Human production and life are inseparable from chemical reactions, which are related to health, environment and energy^[1]. The development of catalytic technology makes it possible to achieve more accurate, efficient and controllable chemical reactions^[2]. Among them, transition metal catalysis has been widely used in the activation of various C-C/H bonds and C-heteroatom bonds^[3⇓⇓~6]. Palladium compounds are one of the most important transition metal catalysts in organic synthesis^[7⇓⇓~10]. In the homogeneous palladium catalyst system, the catalyst can be effectively dispersed in the reactant system and generally has high catalytic activity, but there is also a problem that the catalyst molecules are easy to polymerize, resulting in the reduction of the activity of the catalyst^[11]. The palladium catalyst used in the reaction is relatively expensive, and most of the efficient catalytic systems require carefully designed and synthesized ligand modification, which makes the cost of the catalyst higher. The catalyst is not easy to recycle, resulting in a waste of resources and metal residues in the system and products, which limits its wide application in the chemical industry, especially in the pharmaceutical field^[12].

In the past decade, the heterogeneous strategies of different homogeneous catalysts, such as loading, organometallic polymer, hypercrosslinking, self-loading, CTF and COF, have been widely and systematically studied^[13,14]. It is proved that the efficient and stable immobilization of homogeneous metal catalyst can realize the independent dispersion of catalyst molecules, effectively solve the problem of catalyst molecule polymerization, and also realize the recovery of catalyst, effectively solve the problems of cost and environmental hazards. And the dual optimization of the stability and the activity of the catalyst can be realized through the design of the catalyst structure. Immobilization is a strategy to achieve catalyst heterogeneity by immobilizing the dominant catalytic fragments on polymers, graphene, silica, zeolites, magnetic nanomaterials and other carriers through different linking methods (mainly chemical methods)^{[15][16][17,18]}.

Supported catalysts are also favored because of their simple synthesis and easy structural characterization. Among them, MNPs are widely used as carriers for the loading of palladium compound catalysts because of their nano-size, good dispersion of homogeneous catalytic system, high specific surface area for catalyst loading, and magnetic property for simple separation and recovery by external magnetic field. The reactivity and stability of MNPs @ L-Pd are not only related to the inherent characteristics of the support and the link between the active species and the support, but also closely related to the activity and stability of the dominant fragment of the catalytic center.

Therefore, in addition to selecting a suitable support, it is particularly important to design a dominant catalyst fragment with a suitable ligand that modulates the steric hindrance or electronic effect of the catalytic center.

In order to explore the construction strategy of a more efficient and stable catalytic system, based on the coordination characteristics of Pd atoms, researchers designed ligands to coordinate C, N, O, P and other elements as the main coordination atoms with palladium (Fig.Develop a series of MNPs @ L-Pd with different ligands (such as phosphine ligands, nitrogen-rich ligands, Schiff bases, palladacycles, nitrogen heterocyclic carbenes (NHCs), etc.) And bonding modes, and achieve efficient and recoverable catalysis for a variety of organic synthesis reactions. In this paper, the representative research progress in the past decade is reviewed, focusing on the activity and stability of catalysts with different ligand structures in organic reactions, and the prospects are put forward.

Sobhani et al. Synthesized MNP-supported NNN-Pd chelating catalyst MNP-21 through the synthetic route of Scheme 20 in 2015^[42]. Under the optimized conditions, MNP-21 can effectively catalyze the C-C coupling of different aryl halides with a broad substrate range, good functional group tolerance, and moderate to excellent yields. In the Heck coupling reaction of iodobenzene with n-butyl acrylate, MNP-21 could be recycled 10 times without any significant decrease in catalytic activity. The catalyst after 10 cycles was characterized by TEM, and no obvious aggregation of Pd was observed.

In recent years, Schiff bases, which are easy to synthesize and have high stability, have played a key role in coordination chemistry and catalysis as chelating multidentate ligands. Studies of Schiff base – transition metal complexes immobilized on various supports have been widely reported. Due to the high chemical stability and catalytic activity of tetradentate chelate coordination compounds, in 2014, Jaridi et al. And their colleagues successively synthesized superparamagnetic nanocatalysts MNP-22 and MNP-23 (Fig. 21 and 22) with average particle size of about 30 nm and 38 nm by loading Pd (II) Schiff base complexes on the surface of functionalized Fe₃O₄, and applied them to the C-C bond coupling reaction of aryl halides^[43][43,44]. When the loading of MNP-22 was 0.7 mol%, iodobenzene reacted with phenylacetylene at 90 ℃ for 0.5 H to give the target product in 94% yield. Secondly, in the Heck coupling reaction, only 0.3 mol% of MNP-23 was needed, and bromobenzene and n-butyl acrylate reacted at 110 ℃ for 3 H to obtain the coupling product in 90% yield. In the Suzuki coupling reaction of bromobenzene and phenylboronic acid, the product yield was 88% at 100 ℃ for 2. 5 H when the mole fraction of MNP-23 was 0. 3 mol%. In the corresponding reaction, MNP-22 and MNP-23 can be reused many times, while the catalytic activity remains basically unchanged, and the Pd leaching rate is negligible (Figure 21).

Sardarian et al. Synthesized MNPs supported Schiff base coordinated palladium polymer catalyst MNP-24 in 2019, with an average particle size of 30 nm^[45]. The catalyst has good catalytic activity for Heck coupling reaction and Sonogashira coupling reaction in the presence of aryl iodides. In the corresponding reaction, MNP-24 can be stably recycled for 8 times with good stability (Figure 23).

In May of the same year, Mahdavi et al. Prepared a new catalyst MNP-25 of (pyridine-2-methyl) dithiocarbamate (PDTC-Pd) complex supported on γ-Fe₂O₃@SiO₂, and investigated its catalytic performance in the Heck/Sonogashira coupling reaction of various aryl halides with various olefins/phenylacetylene in water^[46]. The catalyst showed the advantages of efficient recyclability, high turnover rate (TON) and high turnover frequency (TOF) even at low catalytic amount (5 mg, less than 0.1 mol%). There was no significant loss of activity in 10 consecutive runs of the Heck and Sonogashira reactions (Scheme 24).

Iron, nickel and their alloys are widely concerned as typical magnetic materials^[47]. In 2020, Sadeghzadeh et al. Prepared mesoporous silica-coated magnetic core-shell FeNi₃/DFNS MNPs with dendritic silica fiber morphology by hydrothermal method and microemulsion method, and supported Schiff base complex of Pd (II), and finally added melamine for heat treatment to synthesize Schiff base coordinated magnetic nanocatalyst MNP-26^[48]. The newly synthesized MNP-26 was applied to the preparation of cyclic carbonates from CO₂, which showed good catalytic activity and could be stably recycled for 10 times (Fig. 25).

In order to maximize the availability of metal catalysts and prevent the leaching of metal species, Rahman et al. Prepared catalyst MNP-27 by modifying the structure of phenanthroline Schiff base and successfully applied it to Suzuki-Miyara coupling^[49]. The catalyst showed good reactivity for both electron-deficient and electron-rich aromatic halides in the presence of a variety of organoboronic acids. MNP-27 can be simply recovered from the reaction system by using an external strong magnet and can be stably reused for 7 times, showing good catalytic activity and stability (Scheme 26).

Diethylenetriaminepentaacetic acid (DTPA) is widely used as a strong complexing agent for many metals because it contains three N atoms and four free carboxyl groups. If DTPA is bound to Fe₃O₄@SiO₂, palladium will be in the core position of three nitrogen atoms, while the overflowing Pd or Pd in solution can be captured again by the blocked four carboxyl groups, achieving efficient loading and stability of palladium. Li et al. First reported a DTPA-modified Fe₃O₄@SiO₂ magnetic nanoparticle-supported Pd nanocatalyst, MNP-28^[50]. With a high loading of Pd²⁺/Pd⁰ (0.535 mmol/G), the catalyst showed efficient catalytic activity for the Suzuki-Miyaura coupling reaction of aryl halides with phenylboronic acid, and could be stably reused for 20 times, showing great potential for industrial practical applications (Fig. 27).

N-heterocyclic carbene (NHC) -Pd complexes combine the catalytic activity of noble metals with the strong σ-electron donating ability, low toxicity, stability and easy modification of N-heterocyclic carbene, and become one of the most promising catalytic systems. In 2014, Esmaeilpou et al. Prepared bis-NHC palladium catalyst MNP-29 supported on poly (N-vinylpyrrolidone) grafted MNP^[51]. Under the optimal conditions, MNP-29 can effectively catalyze the Heck reaction of aryl halides with n-butyl acrylate or styrene, and the yield can reach 74% -98%; When the supported palladium nanoparticles were used for the Suzuki reaction of aryl halides with organoboronic acids, the yields were up to 77% – 97%. In Suzuki and Heck coupling reactions, the catalyst could be used continuously for 6 times without significant decrease in catalytic activity. In addition, ICP analysis confirmed that the stability of the catalytic system was good when the leaching amount of palladium was low after 6 cycles, 6% and 4%, respectively (Figure 28).

Although magnetic silica core-shell nanocatalysts are well dispersed in many solvents, most of the catalyst centers are hydrophobic environments, and when water is used as a solvent, a large amount of polyethylene glycol (PEG) and ionic liquid (IL) or n-Bu₄NBr(TBAB) are needed as solvents or phase transfer reagents. In 2015, Mahdavi et al. Reported a highly water dispersible/magnetically separable NHC-Pd catalyst MNP-30 based on PEG substituted imidazolium phosphite ionic liquid^[52]. In the aqueous Heck and Sonogashira coupling reactions, the catalytic activity of the catalyst was significantly improved, and a small amount (< 1 mg (0.0087 mol%)) of Pd catalyst was used to reduce 4-nitrophenol to 4-aminophenol. Under the template reaction condition, the Pd catalyst can be stably recycled for 10 times, and the leaching amount of Pd is less than 1 ppm. The unique water solubility and negligible Pd leaching rate indicate the high efficiency, versatility, environmental protection and economy of the catalyst (Fig. 29).

In 2016, Andr Andrés et al. Prepared catalysts MNP-31 and MNP-32 by grafting pre-synthesized single NHC-Pd complexes and double NHC-Pd complexes onto the surface of γ-Fe₂O₃@SiO₂, and compared their performance differences through Suzuki coupling reaction for the first time (Fig. 30)^[53]. The results showed that MNP-31 and MNP-32 had good catalytic activity and recycling rate compared with homogeneous Pd complexes without MNPs. Compared with MNP-31, MNP-32 has better stability, higher catalytic activity, mild reaction conditions, and even catalytic activity in the coupling of aryl chlorides with phenylboronic acid (MNP-31 can not catalyze well). In terms of recycling performance, both of them can be stably recycled for 12 times, and the leaching rate of palladium is very low (≤ 10 ppm).

In the same year, Singh et al. Designed and prepared a uniform magnetic nanoparticle-supported oxime complex catalyst MNP-33 (Fig. 31) with an average particle size in the range of 5.90 ~ 14.39 nm by anchoring carbon heterocycle on the surface of magnetic Fe₃O₄@SiO₂, and proved that it could effectively promote the Heck, Suzuki and Sonogashira coupling reactions of aryl iodides, with high reaction yield and stable recycling up to 7 times^[54]. Although the catalytic activity of MNP-33 is not outstanding, the stability of the catalyst is greatly improved due to the formation of Pd-C bond.

In 2017, Tu et al., for the first time, synthesized a novel molecular acenaphthylimidazole-type NHC-palladacycle complex catalyst MNP-34 with a well-defined structure through the strategy of enlarging the conjugated system of NHC^[55]. The catalyst has a uniform morphology, an average particle size of 150 nm (TEM), and good thermal stability (DSC-TGA), and can be stored in the environment for many years. MNP-34 exhibits unprecedented catalytic activity of heterogeneous palladium catalysts: efficient Suzuki-Miyaura coupling reactions of inert heteroaryl chlorides with various boronic acids were achieved to give the corresponding functional acridine derivatives at 0.5 mol% catalyst dosage. The catalyst can be stably recycled for 5 times without obvious activity loss. The leaching rate of Pd in the filtrate tested by ICP is negligible. According to TEM, the morphology of the catalyst before and after recovery does not change significantly. The sixth decrease in catalytic activity may be due to the poisoning of the catalyst by the substrate (Figure 32).

In 2017, Patil et al. Synthesized catalysts MNP-35 and MNP-36 and applied them to Suzuki coupling and Heck coupling reactions^[56,57]. The results showed that both MNP-35 and MNP-36 exhibited excellent catalytic activity for Suzuki coupling reaction of different substrates under mild conditions, with yields up to 95%. In the Suzuki cross-coupling reaction of bromobenzene and phenylboronic acid, MNP-36 could be recycled for 7 times without significant activity loss, and the product could still be obtained in a considerable yield of 81% even after 12 times of recycling. In contrast, MNP-35 could be recycled for 5 cycles, and a decrease in catalytic activity was observed when the sixth cycle was started. This may be due to the change of catalytic activity caused by the change of steric hindrance effect caused by the addition of nitro group on the phenyl ring in the N-ligand. At the same time, under the optimized conditions, in the Heck cross-coupling reaction of bromobenzene and styrene as a model reaction, there was no significant decrease in the activity of MNP-36 after five cycles. However, further recycling led to a decrease in the yield of the cross-coupled product, which was still 74% after 12 recycles. One of the reasons for the reduced recovery efficiency of the Heck cross-coupling compared with the Suzuki cross-coupling reaction may be the difference in the reaction conditions required for the two coupling reactions (Scheme 33).

In addition, vitamin B1 is a water-soluble vitamin and a degradable green thiazolyl nucleophilic heterocyclic carbon, which can be used as a biodegradable and non-toxic NHC ligand to replace the toxic and poorly biodegradable imidazolyl NHC ligand. In 2018, Rafiee et al. Synthesized catalyst MNP-37 by covalently linking thiamine hydrochloride (VB1) with Fe₃O₄@SiO₂ to form a biodegradable complex with palladium, and applied it to Suzuki coupling reaction^[58]. Under the optimal conditions, only 0. 001 G of catalyst (0. 022 mmol%, Pd) can effectively catalyze the coupling reaction of various aryl halides with substituted phenylboronic acids, and the corresponding products can be obtained in a short time with a yield of 98%. However, the catalytic system has low reactivity for -Cl-based aromatic substituents, and the catalyst can be recycled five times (Figure 34).

Pincer pyridine NHCs have attracted much attention because of their trinity rigid structure, which makes the metal complexes have high stability against air and moisture. Rafiee et al. Prepared a magnetic chitosan-supported Pd-CNC-type pincer complex catalyst (MNP-38) by grafting modified chitosan onto MNP, and applied it to Suzuki coupling reaction.Under the optimal conditions, the catalytic system can effectively catalyze the coupling reaction of various aryl halides and arylboronic acids, and the corresponding biphenyls can be obtained in high yields except for the coupling reaction involving aryl chlorides^[59]. The catalyst can be stably recycled for 13 times. In this pincer composite, the metal atom is more tightly bound to the ligand, which is particularly stable and durable compared to traditional pincer complexes containing heteroatoms in the side arm (Scheme 35).

In 2018, Sardarian et al. Reported theophylline-NHC-Pd (II) catalyst MNP-39 with Pd (II) coordination compound supported on MNPs, and used it in Suzuki and Sonogashira coupling reactions^[60]. MNP-39 was able to efficiently catalyze the Suzuki and Sonogashira cross-coupling reactions of various aryl halides with phenylboronic acids, terminal aromatics, and aliphatic alkynes in good yields. Compared with other supported catalysts, the reaction conditions are mild and the catalyst content is less (only 0.37 ~ 0.5 mol% under the optimal conditions). As a stable phosphine-free Pd catalyst, MNP-39 showed good stability, could be recovered by magnetic separation and repeated for 8 reaction cycles, no significant activity loss was observed, and the leaching rate of palladium was less than 0.18 ppm (Scheme 36).

In 2019, Tahmasbi et al. Formed magnetic MCM-41 nanoparticles by doping Fe₃O₄ nanoparticles functionalized by silica layer on the MCM-41 framework, and then immobilized the N-heterocyclic carbene-coordinated Pd (II) complex on the surface of magnetic MCM- 41 by APTES or CPTMS to prepare magnetic nanocatalysts MNP-40-A and B, respectively (Fig. 37)^[61][62]. It has been shown that the two catalysts are widely suitable for the coupling of various aryl halides (Suzuki reaction and Heck reaction). Under the optimized experimental conditions, the surface structure and morphology of catalyst MNP-40-a did not change when it was recycled, and it could be reused for 8 times with an average separation rate of 97.5%. In addition, the AAS results showed that the recycled catalyst MNP-40-B could be reused for 7 times, and the average separation rate could reach 93. 14%, and the activity of both was not reduced.

In addition, our group successfully prepared a core-shell structure of magnetic mesoporous nanoparticle-supported NHC-palladacycle catalyst MNP-41 in 2022, which exhibited broad substrate adaptability in Suzuki cross-coupling of arylboronic acids and arylhalides^[63]. Moreover, MNP-41 has high catalytic activity and reusability, and its catalytic performance does not decrease significantly even after 12 cycles (Figure 38).

The catalytic performance of heterogeneous catalysts is not only related to the inherent characteristics of the support and the link mode between the dominant catalyst and the support, but also closely related to the specific structure of the dominant catalyst fragment, that is, the coordination mode of the active species itself. In recent years, magnetic nanoparticles (MNPs) have become an attractive carrier due to their dual advantages of magnetic properties and nanosize effect. MNPs @ L-Pd has also attracted much attention because of its simple synthesis, easy structural characterization, easy separation, and high activity. MNPs @ L-Pd has not only been developed with rich support types and loading strategies, which has the advantages of easy in situ magnetic separation and recycling, but also designed a variety of superior catalyst fragments through the multidentate coordination of C, N, O, P, S, Se and other coordination atoms.It has high catalytic activity and stability in C-C bond formation reactions with aryl halides and heterocyclic halides as substrates, and even has certain catalytic activity and universality for aryl chlorides with low reactivity (Table 1-3), showing good catalytic activity and stability, and has certain industrial application prospects.

Although the development and application of MNPs @ L-Pd have made great progress in recent years, there are still many challenges. (1) According to the existing work progress and development trend in this field, it is not difficult to find that the magnetic nanocatalyst supported by organic palladium complex still has the defects of poor thermal stability, short service life of the catalyst, and is not conducive to continuous production. Therefore, the design of MNPs @ L-Pd catalysts with higher support stability and coordination stability is one of the goals pursued by researchers. (2) The existing catalytic system can catalyze a single type of reaction, and the catalytic amount in the reaction is high, the reaction temperature is not mild enough, the applicability of the substrate needs to be expanded, and the catalyst activity needs to be improved. It is urgent to develop diversified new catalytic materials with high loading and efficient catalytic activity through the careful design of supports and superior catalyst ligands. (3) There is also much room for research on the preparation process of MNPs supported palladium catalyst and its catalytic mechanism in the coupling reaction. (4) MNPs supported chiral catalysts have good application prospects in the field of asymmetric catalysis, but they are still in the initial stage and are worthy of further exploration. (5) With the development of organic technology, more and more practical needs have been put forward, and in the past few years, the combination of photocatalysis, electrocatalysis and organocatalysis has made remarkable progress in modern chemical synthesis^{[64⇓~66][67]}. At present, it has been proved that compared with heat source, the rational application of light and electricity can achieve catalysis under mild conditions, which is conducive to the recycling of catalysts^[68]. Therefore, the cross-domain synergistic catalysis of organometallic catalysts needs to be studied and expanded urgently.