Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome and (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a-h), and hydrazine monohydrate (NH2NH2•H2O) for the regioselective preparation of some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a-h). After synthesis and characterization of the mentioned cinnolines (3a-h), the in silico multi-targeting inhibitory properties of these heterocyclic scaffolds have been investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2(G2019S), hGSK-3ß, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, and hDHODH, which have confirmed their functions and roles in the neurodegenerative diseases (NDs), based on molecular docking studies, and the obtained results were compared with a wide range of approved drugs and well-known (with IC50, EC50, etc.) compounds. In addition, in silico ADMET prediction analysis was performed to examine the prospective drug properties of the synthesized heterocyclic compounds (3a-h). The obtained results from the molecular docking studies and ADMET-related data demonstrated that these series of 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines (3a-h), especially hit ones, can really be turned into the potent core of new drugs for the treatment of neurodegenerative diseases (NDs), and/or due to the having some reactionable locations, they are able to have further organic reactions (such as cross-coupling reactions), and expansion of these compounds (for example, with using other types of aryl(or heteroaryl)glyoxal monohydrates) makes a new avenue for designing novel and efficient drugs for this purpose.

Immobilized nickel boride nanoparticles on magnetic functionalized multi-walled carbon nanotubes: a new nanocomposite for the efficient one-pot synthesis of 1,4-benzodiazepines.

In this study, a new magnetic nanocomposite consisting of Ni2B nanoparticles anchored on magnetic functionalized multi-walled carbon nanotubes (Fe3O4/f-MWCNT/Ni2B) was synthesized and characterized using various techniques such as FT-IR, XRD, FESEM, SEM-based EDX, SEM-based elemental mapping, HRTEM, DLS, SAED, XPS, BET, TGA, and VSM. The as-prepared magnetic nanocomposite was successfully employed for the preparation of bioactive 1,4-benzodiazepines from the three-component reaction of o-phenylenediamine (1), dimedone (2), and different aldehydes (3), in polyethylene glycol 400 (PEG-400) as a solvent at 60 °C. The obtained results demonstrated that the current one-pot three-component protocol offers many advantages, such as good-to-excellent yields within acceptable reaction times, favorable TONs and TOFs, eco-friendliness of the procedure, easy preparation of the nanocomposite, mild reaction conditions, a broad range of products, excellent catalytic activity, green solvent, and reusability of the nanocomposite.

Green and efficient one-pot three-component synthesis of novel drug-like furo[2,3-d]pyrimidines as potential active site inhibitors and putative allosteric hotspots modulators of both SARS-CoV-2 MPro and PLPro.

In this paper, an environmentally benign, convenient, and efficient one-pot three-component reaction has been developed for the regioselective synthesis of novel 5-aroyl(or heteroaroyl)-6-(alkylamino)-1,3-dimethylfuro[2,3-d]pyrimidine-2,4(1H,3H)-diones (4a‒n) through the sequential condensation of aryl(or heteroaryl)glyoxal monohydrates (1a‒g), 1,3-dimethylbarbituric acid (2), and alkyl(viz. cyclohexyl or tert-butyl)isocyanides (3a or 3b) catalyzed by ultra-low loading ZrOCl2•8H2O (just 2 mol%) in water at 50 ˚C. After synthesis and characterization of the mentioned furo[2,3-d]pyrimidines (4a‒n), their multi-targeting inhibitory properties were investigated against the active site and putative allosteric hotspots of both SARS-CoV-2 main protease (MPro) and papain-like protease (PLPro) based on molecular docking studies and compare the attained results with various medicinal compounds which approximately in three past years were used, introduced, and or repurposed to fight against COVID-19. Furthermore, drug-likeness properties of the mentioned small heterocyclic frameworks (4a‒n) have been explored using in silico ADMET analyses. Interestingly, the molecular docking studies and ADMET-related data revealed that the novel series of furo[2,3-d]pyrimidines (4a‒n), especially 5-(3,4-methylendioxybenzoyl)-6-(cyclohexylamino)-1,3-dimethylfuro[2,3-d]pyrimidine-2,4(1H,3H)-dione (4g) as hit one is potential COVID-19 drug candidate, can subject to further in vitro and in vivo studies. It is worthwhile to note that the protein-ligand-type molecular docking studies on the human body temperature-dependent MPro protein that surprisingly contains zincII (ZnII) ion between His41/Cys145 catalytic dyad in the active site, which undoubtedly can make new plans for designing novel SARS-CoV-2 MPro inhibitors, is performed for the first time in this paper, to the best of our knowledge.

NiII NPs entrapped within a matrix of l-glutamic acid cross-linked chitosan supported on magnetic carboxylic acid-functionalized multi-walled carbon nanotube: a new and efficient multi-task catalytic system for the green one-pot synthesis of diverse heterocyclic frameworks.

In the present study, a new l-glutamic acid cross-linked chitosan supported on magnetic carboxylic acid-functionalized multi-walled carbon nanotube (Fe3O4/f-MWCNT-CS-Glu) nanocomposite was prepared through a convenient one-pot multi-component sequential strategy. Then, nickelII nanoparticles (NiII NPs) were entrapped within a matrix of the mentioned nanocomposite. Afterward, the structure of the as-prepared Fe3O4/f-MWCNT-CS-Glu/NiII nanosystem was elucidated by various techniques, including FT-IR, PXRD, SEM, TEM, SEM-based EDX and elemental mapping, ICP-OES, TGA/DTA, and VSM. In the next part of this research, the catalytic applications of the mentioned nickelII-containing magnetic nanocomposite were assessed upon green one-pot synthesis of diverse heterocyclic frameworks, including bis-coumarins (3a-n), 2-aryl(or heteroaryl)-2,3-dihydroquinazolin-4(1H)-ones (5a-r), 9-aryl-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-diones (7a-n), and 2-amino-4-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitriles (9a-n). The good-to-excellent yields of the desired products, satisfactory reaction rates, use of water solvent or solvent-free reaction medium, acceptable turnover numbers (TONs) and turnover frequencies (TOFs), along with comfortable recoverability and satisfying reusability of the as-prepared nanocatalyst for at least eight successive runs, and also easy work-up and purification procedures are some of the advantages of the current synthetic protocols.

A uniformly anchored zirconocene complex on magnetic reduced graphene oxide (rGO@Fe3O4/ZrCp2Cl x (x = 0, 1, 2)) as a novel and reusable nanocatalyst for synthesis of N-arylacetamides and reductive-acetylation of nitroarenes.

In this study, a crafted zirconocene complex on rGO@Fe3O4 as a novel magnetic nanocatalyst was synthesized and then characterized using FT-IR, SEM, EDX, VSM, ICP-OES, TGA, BET and MS analyses. Next, catalytic activity of the prepared nanocomposite rGO@Fe3O4/ZrCp2Cl x (x = 0, 1, 2) towards successful reduction of aromatic nitro compounds to arylamines using N2H4·H2O (80%) was investigated. The examined nanocatalyst also showed perfect catalytic activity for reductive-acetylation of aromatic nitro compounds to the corresponding N-arylacetamides without isolation of the prepared in situ amines using the N2H4·H2O/Ac2O system. Furthermore, acetylation of the commercially available arylamines to the corresponding N-arylacetamides was carried out by acetic anhydride in the presence of the rGO@Fe3O4/ZrCp2Cl x (x = 0, 1, 2) nanocomposite. All reactions were carried out in refluxing EtOH as a green solvent to afford the products in high yields. The obtained results exhibited that the nanocomposite of rGO@Fe3O4/ZrCp2Cl x (x = 0, 1, 2) showed a great catalytic activity in comparison to rGO and rGO@Fe3O4 as the parent constituents. Recovery and reusability of rGO@Fe3O4/ZrCp2Cl x (x = 0, 1, 2) were also examined for 8 consecutive cycles without significant loss of the catalytic activity. This establishes the sustainable anchoring of the zirconocene complex on the surface and mesopores of the rGO@Fe3O4 nanohybrid system.

Diverse and efficient catalytic applications of new cockscomb flower-like Fe3O4@SiO2@KCC-1@MPTMS@CuII mesoporous nanocomposite in the environmentally benign reduction and reductive acetylation of nitroarenes and one-pot synthesis of some coumarin compounds.

In this research, Fe3O4@SiO2@KCC-1@MPTMS@CuII as a new cockscomb flower-like mesoporous nanocomposite was prepared and characterized by various techniques including Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), SEM-based energy-dispersive X-ray (EDX) spectroscopy, inductively coupled plasma-optical emission spectrometry (ICP-OES), thermogravimetric analysis/differential thermal analysis (TGA/DTA), vibrating sample magnetometry (VSM), UV-Vis spectroscopy, and Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH) analyses. The as-prepared Fe3O4@SiO2@KCC-1@MPTMS@CuII mesoporous nanocomposite exhibited satisfactory catalytic activity in the reduction and reductive acetylation of nitroarenes in a water medium and solvent-free one-pot synthesis of some coumarin compounds including 3,3'-(arylmethylene)bis(4-hydroxy-2H-chromen-2-ones) (namely, bis-coumarins) (3a-n) and 2-amino-4-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitriles (6a-n) along with acceptable turnover numbers (TONs) and turnover frequencies (TOFs). Furthermore, the mentioned CuII-containing mesoporous nanocatalyst was conveniently recovered by a magnet from reaction environments and reused for at least seven cycles without any significant loss in activity, which confirms its good stability.

Reduction of 4-nitrophenol by a disused adsorbent: EDA-functionalized magnetic cellulose nanocomposite after the removal of Cu2.

In this paper, the fabrication of magnetically separable organic-inorganic hybrid nanoadsorbent via the functionalization of Fe3O4@SiO2@Cellulose with glycidyl methacrylate (GMA) and then ethylenediamine (EDA) was studied. The obtained nanocomposite system was characterized using FT-IR, XRD, SEM, EDX and VSM analyses. The EDA-functionalized magnetic cellulose exhibited a perfect capability towards removal of Cu2+ as well as Pb2+, Cd2+, Zn2+ and Ni2+ ions from the aqueous solutions. In addition, the influence of pH, contact time and initial concentration of Cu2+ were also investigated on capacity of the new designed cellulose absorbent. The examinations resulted that the adsorption process of Cu2+ is obeyed from the pseudo-second order kinetic model and the Langmuir isotherm. The maximum adsorption capacity of Cu2+ ions on the nanomagnetic cellulose was 81.67 mg/g. The magnetic cellulose after removal of Cu2+ ions was successfully applied as an efficient catalyst system for reduction of 4-nitrophenol to 4-aminophenol with excess amounts of NaBH4 in water.

Immobilized antimony species on magnetite: a novel and highly efficient magnetically reusable nanocatalyst for direct and gram-scale reductive-coupling of nitroarenes to azoarenes.

In this study, magnetic nanoparticles of Fe3O4@SbF x from the immobilization of SbF3 on magnetite were synthesized. The prepared nanocomposite system was then characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, vibrating sample magnetometry and inductively coupled plasma optical emission spectroscopy. Next, the catalytic activity of Fe3O4@SbF x MNPs was highlighted by one-pot reductive-coupling of aromatic nitro compounds to the corresponding azoarene materials with NaBH4. The reactions were carried out in refluxing EtOH within 6-25 min to afford the products in high yields. The reusability of the Sb-magnetite system was also studied for 6 consecutive cycles without significant loss of catalytic activity. This synthetic protocol provided several advantages in terms of introducing a novel catalytic system based on antimony species for direct and gram-scale preparation of azoarenes from nitroarenes, low loading of the nanocatalyst, mild reaction conditions, using ethanol as a green and economic solvent and high yield of the products.

Sulfonyl-bridged (copper-immobilized nickel ferrite) with activated montmorillonite, [(NiFe2O4@Cu)SO2(MMT)]: a new class of magnetically separable clay nanocomposite systems towards Hantzsch synthesis of coumarin-based 1,4-dihydropyridines.

In this study, the synthesis of a new class of magnetic clay-based nanocomposites by bridging of sulfonyl groups between copper-immobilized nickel ferrite (NiFe2O4@Cu) and activated montmorillonite is described. Synthesis of the clay nanocatalyst was carried out via the activation of montmorillonite by ClSO3H to afford sulfonated montmorillonite. The modified montmorillonite was then reacted with copper-layered nickel ferrite to afford the magnetic clay nanocomposite [(NiFe2O4@Cu)SO2(MMT)]. Next, the characterization of porous materials was carried out using scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller and vibrating sample magnetometer analyses. The obtained results showed that the clay nanocomposite containing a sulfonyl-bridge has a large surface area and magnetic properties versus the prepared one without the sulfonyl groups as (NiFe2O4@Cu)(MMT). The nanostructured clay had excellent catalytic activity towards the Hantzsch synthesis of coumarin-based 1,4-dihydropyridines via one-pot and three-component condensation of 4-hydroxycoumarin, aromatic aldehydes and ammonia. All reactions were carried out in water as a green and economic green solvent within 10-45 min to affords 1,4-DHPs in high to excellent yields. Reusability of the clay nanocomposite was investigated for six consecutive cycles without significant loss of catalytic activity. Based on this study, therefore, sulfonated montmorillonite could be considered an excellent support for the immobilization of magnetic materials.

Immobilized copper-layered nickel ferrite on acid-activated montmorillonite, [(NiFe2O4@Cu)(H+-Mont)], as a superior magnetic nanocatalyst for the green synthesis of xanthene derivatives.

In this study, the immobilization of copper-layered nickel ferrite on the surface and in the cavities of acid-activated montmorillonite (H+-Mont) was investigated. In this context, magnetic nanoparticles (MNPs) of NiFe2O4 as the prime magnetic cores were prepared. Next, through the reduction of Cu2+ ions with sodium borohydride, the nanoparticles of Cu0 were immobilized on the nanocore-surface of NiFe2O4, and the constituent NiFe2O4@Cu MNPs were obtained. Moreover, through the activation of montmorillonite K10 (Mont K10) with HCl (4 M) under controlled conditions, the H+-Mont constituent was prepared. The nanostructured NiFe2O4@Cu was then intercalated within the interlayers and on the external surface of the H+-Mont constituent to afford the novel magnetic nanocomposite (NiFe2O4@Cu)(H+-Mont). The prepared clay nanocomposite was characterized using FTIR spectroscopy, SEM, EDX, XRD, VSM and BET analyses. The obtained results showed that through acid-activation, the stacked-sheet structure of Mont K10 was exfoliated to tiny segments, leading to a significant increase in the surface area and total pore volume of the H+-Mont constituent as compared to those of montmorillonite alone. SEM analysis also exhibited that the dispersion of NiFe2O4@Cu MNPs in the interlayers and on the external surface of acid-activated montmorillonite was carried out successfully, and the nanoparticle sizes were distributed in the range of 15-25 nm. The BET surface analysis also indicated that through the immobilization of NiFe2O4@Cu MNPs, the surface area and total pore volume of the H+-Mont system were decreased. The catalytic activity of (NiFe2O4@Cu)(H+-Mont) was further studied towards the synthesis of substituted 13-aryl-5H-dibenzo[b,i]xanthene-5,7,12,14(13H) tetraones 3(a-k) and 3,3,6,6-tetramethyl-9-aryl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H) diones 5(a-k)via the pseudo-one-pot three-component cyclocondensation of 2-hydroxy-1,4-naphthoquinone (Lawsone)/dimedone and aromatic aldehydes in a mixture of H2O-EtOH (1 : 1 mL) as a green solvent at 80-90 °C. The (NiFe2O4@Cu)(H+-Mont) MNPs can be easily separated from the reaction mixture by an external magnetic field and reused for seven consecutive cycles without significant loss of catalytic activity.

Synthesis and Characterization of Copper (II) and Nickel (II) Immobilized on Silica- Coated Copper Ferrite: As Novel Magnetically Reusable Nano Catalysts Towards Reduction of Nitroarenes with NaBH4.

AIM AND OBJECTIVE: Nowadays, the design, synthesis and application of magnetically nanocomposite systems have attracted the attention of numerous scientists. The huge surface area and magnetic characteristic of nanoparticles as well as the inherent potentiality of the used metal species, makes them susceptible to have different reactivity in chemical reactions. In this context, we therefore encouraged to prepare a new design of magnetic nanocatalysts as CuFe2O4@SiO2@AAPTMS@Ni(II) and CuFe2O4@SiO2@AAPTMS@Cu(II) followed by monitoring of their catalytic activities towards reduction of nitroarenes with NaBH4. MATERIALS AND METHODS: Magnetically nanoparticles of CuFe2 O4@SiO2@AAPTMS@Ni(II) and CuFe2O4@SiO2@AAPTMS@Cu(II) were prepared through a four-step procedure: i) preparation of CuFe2O4 MNPs, ii) coating of CuFe2O4 nucleus by silica-layer using tetraethyl orthosilicate (TEOS), iii) layering of CuFe2O4@SiO2 MNPs with [3-(2-aminoethylamino)propyl] trimethoxysilane (AAPTMS), and iv) the complexation of CuFe2O4@SiO2@AAPTMS MNPs with an aqueous solution of Ni(OAc)2·4H2O or Cu(OAc)2·H2O. RESULTS: The catalytic activity of CuFe2O4@SiO2@AAPTMS@Ni(II) and the Cu(II)-analogue towards reduction of nitroarenes with NaBH4 was studied. The examinations resulted that using a molar ratio of 1:2 for ArNO2 and NaBH4 in the presence of 20 mg of nanocomposites in H2O under reflux conditions reduces various aromatic nitro compounds to arylamines in high yields. CONCLUSION: The immobilization of Ni(II) and Cu(II) species on silica-layered CuFe2O4 was investigated. Magnetically nanoparticles of CuFe2O4@SiO2@AAPTMS@Ni(II) and the Cu(II)-analogue showed the perfect catalytic activity towards reduction of nitroarenes with NaBH4 in H2O. All reactions were carried out within 2- 15 min to afford aniline products in high yields.

The Immobilized Copper on Nickel Ferrite: A Magnetically Superior Nanocatalyst for Chemoselective and Knoevenagel Synthesis of Bisdimedones and 1,8-Dioxo-octahydroxanthenes under Solvent-Free Conditions.

AIM AND OBJECTIVE: Nowadays, bisdimedones and 1,8-dioxo-octahydroxanthenes are considered as biologically active materials. Due to this, the synthesis of the mentioned materials is the subject of more interest. Although most of the reported methods have their own merits, however, they generally require the use of expensive reagents, hazardous organic solvents, a tedious workup procedure and reduced recyclability of the applied catalyst system. Overcoming of the above mentioned drawbacks, therefore, encouraged us to investigate the capability of nanostructured NiFe2O4@Cu towards the synthesis of bisdimedones and 1,8- dioxo-octahydroxanthenes under green reaction conditions. MATERIALS AND METHODS: Nanoparticles of NiFe2O4@Cu were prepared via a two-step procedure including the preparation of NiFe2O4 by solid-state grinding of Ni(OAc)2·4H2O and Fe(NO3)3·9H2O in the presence of NaOH followed by the immobilization of Cu(0) on the surface of NiFe2O4 nucleus via hydrazine hydrate reduction of Cu(NO3)2·3H2O. RESULTS: After the synthesis of NiFe2O4@Cu, the catalytic activity of the Cu-nanocatalyst towards Knoevenagel reaction of aromatic aldehydes with dimedone under different reaction conditions was investigated. The examinations showed that using the molar equivalents of aromatic aldehydes (1 mmol) and dimedone (2 mmol) in the presence of 0.15 g NiFe2O4@Cu under solvent-free conditions chemoselectively afforded structurally different bisdimedone products at 60°C and 1,8-dioxo-octahydroxanthenes at 120°C. CONCLUSION: In this study, magnetically, nanoparticles of NiFe2O4@Cu were prepared and then characterized using different analyses. The catalytic activity of the prepared Cu-nanocatalyst was also studied towards solvent-free Knoevenagel condensation of aromatic aldehydes with dimedone. All the reactions were carried out within 15-240 min to afford bisdimedone and 1,8-dioxo-octahydroxanthene products in high yields.

Synthesis and characterization of NiFe2O4@Cu nanoparticles as a magnetically recoverable catalyst for reduction of nitroarenes to arylamines with NaBH4.

In this research, a simple and efficient method for synthesis of magnetically separable NiFe2O4@Cu nanocomposite under co-precipitation conditions was described. X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), atomic absorption spectroscopy (AAS), Brunauer-Emmett-Teller (BET) and vibrating sample magnetometer (VSM) analyses confirmed the construction of NiFe2O4@Cu nanoparticles. The prepared core-shell nanocomposite showed a satisfactory catalytic activity for NaBH4 reduction of nitroarenes to arylamines. All reactions were carried out in a mixture of H2O-EtOH (1.5:0.5mL) within 1-12min under reflux conditions. The Cu nanocatalyst can be easily separated by a magnet and reused seven consecutive runs with no obvious loss of activity.

Dithiocarbamate to modify magnetic graphene oxide nanocomposite (Fe3O4-GO): A new strategy for covalent enzyme (lipase) immobilization to fabrication a new nanobiocatalyst for enzymatic hydrolysis of PNPD.

Immobilization of lipase was successfully achieved on the surface of magnetically separable Fe3O4/graphene oxide (GO) via a post-modification. This post modification was achieved in alternation to glutaraldehyde post-modification. The activity of immobilized lipase had not a significant loss in the activity while on the other hand, it is simply extractable (by keeping its major activity) from reaction crude by a magnet. Each step of immobilization was carefully monitored by characterization and all were successfully proved. SEM, TEM, XRD, EDX, and FTIR were used to characterize the support and immobilization process.

One-pot reductive-acetylation of nitroarenes with NaBH4 catalyzed by separable core-shell Fe3O4@Cu(OH)x nanoparticles.

One-pot reductive-acetylation of nitroarenes to acetanilides was carried out efficiently with NaBH4 in the presence of magnetically separable core-shell Fe3O4@Cu(OH)x nanoparticles. All reactions were carried out in H2O followed by acetylation with acetic anhydride within 5-17min giving the N-arylacetamides in high to excellent yields. Reusability of the catalyst was examined 9 times without significant loss of its catalytic activity.

Exfoliated Pd decorated graphene oxide nanosheets (PdNP-GO/P123): Non-toxic, ligandless and recyclable in greener Hiyama cross-coupling reaction.

Graphene oxide nanosheets were applied as a support for Pd nanoparticles in Hiyama reaction of various aryl halides and triethoxyphenylsilane to generate biaryl derivatives in aqueous conditions. Addition of surfactant during the catalysis caused a significant increase in yields of products through well-exfoliation of PdNP-GO. Among various studied surfactants, P123 showed superior activity rather to other surfactants, SDS and CTAB. This heterogeneous catalytic system has attained the advantages of being non-toxic, available, recyclable, ligand-free, and compatible to reaction medium.