Recent Progress of Metal Nanoparticle Catalysts for C–C Bond Forming Reactions

Over the past few decades, the use of transition metal nanoparticles (NPs) in catalysis has attracted much attention and their use in C–C bond forming reactions constitutes one of their most important applications. A huge variety of metal NPs, which have showed high catalytic activity for C–C bond forming reactions, have been developed up to now. Many kinds of stabilizers, such as inorganic materials, magnetically recoverable materials, porous materials, organic–inorganic composites, carbon materials, polymers, and surfactants have been utilized to develop metal NPs catalysts. This review classified and outlined the categories of metal NPs by the type of support.


Introduction
The synthesis of new functional molecules and the development of new reactions are important fields at the core of synthetic organic chemistry. Among them, C-C bond formation is one of the most important reactions. Until now, numerous kinds of C-C bond forming reactions, including regioselective reactions, stereoselective reactions, and cross-coupling reactions such as Suzuki-Miyaura, Mizoroki-Heck, Stille, Hiyama, Ullmann, and Sonogashira coupling reactions, have been developed and applied to synthesize many kinds of functional molecules such as drugs, natural products, optical devices, and industrially important starting materials. Homogeneous transition metal catalysts act in a pivotal role to achieve the above reactions, a huge kind of catalysts and ligands have been developed. However, homogeneous catalysts have a number of drawbacks, in particular, the lack of reuse of the catalyst. This leads to a loss of expensive metals and ligands and to impurities in the products. Although numerous kinds of heterogeneous catalysts have been developed in order to address these problems, heterogeneous catalysts are inferior to homogeneous catalysts at some points, such as in reactivity.
On the other hand, transition metal nanoparticles (NPs), which can be readily obtained by several methods, such as chemical reductions and thermal decompositions, are of great interest due to their high reactivity derived from their extremely small size and their large surface to volume ratio. Metal NPs have received much attention for their use in many promising catalytic and biomedical applications because they exhibit unique magnetic and catalytic properties that are not shown in bulk materials. The pioneering catalytic application of metal NPs was reported by Rampino and Nord in 1941 [1]. Since the pioneering works on C-C coupling reaction by metal NPs were reported by Reetz in 1996 [2,3], over the last few decades, the use of transition metal NPs in catalysis has expanded considerably and a huge variety of metal NP catalysts have been developed. Due to the enormous number of publications outlining metal NPs in recent years , this review will only focus on the metal NPs used as a catalyst for C-C bond forming reactions over the last five years. This review classified and outlined the categories of metal NPs by the type of support, such as inorganic materials, magnetically recoverable materials, porous materials, organic-inorganic composites, carbon materials, polymers and surfactants (Scheme 1). Scheme 1. Category of support.

Inorganic Materials
One of the most fundamental supports for metal NPs is inorganic materials such as metal oxides, clay, and so on [31][32][33]. There have been developed many highly active inorganic materials and supported metal NP catalysts, such as those which proceed the C-C bond forming reaction at room temperature [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Typical recent examples include the following: Trudell et al. reported a reliable method for the encapsulation of Pd NPs in halloysite, and the resultant Pd@halloysite catalyzed the Suzuki-Miyaura coupling reaction of aryl bromides at room temperature [52]. Verberckmoes et al. found that uncalcined, co-precipitated hydrotalcite-supported Pd NP catalysts are preferred above the calcined, impregnated ones when catalyzing basic promoted organic reactions. The reason for this is that the lack of calcination resulting in an ordered and porous hexagonal hydrotalcite structure causes a high accessibility of the active centers in combination with the high support basicity [53]. Pd NPs stabilized on magnesium oxide-carbon quantum dots catalyzed the Suzuki-Miyaura coupling reaction of aryl bromides and chlorides at room temperature. In addition, Pd loading and leaching in catalysts can be estimated by using fluorescence emission because a good relationship was observed between fluorescence intensity and the loading of Pd [54].
Miura and Shishido et al. developed one-pot synthesis of cyclohexene derivatives from the reductive cycloisomerization of diynes and subsequent [4+2] cycloaddition with dienophiles, based on the hypothesis that Pd species functioned as a redox site to form a palladacycle via the oxidative addition of two alkyne moieties (Scheme 2) [55]. They also found that the [2+2+2] cycloaddition of alkynes proceeded smoothly by PdAu alloy NPs while monometallic Pd and Au NPs were ineffective [56,57]. In the hydroalkoxycarbonylation of olefins using Ru NPs on CeO 2 , controlling the regioselectivities of linear esters and branched esters has been found to be related to the Ru size [58,59]. The Ru/Ceria catalyzed quinazolinones synthesis was also achieved by the same group (Scheme 3) [60].
Surface structure engineering has afforded many breakthroughs in enhancing the photocatalytic activity of titania. Among them, readily accessible urchin-like structures with properties of an interconnected porous framework and a high specific surface area and can increase the efficiency of light harvesting as well as facilitate the accessibility of reactants to the active sites [73]. InP/ZnS quantum dots were used as a sole photocatalyst to catalyze the C-C coupling reaction between 1-phenyl pyrrolidine and phenyl-trans-styryl sulfone without the aid of any cocatalyst or sacrificial oxidant or reductant [74]. The density functional theoretical (DFT) calculations of the adsorption energies of reaction intermediates leads to a design of the photocatalyst. Su et al. found the Cu NP-modified TiO 2 presented a high selectivity towards photocatalytic homocoupling of benzyl bromide into bibenzyl with a remarkable apparent quantum efficiency (AQE) of 15% by evaluation of the adsorption energies of benzyl radicals and bromine atoms on a series of selected metal surfaces (Scheme 5) [75]. Cu 2 O NPs supported on graphitic carbon nitride make a photoactive catalyst that has been developed for the preparation of ynone, aminoindolizines, and pyrrolo [1,2-a] quinoline. The electrons present in the conduction band under irradiation play an important role in enhancing the charge density of the Cu 2 O NPs, which strengthens the π-complex between Cu 2 O NPs and alkyne molecules, and acting as scavengers for the terminal hydrogen of alkyne to form the copper acetylide complex (Scheme 6) [76]. The size effect of Pt on the photocatalytic nonoxidative methane conversion efficiency was systematically investigated over x-Pt/Ga 2 O 3 with the particle size (x) ranging from 1.5 to 2.7 nm, where a volcano-shaped relation was observed [77]. The nature of the metal nanoparticle cocatalyst deposited on a TiO 2 photocatalyst dictated the product selectivity for the cross-coupling. The reaction of toluene with acetone gave 1-(o-tolyl)propan-2-one in the presence of Pd NPs, while Pt NPs promoted the crosscoupling reaction between the methyl group of toluene and acetone to afford 4-phenylbutan-2-one (Scheme 7) [78].

Magnetically Recoverable Materials
Metal NPs with a magnetic core can be easily separated from the reaction mixture by using an external magnet. Magnetic separation is an alternative to filtration or centrifugation as it prevents loss of catalyst and increases the reusability. This makes materials like Fe 3 O 4 a promising support for nanocatalysts. Magnetic nanoparticles have received considerable attention in terms of biocompatibility, thermal stability against degradation, large surface area, and low cost.
Li and Chen et al. confirmed that the number of acid sites within the zeolite frameworks were directly proportional to the catalytic activity of Pd NPs in Suzuki-Miyaura coupling reaction [152]. Gu and Zhang et al. have developed a novel covalent organic framework (COFs)-templated strategy for the size-controlled synthesis of stable and highly dispersed ultrafine metal NPs. With the aid of the evenly distributed thioether groups in the ordered framework structure, ultrafine metal NPs with a narrow size distribution were successfully obtained [153]. Arisawa et al. developed a well-established metal-nanoparticle catalyst preparative protocol by simultaneous in situ metal NPs and nanospace organization (PSSO). Several sulfur-modified Au-supported metal (Pd, Ni, Ru, and Fe) catalysts were constructed by self-assembled metal NPs, which were encapsulated in a sulfated p-xylene polymer matrix, and showed high catalytic activities for several C-C coupling reactions (Scheme 13) [154][155][156][157][158]. Scheme 13. One-pot synthesis of carbazole derivatives catalyzed by self-assembled multilayer Fe(0) NPs. Reproduced from [154], ACS: 2020.
El-Shall et al. found that ultra-small CuPd bimetallic nanoparticles deposited on a mesoporous-fumed silica support could be participated efficiently to the Suzuki-Miyaura coupling reaction of aryl bromides to give the corresponding coupling product within 30 min [159]. Bae, Byun, and Kim et al. prepared small and large Au NPs stabilized in mesoporous TiO 2 and poly(N-isopropylacrylamide) particles, respectively. These Au NPs exhibited a notably high catalytic activity in the homocoupling of phenylboronic acid, and interestingly, there was no obvious correlation between the apparent E a values and the size of Au NPs [160]. Dewan et al. reported the first synthesis of a renewable, recyclable, environmental benign bio-nanocellulose-based honeycomb-like heterogeneous surface from waste pomegranate peel. Pd NPs loaded onto the bio-nanocellulose is the effective catalyst for C-C coupling reaction to synthesize the potential bioactive biaryl/heterobiaryl and alkynyl/heteroalkynyl derivatives (Scheme 14) [161]. Xie et al. reported a one-step strategy for the design of size-selective heterogeneous catalysts, which was composed of microporous polymer carriers and ultrafine Pd NPs. This research will expand the application scope of microporous organic polymers in sizeselective heterogeneous catalysis (Scheme 15) [162]. Product selectivity is attributable to the size selectivity of micropores. Pt NPs encapsulated in H-BEA zeolite (Pt@H-BEA) catalyzed a one-step conversion of biomass-derived cyclopentanone to C10 cyclic hydrocarbons, i.e., bicyclopentane and decalin. While cyclopentane was produced with a yield of >70% on Pt@H-ZSM-5, which have the narrower pores (Scheme 16) [163]., Shi et al. achieved the selective synthesis of 3-methylindole from the reaction of aniline with glycerin using Cu NPs/SBA-15 modified with Al 2 O 3 , La 2 O 3 , and CoO. The characterizations revealed that the effect of Al 2 O 3 , La 2 O 3 , and CoO to enhance the polarity of the carrier, weaken the acidity, and to increase the number of weak acid centers, respectively (Scheme 17) [164].

Organic-Inorganic Composites
One of the most useful methods to obtain the inorganic materials with excellent properties as a support for metal NPs is functionalization of inorganic materials with organic molecules. On the other hand, metal-organic frameworks (MOFs), which includes a typical organic-inorganic composite, have attracted extensive attention as supports for metal NPs due to their huge surface area, large porosity, recyclability, and tunable functionality. Many kinds of metal NPs immobilized on the functionalized inorganic materials and MOFs have been reported until now .
Malta et al. synthesized the hydroxypropylated α-, β-, or γ-cyclodextrins-stabilized Pd NPs supported on ceria, and compared the reactivity in Suzuki-Miyaura coupling reactions. The catalysts based on βand γ-cyclodextrins-stabilized Pd NPs showed higher reactivities than α-cyclodextrins-stabilized Pd NPs, probably due to a higher degree of particles up to 5 nm [188]. A Suzuki-Miyaura coupling reaction took place smoothly at room temperature using thiourea-bridged periodic mesoporous organosilica and supported Pd NPs as a catalyst [189]. Ha et al. synthesized dual (temperature and pH)-responsive poly(N-isopropyl acrylamide-co-methacrylic acid) functionalized SBA-15. This material supported the fact that Pd NPs showed high catalytic activity for Suzuki-Miyaura coupling reactions at room temperature, while the activity decreased at higher temperature than LCST of PNIPAM [190]. It has been reported that Suzuki-Miyaura coupling reaction proceeded at room temperature using Pd NPs stabilized on CaAl-layered double hydroxide functionalized with tris(hydroxymethyl)aminomethane (Scheme 18) [191]. Scheme 18. The Suzuki-Miyaura cross-coupling reaction at room temperature catalyzed by LDH/Tris/Pd. Reproduced from [191], Elsevier: 2018.
Pd NPs stabilized on 12-tungstophosphoric acid modified zirconia catalyzed the Suzuki-Miyaura coupling reaction efficiently and TOF reached to ca.100000 h −1 [192]. Pd NPs decorated into a biguanidine modified-KIT-5 showed high catalytic activity for Suzuki-Miyaura coupling reaction under sonication at room temperature. The coupling product was obtained efficiently within 15 min [193]. Pd NPs immobilized on zirconium phosphate glycine diphosphonate nanosheets was confirmed to be an effective catalyst for Suzuki-Miyaura and Mizoroki-Heck reaction, and was applicable to the flow system [194]. Pd NPs supported on the hybrid nanomaterials based on thiol functionalized halloysite nanotubes and highly cross-linked imidazolium salts showed high performance in Suzuki-Miyaura and Mizoroki-Heck coupling reactions, and TOF of 3.88 × 10 6 h −1 was achieved in Suzuki-Miyaura coupling reaction [195]. Control synthesis of polyacrylamide brushes grafted onto silica particles (SiO 2 -g-PAAm), which can be used for the support of Pd NPs was achieved using reversible addition-fragmentation chain transfer (RAFT) polymerization. Appropriate activity and recyclability of SiO 2 -g-PAAm-Pd indicated in the Mizoroki-Heck coupling reaction of iodobenzene with n-butyl acrylate [196]. In Ullmann-type aryl iodides homocoupling, Au and Pd NPs loaded on ZIF-8 have been confirmed to be more efficient than the catalyst after calcination [197]. Kobayashi et al. developed poly(dimethyl)silaneimmobilized metal NPs with alumina as a second support, and the resulting catalysts have been utilized in several reactions (Schemes 19 and 20) [198,199]. Scheme 19. The carbonylative Suzuki-Miyaura coupling reactions catalyzed by polysilane/Al 2 O 3immobilized Pd NPs. Reproduced from [198], Thieme: 2021. Scheme 20. Asymmetric 1,4-addition of arylboronic acids to β,γ-unsaturated α-ketoesters. Reproduced from [199], Wiley-VCH: 2020.
A one-pot synthesis of benzo[c]pyrazolo[1,2-a]cinnoline-1-ones was achieved with Pd NPs dispersed on octakis[3-(3-aminopropyltriethoxysilane)propyl]octasilsesquioxane functionalized fibrous nanosilica (KCC-1) (Scheme 21) [200]. Thiocarbamide-functionalized graphene oxide-supported RhPd NPs have been tried for the Knoevenagel condensation of malononitrile and aryl aldehydes and showed an excellent catalytic activity to give the product within 35 min at room temperature (Scheme 22) [201]. Parida et al. reported that amino-functionalized Zr-based MOF (UiO-66-NH 2 ) was a suitable photocatalyst and support for metal NPs because it has a high surface area, tunable pores, and high thermal and chemical stabilities [202]. The same research group also investigated the utility of a graphene oxide/ZnCr-layered double hydroxide hybrid nanocomposite [203]. Chen and Wang et al. found that the porous coordination frameworks (PCFs) using the DIB-TETA as organic linkers and inorganic NPs as nodes exhibited superior photocatalytic performances in a noble metal-free Suzuki-Miyaura coupling reaction [204].

Carbon Materials
Charcoal is a classic commercial support for catalysts. Carbon materials have been proven to be suitable supports for heterogeneous catalysis, due to high thermal and chemical stability, their special electronic properties, and tunable textural properties such as surface area, porosity, and surface chemistry. To date, numerous kinds of metal NPs supported on carbon materials such as graphene and carbon nanotubes have been developed .
Ni@Pd core-shell NPs on carbon nanotubes (CNT) have been reported to show a high catalytic activity for carbonylative Suzuki-Miyaura cross-coupling reactions. The immobilization of the Ni@Pd NPs on CNT not only prevented their aggregation, but also significantly enhanced the accessibility of the catalytically active sites [232]. Hajipour and Farrokhpour et al. achieved the immobilization of Co NPs within a carbon nanotube channel, and found that Co NPs-in-CNTs, as compared to Co NPs-out-CNTs, exhibited excellent activity for Mizoroki-Heck reactions (Scheme 23) [233]. Chung et al. decorated Rh NPs on fullerene C60 to obtain a highly efficient nanocatalyst for Suzuki-Miyaura coupling reactions [234]. Chen and Li et al. designed an electron-deficient Au NPs-based catalyst via Schottky contact with boron-doped carbons for room temperature Stille coupling reaction. The electron-deficiency of Au NPs significantly increased the activation of C-Br bonds in alkylbromides and successive coupling reaction with allylstannanes [235]. Astruc et al. successfully immobilized α-Fe 2 O 3 nanocluster on graphene oxide (GO) by utilizing the supramolecular interaction between amphiphilic tris(triazolyl)-polyethylene glycol and GO. α-Fe 2 O 3 /GO worked well as a catalyst for Suzuki-Miyaura coupling reaction with only parts-per-million loading [236]. Taniike et al. revealed that a graphene oxide framework prepared with benzene 1,4-diboronic acid as a two-side linker was a superior support of Pd NPs to that with phenylboronic acid as a one side linker [237].
The coupling reaction of aryl chlorides can be achieved by using reduced graphene oxide-supported Pd NPs. The size of NPs and reactivity was dependent on the preparation temperature, and this catalyst was applied for the synthesis of key intermediates of important Sartans and Fluxapyroxad medicines (Scheme 24) [238]. Hoseini et al. utilized self-assembly at the toluene-water interface to produce a PdNiZn nanosheet and PdNiZn/reduced graphene oxide (rGO) ultrathin spherical NPs. The presence of rGO enhanced the catalytic activity, probably due to altering the electronic properties [239]. Ni NPs supported reduced graphene oxide, which has also been prepared by the hydrothermal process and investigated the catalytic activity for the homocoupling of arylboronic acids and alkynes [240]. Graphene acid is a convenient platform for the surface anchoring of Pd NPs with a narrow and sharp distribution. The size of NPs can be easily con-trolled by the amount of the Pd precursor, and the catalyst showed a high activity in the Suzuki-Miyaura coupling reaction and oxidative homocoupling of arylboronic acids under environmentally friendly conditions [241]. Three-dimensional graphene, which has excellent properties such as ultrahigh surface-to-volume ratio, high porosity, low density, etc., was used for the effective support of Au NPs and PdCo-bimetallic NPs [242,243]. C-methylations of alcohol, ketones, and indoles have been achieved using methanol and Pt/C as a sustainable C1 source and a catalyst, respectively. The reaction is driven by a borrowing-hydrogen mechanism (Scheme 25) [244]. Nitrogen-doped carbon-encapsulated Ni/Co NPs catalyzed pinacol couplings have been reported. The reaction mechanism is different to the classical pinacol coupling pathway, and the initial formation of silyl radicals is proposed (Scheme 26) [245]. Graphitic carbon nitride-supported Pd NPs (g-C 3 N 4 /Pd) is an efficient photocatalyst for Suzuki-Miyaura cross-coupling reactions. It has been confirmed that the reaction is driven by the light because the conversion of iodobenzene has the same trend as the absorption of light by the g-C 3 N 4 /Pd [246]. Dabiri et al. prepared AuPd alloy NPs immobilized on graphitic carbon nitride sheets, which enhanced Suzuki-Miyaura crosscoupling reactions at room temperature under visible-light irradiation. The photocatalytic activities strongly depend on the Au:Pd ratio of the alloy NPs. The activity of Au 1 Pd 1 /g-C 3 N 4 was much higher than that of the catalysts, compared with other Au:Pd ratios, probably because the electron transfer between the two metals occurs efficiently in the alloy NPs with an Au:Pd weight ratio near 1:1 (Scheme 27) [247]. Lim et al. investigated the role of the graphene interface in the photocatalyst, and found that the fast electron transfer was achieved in the presence of the reduced graphene oxide layer. Consequently, the highest catalytic activity for the visible-light induced C-C coupling reaction was obtained with Pd-nanodot-modified reduced GO-coated Au NPs [248].

Organic Polymers and Surfactants
Polymers such as poly(vinylpyrrolidone) (PVP) and surfactants including quaternary ammonium salt with a long alkyl chain are commonly used as stabilizers in the synthesis of metal NPs. For example, Rampino et al. used poly(vinyl alcohol) (PVA) to protect Pd and Pt NPs in 1941, and El-Sayed et al. initially reported the use of Pd nanoparticles stabilized by PVP as catalysts in the Suzuki-Miyaura coupling reaction of aryl iodides with arylboronic acids in aqueous media [1,249]. Dendrimers are also often utilized as the stabilizer for metal NPs, and pioneering studies were reported by Crook, Tomalia, and Esumi [250][251][252].
On the other hand, as a greener process, phytosynthesis that utilizes parts of whole plants to synthesize metal NPs is also under exploitation and is an advantageous and profitable approach [253]. Numerous kinds of metal NPs stabilized by organic compounds with a high molecular weight have been reported .
Peinemann et al. prepared Pd NPs with a subnanometer size (<1 nm) supported within the highly cross-linked network, which catalyzed Suzuki-Miyaura coupling reactions at a low temperature (<40 • C) [295]. Pd NPs stabilized by heteroatom donor-decorated polymer immobilized ionic liquid catalyzes the Suzuki-Miyaura coupling reaction of aryl bromides with remarkable efficacy in aqueous media under exceptionally mild conditions. Improvements in catalyst performance arising from the introduction of PEG are attributed to an increase in dispersibility and/or solubility, facilitating access to more exposed active sites [296]. The room temperature Suzuki-Miyaura coupling reactions have been confirmed in the presence of Pd NPs supported by polydopamine and Pd NPs synthesized using Sapindus mukorossi seed extract [297,298]. Studer et al. prepared Pd NPs by visible light irradiation to the DMF solution of silyl ketones and Pd(OAc) 2 . The diameter of Pd NPs could be adjusted to 1.9 to 5.2 nm depending on the photoinitiator used (Scheme 28) [299]. Pd NPs stabilized on poly(o-aminothiophenol) prepared by oxidation polymerization of o-aminothiophenol in the presence of Pd(NO 3 ) 2 showed a high catalytic activity for the Suzuki-Miyaura coupling reaction of aryl chloride in water [300]. The amphiphilic property of the eumelanin support helps Pd NPs to catalyze the Suzuki-Miyaura coupling reaction in water through a hydrophobic effect [301]. A series of Pd x M 147-x (M = Cu, Pt, Au, Rh, Ru) stabilized on poly(amidoamine) dendrimers were synthesized and their catalytic activities were investigated in Suzuki-Miyaura coupling reactions. Pd 74 Cu 73 DEN showed a similar activity to Pd 147 DEN and DFT calculations illustrated that the similar activity of the Pd 147 and Pd 74 Cu 73 DENs originate from the comparable energy barriers of the rate-determining steps [302]. Thang et al. developed the facile preparation method of polymer-metal nanocomposites for an improved catalytic performance by utilizing ultrasound as both the initiation and reducing source. Metal NPs were immobilized on the hydrophilic shell of the polymer matrix, and the size of the NPs were closely related to the ratio of tertiary amine groups in the polymer matrix to metal atoms [303]. Highly efficient Tsuji-Trost allylations in water have been achieved using Pd NPs stabilized by PVP. A very high TON of 537,000 was obtained in this system [304]. Yu et al. obtained the effective catalysts, which showed high activity for carbonylative Sonogashira coupling reactions by the introduction of salen moieties into highly cross-linked polyacrylamide [305]. Pd NPs were encapsulated within hybrid hydrogels made from an acylhydrazide-functionalized 1,3:2,4-dibenzylidene sorbitol (DBS-CONHNH 2 ) low-molecular-weight gelator combined with agarose polymer gelator via an in situ reduction of Pd(II). These heterogeneous gel-phase catalysts were successfully applied for several C-C coupling reactions (Scheme 29) [306][307][308]. Simple hydrophobic polymers without a coordination site such as polystyrene and poly(tetrafluoroethylene) have been confirmed to stabilize metal NPs and polymer-supported metal NPs were applicable to the recyclable catalyst for several reactions in water [309][310][311][312][313]. Scheme 29. Pd NPs@hybrid hydrogels catalyzed C-C coupling reactions. Reproduced from [307], Elsevier: 2020, and [308], RSC: 2018.
Oble and Rieger et al. synthesized a nanostructured well-defined core-shell nanogel with the ability to stabilize Pd NPs in its core by using reversible addition-fragmentation chain-transfer (RAFT)-mediated aqueous dispersion polymerization [314]. One of the most effective catalytic systems is micellar catalytic systems, which have been developed and expanded by Lipshutz and Handa groups. In their reaction systems, several reactions proceed at room temperature by designing an appropriate surfactant which form a micellar reaction field in water (Scheme 30) [315][316][317][318][319][320][321][322][323][324][325][326][327][328].  Bhalla et al. found that Supramolecular polymer of perylene bisimide derivative and ZnO NPs exhibited remarkable efficiency in direct dehydrogenative cross-coupling between terminal alkynes and aldehydes for the synthesis of ynones under visible light irradiation (Scheme 35) [338]. They also found that thiophene appended perylene bisimide derivative undergoes oxidative polymerization in the presence of gold ion to generate supramolecular polymeric ensemble, which showed photocatalytic activity in Mizoroki-Heck reaction [339].

Others
As seen, the pioneering works of Reetz and Jeffery [2,340], organic molecules and simple tetraalkylammonium salts are also able to be used as stabilizers for metal NPs [341]. The use of ionic liquids alone as NP stabilizers and reaction media for the Suzuki-Miyaura coupling reaction was also shown to be efficient [342]. The introduction of nitrogen-and phosphorus-based molecules is also of special interest, because they not only act as a stabilizer of metal NPs, but also as ligands, which enhance the catalytic activity of metal NPs. The metal NPs stabilized by small molecules were used not only as prepared ones, but also as in situ generated ones [343][344][345][346][347][348][349][350][351][352][353][354][355][356][357][358][359][360][361].
TPPTS (triphenylphosphine-3,3 ,3"-trisulfonic acid trisodium salt), which is one of the most well-known water-soluble phosphine ligands acted as not only as a stabilizer, but also as an activator for Pd NPs. Pd NPs/TPPTS catalyzed the Suzuki-Miyaura coupling reactions of aryl bromides at room temperature to afford the coupling product within 1 h [362]. In situ-generated Pd NPs by gallic acid was an extremely simple, green, and active catalyst, which catalyzed C-C coupling reactions at room temperature [363,364]. Kumar et al. developed a selective synthesis of Pd 9 Te 4 and PdTe, which are applicable for the catalyst in the Suzuki-Miyaura coupling reactions of aryl chloride [365]. By the same research group, a series of bidentate organochalcogen ligands (N, E; E = S/Se) were synthesized and they investigated the applicability for the support of Pd NPs [366,367]. Sewald et al. confirmed that solvent-stabilized Pd NPs were applicable for bio-orthogonal side-chain derivatizations of amino acids [368]. In situ-generated Pd NP-catalyzed threecomponent coupling of chloromethylarene with allyltrimethoxysilane and carbon dioxide (i.e., a carboxylative Hiyama coupling reaction) successfully produced α,β-unsaturated esters, whereas the coupling reaction with allytributylstannane (i.e., a carboxylative Stille coupling reaction) gave β,γ-unsaturated esters (Scheme 36) [369,370].  [373]. Wu et al. have established a cascade alkynylation and selective hydrogenation catalyzed by covalent binaphthyl-stabilized Pd NPs to provide a novel and highly efficient methodology for accessing Z and Z,Z-selective phosphinyl [3]dendralenes [374]. Binaphthylstabilized Pd NPs were also utilized to synthesize diphenylallylidenemethylindolin-2-ones, indanone derivative, 3-allylidene-2(3H)-oxindoles, and 3-allylidene-2(3H)-benzofuranones (Scheme 38) [375][376][377][378]. Obora et al. found that Ir NPs showed excellent catalytic activity in β-(aryl)methylation of alcohol [379,380]. Feng, Wang, and Bao et al. developed an efficient method for the selective synthesis of δ-lactone from the telomerization of 1,3-butadiene with CO 2 . This reaction was catalyzed by ultrasmall Pd NPs generated in situ [381]. Telmisartan-stabilized Cu NPs were utilized to synthesize naphtho[2,3-g]phthalazine derivatives as potential inhibitors of tyrosinase enzymes [382]. NPs in an oxidant/catalyst system. Ammonium peroxydisulfate (APS) was used as an initiator in these systems [383,384]. Ultrahigh molecular weight poly(methyl methacrylate) was synthesized using 2-bromoisobutyric acid ethyl ester (EBiB) in the presence of Pd NPs. The polymerization was initiated by the radicals produced from the reaction of EBiB with Pd NPs [385].

Conclusions and Perspective
C-C bond forming reactions have been widely utilized to synthesize many kinds of functional molecules such as biomaterials and natural products, fine chemicals, and medicines. On a small scale, these reactions are generally taken place with homogeneous catalysts utilizing the eminent advantages of high activity and selectivity. However, the homogeneous catalysts are not generally appropriate for industrialization because of their problems encountered in higher cost, stability, separation, and reusability. On the other hand, recyclable heterogeneous catalysts have some disadvantages, such as low activity and selectivity, the requirement of severe reaction conditions, and the leaching of metal species.
Metal NPs are expected to improve the above limits in industrialization. This review has outlined recent advances in metal NPs, which were used in the C-C bond forming reactions. Many types of support, such as inorganic materials, magnetically recoverable materials, porous materials, organic-inorganic composites, carbon materials, polymers and surfactants have been utilized to develop the metal NP catalysts. In each support, the excellent metal NPs which proceeded the C-C bond forming reactions, even at room temperature, or showed the photocatalytic activity, have been developed. In addition, most of them showed a high recyclability, and metal NP-catalyzed regio-and stereoselective reactions have been also developed. However, most of the reactions outlined in this review have been performed with catalysts at a mole percent loading (0.1 mol%-10 mol%). For industrial-scale applications, the use of an extremely low loading of catalysts is of great importance. For most catalysts (especially in the case of Pd NPs), the catalytic activity has been confirmed in well-known coupling reactions such as Suzuki-Miyaura, Mizoroki-Heck, Hiyama, Stille, Ullmann, and Sonogashira coupling reactions. In other words, new reactions catalyzed by metal NPs are not well developed. Considerable efforts over the last few decades have led to the development of metal NP catalysts which overcome various drawbacks such as reactivity and reusability. I hope that metal NPs will make a significant contribution to industry in the near future by further developments such as the metal NPs with a reactivity and selectivity that surpasses those of homogeneous catalysts, the new reaction peculiar to metal NPs, and the reaction systems with extremely low loadings of catalysts.