A novel strategy for stabilization of sub-nanometric Pd colloids on kryptofix functionalized MCM-41: nanoengineered material for Stille coupling transformation

The stabilization of sub-nanometric metal particles (< 1 nm) with suitable distribution remained challenging in the catalytic arena. Herein, an intelligent strategy was described to anchoring and stabilizing sub-nanometric Pd colloids with an average size of 0.88 nm onto Kryptofix 23 functionalized MCM-41. Then, the catalytic activity of Pd@Kryf/MCM-41 was developed in Stille coupling reaction with a turnover frequency (TOF) value of 247 h−1. The findings demonstrate that porous MCM-41 structure and high-affinity Kryptofix 23 ligand toward adsorption of Pd colloids has a vital role in stabilizing the sub-nanometric particles and subsequent catalytic activity. Overall, these results suggest that Pd@Kryf/MCM-41 is a greener, more suitable option for large-scale applications and provides new insights into the stabilization of sub-nanometric metal particles.

Preparation of Pd@Kryf/MCM-41. The colloidal Pd NPs was synthesized by using the impregnation reduction method according to our previous report with some modification 19 . First, 0.02 g Pd (OAc) 2 (Pd: 47.5%) and 0.2 g polyvinyl alcohol PVA was dispersed in 15 mL MeOH under sonication for 30 min. Subsequently, 5.0 mL 0.1 M of NaBH 4 was poured into the mixture mentioned above to fabricate a colloidal Pd solution. After stirring for 60 min under ambient conditions, 1.0 g Kryf/MCM-41 was added to the mixture. After stirring for 4 h at ambient conditions, the final solid result was collected by filtration and washed with EtOH several times then dried at room temperature. Wt% of Pd in the Kryf/MCM-41 mesoporous was calculated via inductively coupled plasma optical emission spectrometry (ICP-OES), and the resultant yield indicated 0.72%.
General procedure for Stille coupling reactions. In the model reaction, the mixture of aryl halides (3 mmol), triphenyltin chloride (1 mmol), Na 2 CO 3 (3 mmol), polyethylene glycol-400 (PEG-400, 2 mL) was added to 0.36 mol% Pd@Kryf/MCM-41 catalyst. The reaction vessel was capped and allowed to stir at room temperature for 3 h. After the reaction is complete, the organic phase was extracted with ethyl acetate/petroleum ether (1:2) and dried over sodium sulfate (Na 2 SO 4 ) to obtain the corresponding biphenyl. Finally, all biaryls were identified by 1 H and 13 C-NMR spectroscopy and comparison with the literature 28,40 .

Results and discussion
In addition to the scientific findings in introducing engineered nanomaterials [41][42][43][44][45][46] , herein, Pd@Kryf/MCM-41 mesoporous silica was presented for Stille coupling reaction (Fig. 1). Our initial efforts were geared towards preparing MCM-41 mesoporous silica material via the sol-gel method, which was followed by grafting Kryptofix (Fig. 2b). Furthermore, according to the Scherrer equation, the average crystalline size of Pd was found to be ~ 0.88 nm (Table S1, ESI), which demonstrated that sub-nanometric particles. Moreover, the formation of sub-nanometric Pd was confirmed further by and high-resolution TEM (HR-TEM) and STEM mapping microscopy. Subsequently, chemical groups of these meso-structures were studied by Fourier transform infrared (FT-IR) spectra (Fig. 2c). The peaks observed at 3430 cm −1 and 1627 cm −1 can be attributed to hydroxyl groups and adsorbed water 51 , respectively. The absorption band in 2931 cm −1 can be ascribed to the CH 2 -stretching vibration peak of Kryptofix 23 and the n-propyl aliphatic chain. Also, the peaks observed at 1411 cm −1 after the functionalization of MCM-41 with Kryptofix 23 confirms the covalent bonding crown ether ligand to the surface mesoporous silica.
TGA curves of MCM-41 and Pd@Kryf/MCM-41 demonstrate the weight loss of the organic material and thermal stability of Kryptofix 23 ligand in MCM-41. Figure 2f illustrates four weight loss steps in the TGA curve of Pd@Kryf/MCM-41 catalysts. The first weight loss (10.1%) between 30 and 140 °C is occurred due to the removal of adsorbed water moisture at the surface. The next weight loss (33.6%) from 140 to 295 °C is due to the decomposition of organic material and burning of ligand, which can be found that Kryptofix 23 material is relatively stable below 295 °C. After 295 °C, the phase remains completely changed, which was stable up to over 510 °C.
The interaction between Pd NPs with Kryf/MCM-41 was further investigated by XPS spectrum (Fig. 3). As for Kryf/MCM-41 meso-structure, the C 1s and N 1S XPS spectra in 285. 5    www.nature.com/scientificreports/ NPs with relatively bigger particle sizes were observed on the surface of MCM-41 (Fig. S1, ESI). A close inspection of HR-TEM image confirms the formation of NPs (Fig. 5e). Moreover, the statistical count of the particle size of Pd (> 100 counts and Gauss fit) in Kryf/MCM-41 surface was determined to be 0.88 ± 0.02 nm (Fig. 5f).
In addition to FESEM and TEM images, the STEM spectrum exhibit more detail about the deposition of Pd NPs onto the mesoporous material ( Fig. 6a-f). The dark-field STEM images of Pd@Kryf/MCM-41 can be affirmed that the Pd particles are homogeneously deposited onto the Kryf/MCM-41 mesoporous. Meanwhile, STEM mapping images and energy dispersive X-ray (EDX) analysis, confirm the presence of all constituent elements (i.e., Si, O, C, N, and Pd) in the mesoporous structure (Fig. 6g).
Catalytic activity of Pd@Kryf/MCM-41. The importance of the coupling reactions in pharmaceutical synthesis has led to broad interdisciplinary attention research 52,53 . On the other hand, the Stille coupling reaction due to harsh reaction conditions such as high temperature, inert atmosphere, and use of toxic solvents has caused a great challenge in the carbon-carbon coupling reactions. Therefore, after full identification of Pd@ Kryf/MCM-41, employing this nanostructure for the green synthesis of biaryls was paid attention (Fig. 7).
The experiments indicated that in the absence of Pd@Kryf/MCM-41 not afford the desired product (Table 1, entry 1). When the amount of Pd@Kryf/MCM-41 increased to 0.01 g (0.36 mol% Pd) in the presence of 1 equivalent Na 2 CO 3 , the yield production was also increased up to 66% (Table 1, entry 2). Therefore, by increasing the amount of Na 2 CO 3 to 3 equivalent, the yield was improved to 96% within 3 h, indicating a better conversion in comparison to the best catalyst systems (Table 3). However, different base was applied for the optimization such as N(Et) 3 , NaHCO 3 , CaCO 3 , NaOH, and Na 2 CO 3 . Among all the screened bases, it was observed that Na 2 CO 3 gave a higher conversion of biaryls. After screening different solvents in optimized conditions, PEG-400 as a green solvent turned out to give the best conversion. This solvent proved to have many applications in reaction such as oxidation 54 , reduction 55,56 , addition 57 , substitution 58 , coupling 17,59 , and etc. Also, solvents nonpolar like Toluene, n-Hexane, and dioxane were investigated and revealed slight conversion (  entries 15 and 16). When colloidal Pd NPs immobilize in Kryf/MCM-41 with particle size 0.88 nm demonstrate that they deliver the product with more than 96% yield whitin 3 h. Ultimately, by increasing the temperature reaction from ambient condition to 120 °C, a slight increase in the yield of the reaction was observed (Table 1, entry 17), indicating the mildness and convenience of operation.  Table 2). The excellent conversion was obtained for all the desired biaryls without over homocoupling. Also, aryl halides with electron-donating and electron-withdrawing groups are well coupled with triphenyltin chloride, which indicates the reaction is not sensitive to the electronic effects. Besides, aryl iodides were found to be most reactive in comparison with aryl bromides and aryl chlorides, which such results were anticipated due to the high bond energy of the lighter halides 60,61 . Furthermore, the sterically hindered aryl halides (entries 3, 5, and 10 Table 2) were good tolerated under the optimal reaction conditions. These results demonstrated that this reaction was not sensitive to both steric hindrance and electron efforts, which shows a promising potential for practical application.
In order to examine chemoselectivity, the reaction of 3-bromobenzaldehyde with triphenyltin chloride was investigated in optimize conditions (Fig. 8a). The analysis of the mixture reaction after 12 h demonstrates that www.nature.com/scientificreports/ biaryl product 3b in a yield of 93% and corresponding benzophenone derivative 3a was not observed. Moreover, chemoselectivity was further confirmed when 1-bromo-4-iodobenzene was employed as the reaction substrate (Fig. 8b). The reactions occurred exclusively with aryl iodides, but not aryl bromide and gave corresponding products 4a with excellent yields. Furthermore, to evaluate the scalability of this catalytic system, the reaction  www.nature.com/scientificreports/ was performed in 30 mmol scales, which conversion biphenyl in 91% (Fig. 8c). These findings indicate that the present protocol is a chemoselective, sustainable, and large-scale application. The catalytic activity of Pd@Kryf/MCM-41 was also compared with best catalyst systems reported in the literature ( Table 3). The proposed catalyst indicated an excellent catalytic activity than most of the reported works. It is evident that Pd particles in sub-nanometric scales reveal an excellent catalytic activity in terms of yield, reaction time, and catalyst load.
Proposed mechanism of Stille coupling reactions. To further develop the mechanism of action Pd NPs in coupling reactions, a plausible mechanism for Stille coupling using Pd@Kryf/MCM-41 was presented in Fig. 9a. The oxidative addition of aryl halides to Pd (0) Kryf/MCM-41 is the initial step to give complex Pd and intermediate II. After that, an organotin reagent reacts with intermediate II in transmetalation to afford intermediate III. Finally, reductive elimination of intermediate III gives biaryl product and Pd (0) Kryf/MCM-41. In the presence of Kryf ligand, PEG-400 as a solvent, and a base (Na 2 CO 3 ), probably the stable anionic complexes [Pd 0 @kryf] are formed, which can accelerate the oxidative addition of aryl halides with ph 3 SnCl 60 . Furthermore, X-ray photoelectron spectrum (XPS) analysis was used to identify the status of Pd in Pd@Kryf/MCM-41. After completing the Stille coupling reaction, the Pd 3d region exhibited two typical peaks centered at 336.98 and 342.38 eV, which can be ascribed to 3d 5/2 and 3d 3/2 states of Pd (0) respectively 69 (Fig. 9b).
Recyclability of the catalyst. The stability and reusability are key factors in practical application that must be considered for an effective catalytic system. To this end, the catalyst was separated by centrifuge after each use and prepared for the subsequent cycle. As shown in Fig. 10a, the activity was maintained for the first six times, suggesting that the catalyst was stable during coupling reaction. Furthermore, stable mesoporous silica material after the reuse was confirmed by FESEM (Fig. 10b) and TEM images (Fig. 10c-e). Besides, ICP-OES results indicate that after each cycle, the leaching of Pd is below 1.0 ppm (Table S2, ESI), which shows excellent physicochemical stability during Stille coupling reaction.

Conclusions
We indicated that Kryptofix 23 could be an excellent ligand for anchoring and stabilizing sub-nanometric Pd onto the pores of MCM-41. We also expanded an efficient protocol toward the economic synthesis of biaryls under sustainable conditions. This methodology revealed that the Pd@Kryf/MCM-41 has notable advantages such as excellent stability, negligible metal leaching, large scalability, and eco-friendly nature, which could coincide with     www.nature.com/scientificreports/ Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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