A low-nuclear Ag4 nanocluster as a customized catalyst for the cyclization of propargylamine with CO2

The preparation of 2-Oxazolidinones using CO2 offers opportunities for green chemistry, but multi-site activation is difficult for most catalysts. Here, A low-nuclear Ag4 catalytic system is successfully customized, which solves the simultaneous activation of acetylene (-C≡C) and amino (-NH-) and realizes the cyclization of propargylamine with CO2 under mild conditions. As expected, the Turnover Number (TON) and Turnover Frequency (TOF) values of the Ag4 nanocluster (NC) are higher than most of reported catalysts. The Ag4* NC intermediates are isolated and confirmed their structures by Electrospray ionization (ESI) and 1H Nuclear Magnetic Resonance (1H NMR). Additionally, the key role of multiple Ag atoms revealed the feasibility and importance of low-nuclear catalysts at the atomic level, confirming the reaction pathways that are inaccessible to the Ag single-atom catalyst and Ag2 NC. Importantly, the nanocomposite achieves multiple recoveries and gram scale product acquisition. These results provide guidance for the design of more efficient and targeted catalytic materials.

A low-nuclear Ag 4 nanocluster as a customized catalyst for the cyclization of propargylamine with CO 2 Lin Li 1,2,3,5 , Ying Lv 1,2,3,5 , Hongting Sheng 1,2,3 , Yonglei Du 1,2,3 , Haifeng Li 1,2,3 , Yapei Yun 2,3 , Ziyi Zhang 1,2,3 , Haizhu Yu 1,2,3 & Manzhou Zhu 1,2,3,4 The preparation of 2-Oxazolidinones using CO 2 offers opportunities for green chemistry, but multi-site activation is difficult for most catalysts.Here, A lownuclear Ag 4 catalytic system is successfully customized, which solves the simultaneous activation of acetylene (-C≡C) and amino (-NH-) and realizes the cyclization of propargylamine with CO 2 under mild conditions.As expected, the Turnover Number (TON) and Turnover Frequency (TOF) values of the Ag 4 nanocluster (NC) are higher than most of reported catalysts.The Ag 4 * NC intermediates are isolated and confirmed their structures by Electrospray ionization (ESI) and 1 H Nuclear Magnetic Resonance ( 1 H NMR). Additionally, the key role of multiple Ag atoms revealed the feasibility and importance of low-nuclear catalysts at the atomic level, confirming the reaction pathways that are inaccessible to the Ag single-atom catalyst and Ag 2 NC.Importantly, the nanocomposite achieves multiple recoveries and gram scale product acquisition.These results provide guidance for the design of more efficient and targeted catalytic materials.
The conversion of CO 2 into high-value-added chemicals [1][2][3][4][5][6][7] , such as starch 8 , carboxylic acid 9,10 , propylene carbonate 11,12 , and 2-oxazolidinone 13 , is considered a promising approach to achieve carbon neutrality and has become a hot topic in the field of catalysis.In particular, 2-oxazolidone compounds have important application potential in organic intermediates, antibacterial drugs and chiral auxiliaries 14,15 .Ideally, the greenest preparation of 2-oxazolone compounds is the cyclization of propargylamine with CO 2 .However, due to the unique structure of propargylamine, which contains both acetylene (-C≡C) and amino (-NH-) functional groups, it is difficult for most current catalysts to achieve this transformation [16][17][18][19] .Therefore, there is an urgent need to customize a catalyst with multiple active sites for the cyclization of propargylamine with CO 2 .
Single-atom catalysts (SACs) have been widely used for CO 2 conversion due to their high molar utilization, clear active site, and unique electronic structure [20][21][22][23] .However, the presence of only a single metal site inherently limits SACs performance [24][25][26][27][28] .In contrast, low-nuclear nanoclusters (NCs) not only show the same characteristics as SACs but also benefit from synergistic effects between adjacent metals [29][30][31][32][33][34][35][36] .However, low-nuclear-weight NCs are more prone to unpredictable structural transformations under harsh environments 37,38 , making it difficult to identify the true active component.Scott et al. reported that alkyne-protected Cu 20 NC do not require harsh pretreatment during catalysis 39 , Wang et al. reported that an alkyne-protected Au 38 NC exhibited superior performance compared to that of a sulfateprotected Au 38 NC 40 .Zheng et al. found that the activity of intact Au 34 Ag 28 (PhC≡C) 3 is significantly better than that of partially or completely removed ligands 41 .Alkyne ligands, as metal-organic ligands, are considered to play an important role in improving the catalytic performance [42][43][44] .
Therefore, we designed a low-nuclear Ag 4 NC protected by alkynes for the cyclization of propargylamine with CO 2 .As expected, the customized Ag 4 NC achieved the highest TON value of 5746.2, significantly higher than that of reported catalysts and the corresponding Ag 2 NC, Ag 6 NC and Ag 9 NC.Moreover, three Ag 4 *NC intermediates were captured and confirmed their structures by ESI and 1 H NMR. The key role of four Ag atoms revealed the feasibility and importance of low-nuclear catalysts at the atomic level.More importantly, the obtained Ag 4 /TNT nanocomposite afforded the product at the gram scale.

Result and discussion
A low-nuclear alkyne-protected Ag 4 NC and the corresponding Ag 6 NC and Ag 9 NC were synthesized according to the literatures [45][46][47] .All these Ag NCs were characterized by mass spectrometry, UV-vis absorption spectroscopy, and single-crystal diffraction analysis (Fig. 1a and Supplementary Figs.S1-S3), confirming the atomic monodispersity and the exact formula assigned to Ag 4 NC, Ag 6 NCand Ag 9 NC, respectively.N-Benzylprop-2-yn-1-amine (1a, HC≡CCH 2 NHBn) was selected as the preferred substrate for the cyclization of propargylamine to explore the catalytic performance of the customized Ag 4 NC.As expected, the Ag 4 NC protected by the acetylene ligand showed the best performance.To exclude the influence of the number of metal atoms, we designed and synthesized Ag 2 NC through a controlled experiment and compared their activity (Fig. 1a and Supplementary Fig. 4).Interestingly, among the Ag n (n = 2,4,6,9) NC series, Ag 4 NC had the highest catalytic activity with TON and TOF values up to 5746.2 and 2873.1 h −1 , respectively, which were higher than those of reported catalysts (Fig. 1b and Supplementary Table 3).Then, we investigated the catalytic activity of AgNO 3 , AgBF 4 and [Ag(C≡C t Bu)] n , and the results show that the activity of these catalysts is low.Furthermore, the Ag 4 NC with a Dppf (1,1'-Bis(diphenylphosphino)ferrocene) ligand was inactive for this reaction (Fig. 1b and Supplementary Table 1).The changes in the kinetics of the cyclization of N-benzylprop-2-yn-1-amine with CO 2 catalyzed by low-nuclear Ag 4 NC were monitored by in situ 1 H NMR (Supplementary Fig. 5a).Under the ideal conditions, we further explored the generality of the reaction for various propargylamine substrates.As shown in Fig. 1c and Supplementary Table 2, Ag 4 NC afforded the target products in high yields within 2 h for all propargylamine substrates (3a-4a) with alkyl terminations.Moreover, Ag 4 NC also reacted satisfactorily and afforded the corresponding products for substrates (5a-7a) with either electron-withdrawing or electron-donating groups.Most studies have reported that the low nucleophilicity of substrates such as N-phenylpropyl-2-yn-1-amine (2a) prevents the nucleophilic attack of carbon dioxide due to the benzene ring, resulting in a carbamate intermediate that is difficult to convert smoothly or requires high temperature conditions 16,48 .Much to our surprise and delight, the customized Ag 4 NC achieved highly active conversion of the N-phenylpropyl-2-yn-1-amine substrate at room temperature with yields up to 87%.
On this basis, we conducted relevant control experiments to gain more insight into the fundamental source of the catalytic activity of Ag 4 NC.The characteristic UV peak of Ag 4 NC showed a slight blueshift (8 nm) after Ag 4 NC was mixed with substrate 1a (1:2) for 1 h.In contrast, the characteristic peak of Ag 4 NC did not change at all within 2 h (Supplementary Fig. 5a).The adsorption of 1a on the Ag 4 NC was detected by Fourier Transform Infrared (FT-IR) Spectroscopy.As shown in Supplementary Fig. 5c, the dominant stretching peak of C≡C-H at 3290 cm −1 disappeared, and the peak of C≡C at 2106 cm −1 shifted to 2120 cm −1 .This reveals that the H atom of C≡C-H was removed from 1a and that the C≡C bond of 1a was activated by Ag 4 NC, which was related to the dehydrogenation activation of 1a 49 .To obtain direct evidence of the interaction between Ag 4 NC and 1a, we captured the Ag Meanwhile, the Ag 4 * (R 1 = species was also successfully identified in the reaction solution (Ag 4 + 4a + CO 2 ) (Fig. 2a and Supplementary Fig. 6b).
Consistent with the experimental observations, the ligand exchange of 3,3-dimethyl-1-butyne (BH) with N-benzylprop-2-yn-1amine (AH) was found to be thermodynamically feasible (exergonic by 6.4 kcal/mol, Fig. 3b).After that, two main types of mechanisms, depending on whether carboxylation occurs on the incoming A substrate (via ligand exchange, Path I) or an extra AH substrate (Path II, Supplementary Fig. 15 and Fig. 3b), were investigated.In path I, the coordinated A group on Ag 4 P 4 A 2 first reacted with DBU, and this step was slightly endergonic by 7.7 kcal/mol (Fig. 3b).Thereafter, carboxylation with CO 2 occurred on Ag Overall, the Ag 4 -catalyzed cycloaddition of N-benzylprop-2-yn-1-amine was highly exergonic by -37.7 kcal/mol, and the carboxylation step was the rate-determining step (Ag 4 P 4 A 2 -2 → Ag 4 P 4 A 2 c-1).Path II started with the coordination of an extra AH substrate, preferentially via an amino group, to form Ag 4 P 4 A 3 H-1 (Supplementary Figs. 15, 16 and Fig. 3b).Similar to the overall transformation in Path I, deprotonation, carboxylation, cyclization, and protonation then occurred to generate the final product.However, the overall energy demands for Path II were 4.4 kcal/mol higher than those for Path I (26.0 vs. 21.6 kcal/mol in Fig. 3b and Supplementary Fig. 15).Of note, in this study, some other pathways, including deprotonation and carboxylation on Ag 4 P 4 A 3 H-1, were also examined but were excluded because of their relatively high energy demands (Supplementary Fig. 17).In this context, Path I was the most feasible pathway.Moreover, the carboxylation process of path I was experimentally investigated by 13 C NMR and ESI-MS.As shown in Supplementary Fig. 19, the 13 C NMR carbon spectrum shows that the characteristic peaks of raw material 1a gradually weakened with the insertion of carbon dioxide.Meanwhile, new peaks assigned to the products gradually emerge and enhance.The characteristic peak signal changed significantly within 0.5 h, so we monitor the ESI-MS spectrum of the reaction solution during this period.To be noted, intermediate species IV (Fig. 3 ligand exchange).The tetranuclear Ag 4 core was pivotal in stabilizing the deprotonated amino group in Ag 4 P 4 A 2 -2 and the anionic carboxylic group in Ag 4 P 4 A 2 c-1.Such an interaction was unlikely in the Ag 2 system, as Ag-N coordination resulted in remarkable structural distortion in the diphosphine ligand.This was also the reason the yield of the Ag 2 system was significantly lower than that of the Ag 4 system (Supplementary Fig. 18).Based on the above, we proposed a mechanism for the cyclization of propargylamine with CO 2 catalyzed by Ag 4 NC (Fig. 3a).Obviously, Ag 4 NC first interacted with the propylamine substrate to produce the dehydrogenation activation product Ag 4 * NC, which remained in the form of Ag 4 * NC after cyclization.Throughout the catalytic process, activation of the substrate required coordination between multiple Ag atoms (the blue atoms represent the active Ag atoms), confirming the reaction pathways that are inaccessible to the Ag single-atom catalyst and Ag 2 NC.
To understand its applicability, the Ag 4 /TNT nanocomposite was successfully synthesized, which characterized by solid-state UV, XRD, TEM, XPS and element mapping (see Fig. 4 and Supplementary Figs.7-11 for details).The Ag 4 /TNT nanocomposites demonstrated the same activity as Ag 4 NC, while TNT carrier was inactive (Supplementary Fig. 12).In this scenario, a recycling experiment was performed with 1a as the substrate, and the reaction efficiency did not show significant changes even after five runs (Fig. 4d and Supplementary Fig. 13).To determine the practicability of this transformation, a scale-up experiment afforded 3-benzyl-5-methylene-2oxazolone in 1.2 g and >92% yield, which is comparable to previous results (Fig. 4e).
In summary, alkyne-protected low-nuclear Ag 4 nanocluster (NC) is designed to catalyze the cyclization of propargylamine with CO 2 .As expected, the low-nuclear Ag 4 NC achieves the highest TON value of 5746.2, significantly higher than that of reported catalysts and the corresponding Ag 2 NC, Ag 6 NC and Ag 9 NC.In addition, the Ag 4 NC successfully achieves the cyclization of propargylamine with CO 2 under mild conditions.In the elementary reaction of Ag 4 NC with substrates, including HC≡CCH 2 NHBn, HC≡CCH 2 NHCy and HC≡CCH 2 NH n Bu, we capture three Ag 4 * NC intermediates and confirm their structures by Electrospray ionization (ESI).Density functional theory (DFT) calculations further confirm the key role of four Ag atoms, revealing the feasibility and importance of low-nuclear catalysts at the atomic level.Importantly, the Ag 4 /TNT (functional titanate nanotubes) nanocomposite afford the product at the gram scale.Therefore, the customized Ag 4 catalyst improves the reaction activity while exerting the atomic economy similar to that of single atom catalyst, which has advantages in reducing cost.The present work provides a new perspective on the mechanism of the cyclization of propargylamine with CO 2 , which provides further support for the design of further atomic level catalysts and their efficient utilization.

Characterizations
The UV−vis.spectra were recorded on a Techcomp UV 1000 spectrophotometer.Transmission electron microscopy (TEM) was conducted on a JEM-2100 microscope with an accelerating voltage of 200 kV.The FT-IR spectra were recorded with a Bruker Tensor 27 instrument.The X-ray diffraction (XRD) patterns were obtained on Smart Lab 9 KW with Cu Kα radiation.The NCs loaded on the TNT catalyst support were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS).The X-ray photoelectron spectroscopy (XPS) measurements were conducted on ESCALAB 250Xi.Electrospray ionization mass spectra (ESI-MS) were recorded using a Waters UPLC H-class/Xevo G2-XS Qtof mass spectromete.

Catalytic activity
A typical "the cyclization of propargylamine with CO 2 " reaction was used to evaluate the catalytic performance of Ag 4 NC.Ag 4 NC (0.4 mg, 0.2×10 −3 mmol), propargylamines (0.5 mmol), and 1,8-Diazabicyclo [5.4.0] undec-7-ene(DBU) (0.05 mmol) were added to acetonitrile (1 mL) in the reaction tube.The reaction stirring for 2 h at 25 °C with the balloon in Carbon dioxide atmosphere.After the reaction stopped, The reaction solution was diluted by dichloromethane, The conversion and selectivity were determined by GC analysis and column chromatography (EtOAc/PE = 1:5).

Data availability
Data supporting the findings of this work are available within the article and its Supplementary Information.The data that support the findings of this study are available from the corresponding author upon request.The X-ray crystallographic structures reported in this work have been deposited at the Cambridge Crystallographic Data Center (CCDC) under deposition numbers 2254886 for [Ag 2 dppf 3 ].These data can be obtained free of charge from the CCDC via https:// www.ccdc.cam.ac.uk/structures/.

Fig. 2 |
Fig. 2 | Characterization of Ag 4 NC and Ag 4 * NC. a ESI-MS spectra of the intermediate Ag 4 * NC and simulation of the corresponding mass spectrum.b 1 H NMR spectra of 4a, Ag 4 * NC R 1 = cyclohexyl, Ag 4 NC, and Dppf.* in red (Characteristic hydrogen of Dppf) ※ in purple (Characteristic hydrogen of the methylene group of N-2-Propyn-1-ylcyclohexanamine) ⁑ in orange (The methyl hydrogen peak (1.11 ppm) of the C≡C t Bu ligand disappears.)c 31 P NMR spectra of Ag 4 * NC R 1 = cyclohexyl, Ag 4 NC, and Dppf.
4 P 4 A 2 -2 to generate the intermediate Ag 4 P 4 A 2 c-1 (c represents CO 2 ), with a low activation barrier of 12.1 kcal/ mol owing to the high nucleophilicity of the deprotonated amino group.Subsequent cyclization then occurred with a barrier of 16.3 kcal/mol.The resulting intermediate Ag 4 P 4 A 2 c-2 then underwent protonation and ligand exchange to complete the catalytic cycle.