 7Clearly, an additional catalyst design is required for heterogeneously catalyzed thioether metathesis.
This study proposes a heterogeneously catalyzed efficient direct C-S bond metathesis of diaryl thioethers using a TiO 2 -supported Au-Pd alloy nanoparticle catalyst (Au 4.4 -Pd 1 /TiO 2 ) without any additives (Scheme 1d).This catalytic system exhibits a wide substrate scope and functional group tolerance; moreover, the catalyst can be reused a few times.Catalyst characterization and density functional theory (DFT) calculations of cluster models showed that when the Pd ensembles are diluted by Au alloying, the changed adsorption mode of thioethers on the nanoparticles lowers the adsorption/desorption energy and enables C-S bond metathesis.We also suggest that oxidative addition of thioethers produces thiolate species on the Pd species, which migrate to the Au species and promote the transmetalation step, thereby achieving efficient thioether metathesis.The Pd K-edge and Au L III -edge X-ray absorption near edge structure (XANES) spectra of Au 4.4 -Pd 1 /TiO 2 were similar to those of Pd foil and Au foil, respectively (Fig. 1a and b), indicating zero valence of Pd and Au, as inferred from the Pd 3d and Au 4f X-ray photoelectron spectra of Au 4.4 -Pd 1 /TiO 2 (Fig. S1 †).From high-angle annular dark-eld-scanning transmission electron microscopy (HAADF-STEM) images, the mean diameter of the TiO 2 -supported metal nanoparticles was determined as 3.05 nm (s = 0.77 nm; Fig. 1c and d).From the almost coincident locations of Pd and Au species in the STEM-energydispersive spectroscopy (EDS) mapping of Au 4.4 -Pd 1 /TiO 2 (Fig. 1e-g) and the tting of the Pd K-edge and Au L III -edge extended X-ray absorption ne structure spectra (indicating that the scatterings originated from Au-Pd bonds; see Fig. S2 and Table S2 †), we inferred that Au-Pd alloy nanoparticles were supported on TiO 2 .Moreover, the X-ray diffraction (XRD) patterns of Au 4.4 -Pd 1 /TiO 2 and TiO 2 were comparable (Fig. 1h), conrming that the TiO 2 structure was unchanged during the catalyst preparation.

Results and discussion
Table 1 lists the reaction conditions for investigating the effect of Pd-based supported nanoparticle catalysts on C-S bond metathesis between 1a and 1b.A quantitative metathesis can obtain two equivalents of phenyl p-tolyl sulde (1ab) on the basis of 1b.Based on our previous report, 7 we rst investigated a monometallic TiO 2 -supported Pd nanoparticle catalyst but 1ab was hardly obtained (Table 1, entry 1).‡ Among several TiO 2supported Pd-based bimetallic nanoparticle catalysts, the Au-Pd alloy nanoparticle catalyst exhibited the highest catalytic performance for C-S bond metathesis (Table S3 †).We therefore prepared supported Au-Pd alloy nanoparticle catalysts with various Au/Pd ratios (Au x -Pd 1 /TiO 2 , x: Au/Pd molar ratio).The catalytic performance of metathesis improved with increasing Au/Pd ratio in the catalyst, reaching a 1ab yield of 55% for Au 4.4 -Pd 1 /TiO The C-S bond metathesis of 1a and 1b immediately ceased aer hot ltration of Au 4.4 -Pd 1 /TiO 2 (Fig. S3 †), and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) detected almost zero Pd and Au species in the ltrate (Pd: below the detection limit, Au: 0.004% of the Au used in the reaction).Therefore, the observed catalysis was truly heterogeneous.Although the catalyst could be regenerated via calcination in an air followed by reduction with NaBH 4 and reused twice without signicant loss of the nal yield (Fig. S4 †), the nal 1ab yield dropped at the 4th use.The average size of Au-Pd nanoparticles in the Au 4.4 -Pd 1 /TiO 2 aer the 1st use observed by HAADF-STEM (d = 3.70 nm, s = 1.12 nm) was a little larger than that of the fresh catalyst (d = 3.05 nm, s = 0.77 nm) (Fig. 1c, d, and S5 †), and a new peak assigned to Au(111) appeared in the XRD pattern of the catalyst aer the 4th reuse (Fig. S6 †),  indicating that the aggregation of Au-Pd nanoparticles is one reason for the deactivation of the catalytic activity.Scheme 2a summarizes the substrate scope of Au 4.4 -Pd 1 / TiO 2 -catalyzed C-S bond metathesis of diaryl thioethers.§ Symmetrical methyl-substituted thioethers at the para, meta, and ortho positions afforded the corresponding unsymmetrical thioethers in good yields (1ab-1ad).Other electron-donating groups, including 4-tert-butyl and 4-methoxy groups, also afforded their metathesis products (1be, 1af).This system is applicable to thioether metathesis with electron-withdrawing triuoromethyl groups (1ag, 1ah) and halogenated thioethers with uoro and chloro groups (1bi, 1bj).4-Biphenyl-, 2-naphthyl-, and 4-pyridyl-substituted thioethers also served as competent metathesis partners (1bk, 1bl, 1am).Thioethers with amino (1an), N,N-dimethylamino (1bo), cyano (1bp), nitro (1aq), acetamide (1br), methyl ester (1bs), and acetyl (1bt) functional groups were converted into the corresponding unsymmetrical thioethers without disrupting the functional groups.Moreover, commercial polyphenylene sulde (PPS, 1a 0 ) decomposed into 1,4-bis[(4-methylphenyl)thio]benzene (1bab) via metathesis between 1a 0 and 1b in the presence of Au 4.4 -Pd 1 /TiO 2 (Scheme 2b).Gram-scale synthesis from 1a and 1f afforded the metathesis product 1af (1.10 g, 63% isolated yield) (Scheme 2c).
The effect of alloying on the present C-S bond metathesis of thioethers was determined from diffuse reectance infrared Fourier transform (CO-DRIFT) spectra of adsorbed CO on Au 1.6 / TiO 2 , Pd 1 /TiO 2 , and Au x -Pd 1 /TiO 2 (Fig. 2a).In the CO-DRIFT spectra of Pd 1 /TiO 2 , Au 0.7 -Pd 1 /TiO 2 , and Au 1.4 -Pd 1 /TiO 2 , which exhibited low catalytic activity for the C-S bond metathesis (Table 1, entries 1-3), three peaks around 2070, 1980, and 1920 cm −1 were observed assignable to linear (B), bridged (C), and three-fold (F) CO species on zero-valent Pd species, respectively. 9In the CO-DRIFT spectra of Au 3.0 -Pd 1 /TiO 2 and Au 4.4 -Pd 1 /TiO 2 showing high catalytic activity (Table 1, entries 4 and 5), peaks C and F were absent while new peaks at 1950 and 1940 cm −1 were attributable to CO species bridged on Au and Pd species (D) and on Pd species surrounded by Au species (E), respectively.9d As the Pd and Au-Pd alloy nanoparticles were similarly sized (Fig. 1c, d and S7 †) and the peak of the CO species on Pd did not shi with increasing Au/Pd ratio in Au x -Pd 1 /TiO 2 (Fig. 2a), we attributed the high catalytic activity of Au 4.4 -Pd 1 /TiO 2 to the diluted Pd ensembles rather than to the ligand effect.
Next, the ensemble effect on the present C-S bond metathesis was investigated through DFT calculations on Pd 20 and Au 18 Pd 2 cluster models.Referring to previous reports, we adopted Gaussian 16 (M06 functional with SDD basis sets for Au and Pd and 6-31G(d,p) basis sets for H, C, and S) 10 (see ESI for the calculation methods and model selection) (Fig. S8-S10).† The adsorption Gibbs energy of 1a was calculated at the center site of the Pd 20 or Au 18 Pd 2 cluster model.{The adsorption Gibbs energy of 1a on Pd 20 is very high (DG = −48.3kcal mol −1 ), indicating that the metathesis product cannot easily desorb and the reaction is strongly inhibited (Fig. 2b).In contrast, 1a adsorbed on Au 18 Pd 2 has a moderate DG(−24.7 kcal mol −1 ) and the reaction can proceed (Fig. 2c).The optimized structure of 1a on Pd 20 claries strong p-adsorption between 1a and the Pd 20 facets, whereas 1a on Au 18 Pd 2 adheres via coordination of its S atom to the Pd center with almost no p-adsorption.Corroborating this nding, the natural-bond orbital charge of the phenyl group is higher in Pd 20 -adsorbed 1a than in free 1a, probably due to p-back donation from the Pd species to the phenyl rings of 1a, 11 but is lower in Au 18 Pd 2 -adsorbed 1a than in free 1a, possibly due to s-donation from the S atom to the Pd atom (Fig. S11 †).Facilitated by the weak p-back donation ability of the Au species, 12 the Pd ensembles diluted with Au alloy changed the 1a adsorption mode and lowered the adsorption energy to enable the reaction (Scheme 1d).kMoreover, as indicated in the optimized structure of 1a oxidative adducts to Au 18 Pd 2 (Fig. S12 and S13 †), the thiolate species produced by thioether oxidative addition on Pd species can transfer to the Au species without forming very stable structures (Fig. 2d), whereas the 1a oxidative adduct via aryl spill-over to Au species gives a slightly higher DG (Fig. 2e).{Considering the aforementioned indirect thioether metathesis on Pd complexes, 5 thiolate spillover onto the Au species probably promotes the transmetalation, enabling an efficient direct diaryl thioether metathesis with no additives (Scheme 1d).

Conclusions
In conclusion, we achieved the rst heterogeneously catalyzed direct C-S bond metathesis of diaryl thioethers with a wide substrate scope and functional group tolerance using Au 4.4 -Pd 1 / TiO 2 .Catalyst characterization and DFT calculations revealed the likely causes of the high catalytic activity of Au 4.4 -Pd 1 /TiO 2 : moderate adsorption energy of thioethers on the Au-Pd alloy nanoparticles (conferred by diluted Pd ensembles) and thiolate spillover onto Au species (which promotes subsequent transmetalation).These ndings are anticipated to guide the development of novel molecular transformations using multimetallic catalysts, especially by harnessing metal ensembles.
Scheme 1 Background (a)-(c) and (d) overview of the present study.

Table 1
Effect of catalysts on the metathesis of 1a and 1b a c Au 4.4 -Pd 1 /TiO 2 21 84 77