Deep Eutectic Solvents for C–H Activation: Comparison
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Please note this is a comparison between Version 3 by Dean Liu and Version 2 by Dean Liu.

Green chemistry principles have underpinned the development of deep eutectic solvents (DESs). 

  • deep eutectic solvents
  • green chemistry
  • C–H activation
  • cross-coupling

1. Introduction

The use of solvents is a major concern in applying sustainable principles in the chemical industry. Solvents are widely used for various applications, such as coatings, paints, product synthesis, adhesives, equipment cleaning, and reaction media [1][2][3]. The selection of an appropriate solvent is crucial for a chemical process [4][5]. Traditionally, volatile organic derivatives have been used as the solvents, which are non-renewable, highly toxic, non-degradable, and accumulate in the atmosphere due to their low-boiling points, which contribute to a high-carbon footprint [6][7][8][9][10][11]. Recent reports have highlighted that solvents constitute 80–90% of the non-aqueous content in materials used for producing active pharmaceutical substances and fine chemicals [12]. Therefore, it is vital to discover substitute solvents to enhance the sustainability of these industries.
In this context, DESs (Deep Eutectic Solvents) have been proposed as alternative solvents in organic chemistry. They have emerged as a potential class of solvents for various organic chemistry applications. DESs are characterized as systems resulting from a eutectic mixture of two or more components, typically Lewis or Brønsted acids and bases, that encompass diverse anionic and/or cationic species [13]. The formation of DESs involves intermolecular interactions between their constituents, facilitated by various types of bonds, including but not limited to hydrogen bonding. These interactions result in a reduction of lattice energy, thereby contributing to the lowered melting point of DESs, as compared to their individual components [14]. Eutectic mixtures can be prepared by combining the constituent components in the correct proportions and then heating the mixture until it melts [15]. This method is highly efficient in terms of atom economy, with no by-products generated. Compared to similar ionic liquids, DESs offer advantages, such as easy preparation and high-atom economy. DESs also have other beneficial properties, such as low-boiling points, low-material costs, being sourced from renewable sources, having low toxicity, high biodegradability, and the potential to replace volatile organic compounds (VOCs) in organic reactions [16]. Therefore, DESs hold significant promise as a potential alternative to VOCs in organic reactions. They can be classified into five main types based on their composition:
  • ▪ Type I: composed of a metal chloride and a quaternary ammonium salt.
  • ▪ Type II: similar to type I, but with hydrated metal halides instead of non-hydrated ones.
  • ▪ Type III: composed of a hydrogen bond donor (HBD), such as alcohols, amino acids, or amides, and a quaternary ammonium salt.
  • ▪ Type IV: composed of a transition-metal salt and HBDs.
  • ▪ Type V: composed solely of non-ionic components.
C–H activation is a process that enables the direct functionalization of carbon–hydrogen bonds, without requiring pre-functionalization. On the other hand, cross-coupling reactions can join a wide range of organic molecules, including aryl halides, vinyl halides, aryl triflates, boronic acids or boronates, alkynes, and alkyl halides, to form a new molecule with a carbon–carbon bond. There are numerous publications, such as articles and reviews, that discuss C–H activation and cross-coupling reactions [17][18][19][20][21][22][23][24][25][26][27][28][29][30]. These reactions have been extensively studied and widely used in organic synthesis, making them a popular research topic in chemistry. While OVSs have been widely used as reaction media for this type of reaction, there has been growing interest in exploring the potential of DESs as a greener alternative. In catalytic transformations, it is crucial to ensure that the catalyst used is compatible with the DESs employed to produce the desired products with selectivity and efficiency. Sometimes, transition-metal salts can serve as the catalysts due to the high polarity of DESs.
One key property of DESs is their ability to activate electron rich substrates, including carbohydrates, amino acids, and enzymes. DESs often have an electron deficiency, which can be compensated for by the electron rich substrate. When the DES is brought into close proximity with the substrate, electrons can be transferred from the substrate to the DES. As a result, the substrate is activated through a process known as electron transfer activation. By activating substrates, DESs have improved catalytic activity, making them attractive for use in a variety of chemical reactions and processes [31]. One significant advantage of DESs over organic volatile compounds is their ability to recover the catalyst-solvent system, allowing for recyclability and increasing the sustainability of the process. researchers highlight recyclability by quantifying reaction cycles for each example. DESs surpass organic volatile compounds in dissolving reagents and substrates, making them excellent for cross-coupling and C–H activation reactions.

2. C–H Activation Reactions

In 2017, Punzi and coworkers reported, for the first time, the use of DESs in C–H activation reactions to prepare thiophene−aryl derivatives 3 [32]. Hydrophobic DESs worked better than hydrophilic ones, but they decided to choose the hydrophilic DES composed of choline chloride (ChCl) and urea, in a molar ratio of (1:2), as it had a simpler work-up process. In the presence of Pd2(dba)3 (5 mol%) as the catalyst, P(o-MeOPh)3 as the ligand, Cs2CO3 as the base and pivalic acid (PivOH) (1 equiv.) as additive, the diarylation of 5-octylthieno [3,4-c]pyrrole-4,6-dione (TPD) 1 with aryl iodides 2 successfully occurred, providing high yield of the desired product 3 (Scheme 1). No reaction took place in the absence of the ligand. Electron rich aryl iodides were more reactive than electron poor ones, yielding moderate to good yields. Bromobenzene exhibited less reactivity as a coupling partner, resulting in low yields. The optimized reaction conditions were used to prepare aromatic molecules for push-pull molecular and polymeric semiconductors.
Molecules 28 04651 sch001 550
Scheme 1. Thiophene−aryl coupling reaction via C–H bond activation in DES.
Heydari and co-workers described an environmentally safe approach for the arylation of imidazoles with aryl bromides in DESs [33]. Authors synthesized a palladium-based magnetic reduced graphene oxide (MRGO@DAP-AO-Pd(ll)) as a reusable catalyst for C-5 arylation of 1,2-dimethyl-1H-imidazole 4 with 4-bromobenzaldehyde 5. Various types of choline chloride based DESs were studied. The best solvent for the reaction system was K2CO3:glycerol (1:5) (Scheme 2). DES can also offer several advantages for this reaction. The high basicity of the solvent can promote the deprotonation of the imidazole compound, which can enhance its reactivity towards the palladium catalyst [34].
Molecules 28 04651 sch002 550
Scheme 2. The arylation of imidazoles via C–H bond activation.
Various electron rich and electron deficient aryl halides were used to investigate the limitations of the optimized conditions for the C5-arylation of 1,2-dimethyl-1H-imidazole. C5-arylated products 6 were obtained in good yields using 1-methyl-1H-imidazole with several (hetero)aryl bromides. C5 position of imidazole is more reactive than C2 and C4 position for monoarylation, with only traces of the C2-arylated product detected. The catalyst could be used for seven subsequent runs with a broad substrate scope without significant loss in activity within this protocol. Recently, Tran and Hang have described DES-catalyzed arylation of benzoxazoles 7 with aromatic aldehydes 8 (Scheme 3) [35]. When using ZnCl2:ethylene glycol (1:4) as both the catalyst and solvent, benzoxazoles can be combined with benzaldehyde derivatives to form C2-arylation products 9. Without exclusion of air, benzoxazoles and aromatic aldehydes, either with electron donating or electron withdrawing groups, yielded the desired products in high to excellent yields. High to excellent yields of the desired products were obtained at 120–140 °C for 4–6 h. In addition, benzothiazole and benzimidazole were compatible with aromatic aldehydes affording good yields of the desired products 9. Extraction with diethyl ether was performed once the reaction finished. As an interesting side note, DES ZnCl2:ethylene glycol (1:4) can be reused up to five times without significant loss in activity. Benzoxazoles arylation has been reported frequently in different solvents. These solvents include H2O/diglyme [36], PhCl [37], DMF [38], pivalonitrile [39], and p-xylene [40].
Molecules 28 04651 sch003 550
Scheme 3. DES–catalyzed arylation of benzoxazoles with aromatic aldehydes.
In a recent report, D’Amico et al. demonstrated the use of DES as a sustainable and benign solvent to directly arylate a series of 3,4-disubstituted thiophenes. These thiophenes are well-known for their wide range of applications in optoelectronics, from photovoltaics to semiconductors and electrochromes [41]. ChCl:glycerol (1:2) was chosen as the DES for its high biocompatibility and biodegradability [42] (Scheme 4). A catalytic system consisting of Pd(Cl)2 (x = 1–5 mol%), P(2-MeOPh)3 (2x mol%) as the ligand, PivOH (30 mol%) as additive, and K2CO3 (2.5 equiv.) as the base at 110 °C for 24 h could effectively diarylate 3,4-ethylenedioxythiophene 10 with aryl and heteroaryl bromides 11 in moderate-to-high yield of the target product 12. Air can promote the oxidation of Pd(0) to Pd(II) after the catalytic cycle of C–H activation reaction [43]. This allows palladium to be reused in subsequent cycles of the transformation. As a result of undertaking the reaction under air, there is no need to use inert gas atmospheres and the setup becomes much simpler. This can also reduce the environmental impact of the reaction by eliminating the need to purge the inert gas.
Molecules 28 04651 sch004 550
Scheme 4. Pd–catalyzed direct arylation of thienyl derivatives with (hetero)aromatic bromides in DESs.
In this strategy, electron poor bromides provided excellent yield even with low catalyst loading (1.0 mol%), while electron rich bromides needed more of the catalyst (5.0 mol%) for a good yield. Ortho-substituted bromides did not affect the reaction negatively, and heteroaromatic bromides, such as 2-bromopyridine, were moderately reactive. Note that simple recrystallization with EtOH or EtOAc is often sufficient for purification. Very recently, Vitale and colleagues reported a new strategy for synthesizing 1-arylpropan-2-ones in DESs under aerobic conditions (Scheme 5) [44]. These compounds are known for their pharmacological activity [45][46]. The group began their study by optimizing the conditions for preparing the enolate intermediate. They achieved this by subjecting 1-phenylpropan-2-one 13 to t-BuOK as the optimum base and ChCl:urea (1:2) as the eutectic mixture at room temperature for 1 h. Alkyls and alkenes 14 with different electronic natures were compatible and generated the desired α-substituted products 15 in high to excellent yields. A series of arylpropan-2-ones with fluorine or CF3 at ortho-, meta-, or para- position of aryl ring afforded moderate to high yields.
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Scheme 5. Synthesis of 1-arylpropan-2-ones in DES.
The authors arylated 1-phenylpropan-2-one 13 at room temperature for 1 h with t-BuOK (3 equiv.) as the base, and ChCl:urea (1:2) as the solvent. Then, they added iodoaryls or bromoaryls 14 (1.1 equiv.) and Pd[P(t-Bu)3]2 (5–10 mol%) to the mixtures and heated it at 45–70 °C for 2–12 h. The yield of the products ranged from moderate to excellent, with iodoaryls more reactive than aryl bromides. DESs have shown great potential in activating carbonyl-containing substrates for alpha-arylation. The activation process involves the formation of a hydrogen bond between the carbonyl group of the substrate and the HBD moiety of the DES. This interaction enhances the electrophilicity of the carbonyl group, facilitating the formation of the desired α-substituted product [47][48]. Nawaz Khan et al. developed a novel approach for sp3-CH functionalization of acetophenones 16 with benzyl alcohols 17 using DES [49]. The optimized conditions include Pd(PPh3)4/xantphos as the catalyst/ligand combination and KOtBu (1.5 equiv.) as the base. Among the DESs used, ChCl:malonic acid (1:1) was found to be the most effective solvent, producing high yields of the α,β-saturated ketones 18 (Scheme 6). The use of ChCl−oxalic acid (1:1) as the DES mixture also led to the desired product in good yields. A variety of electron donating and electron withdrawing groups were tolerated on acetophenone and benzyl alcohol to isolate the desired α,β-saturated ketones in good to high yields. By using the ChCl-based DESs as alternatives to toluene, the acidic pH of the DESs neutralized the reaction medium from strongly basic to slightly basic. This adjustment reduced the likelihood of ketone reduction into alcohols and the formation of side products. The mechanism of DES involves hydrogen bonding, activating benzyl alcohol before dehydrogenation catalyzed by the palladium complex. The DES medium enhances electrophilicity by interacting with the oxygen atom of the ketone group, promoting the nucleophilic attack to form an α-alkylated saturated ketone 18.
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Scheme 6. Palladium-catalyzed sp3 C–H functionalization of methyl ketones.
The Friedländer reaction between ketone 19 and acetylacetone 20 suggests that DES acted as both the solvent and catalyst. The DES formed hydrogen bonds with the reagents, facilitating the reaction, and the formation of a chalcone intermediate was observed [50]. The reaction involved an N-heterocyclic ketone that was 4-α-alkylated with benzyl alcohols 21, resulting in a good yield of the desired product 22. Various substituents on benzyl alcohol were compatible and steric hindrance had no effect on the reaction yield (Scheme 7). DES was reused for five consecutive cycles, with no observable detrimental effects on yields.
Molecules 28 04651 sch007 550
Scheme 7. Friedländer reaction and palladium-catalyzed, sp3 C–H functionalization of methyl ketones.
Marset recently described a strategy for the free-silver-mediated Csp3–H functionalization of unactivated 8-aminoquinoline amides using palladium catalysts in a DES [51]. He established the conditions for functionalizing the amide derived from 8-aminoquinoline 23 with aryl iodides 24. The conditions involved Pd(OAc)2 (10 mol%) as the catalyst, NaHCO3 (1.5 equiv.) as the base, and 2-pyridone (40 mol%) as the ligand. The reaction was carried out in betaine (choline derivative):hexafluoroisopropanol (HFIP) (1:2) as the solvent at 110 °C for 2.5 h, resulting in a good to high yields of the desired products 25. Additionally, ChCl:acetamide (1:2) also proved effective among the various DESs evaluated, providing the desired products in good yields (Scheme 8).
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Scheme 8. Arylation of amide derived from 8-aminoquinoline.
The protocol was efficient with aryl iodides that had both electron withdrawing and electron donating groups in betaine:HFIP (1:2) and ChCl:acetamide (1:2) DESs, resulting in good to excellent yields. Betaine:HFIP provided higher yields. However, ortho-substituted aryl iodides had drastic results due to steric hindrance. In ChCl:acetamide (1:2), shorter alkyl-chain lengths resulted in marginal yields, while full conversions were obtained in betaine:HFIP (1:2). Furthermore, a one-pot directing group removal was presented by quenching the reaction with 40% aqueous sulfuric acid [52] and heating the mixture at 110 °C for 24 h, affording 28 in a good yield (Scheme 9). Although the reusability of DESs with the catalyst may be limited to no more than two cycles, DESs can facilitate the recycling of transition-metal catalysts in multiple reaction processes. This can result in a substantial enhancement of the overall turnover number of reactions [53][54].
Molecules 28 04651 sch009 550
Scheme 9. One-pot directing group removal.
Recently, in 2022, a research team led by González–Gallardo published a study on a highly effective method for C–H activation using a ruthenium catalyst in DESs [55]. The optimized conditions for the reaction involved 3 mol% [RuCl2(p-cymene)]2 as the catalyst, and 20 mol% NaOAc as an additive, at 70 °C for 16 h. After examining various DESs, ChCl:ethylene glycol (1:2) was the most effective solvent. Choline chloride-based DESs are highly polar solvents that can increase reaction rates and stabilize reactive intermediates, making them effective for polar reactions [56]. Electron withdrawing substituents on the para position of N-methoxybenzamide 29 reacted with internal alkynes with aromatic substituents 30 and favored the desired isoquinolones with high yields 31 (Scheme 10). The DES can be reused for up to three times without any significant loss in yield. Isoquinolone derivatives have displayed various pharmacological and biological effects, including antitumor [57], anti-inflammatory [58], and antihypertensive activities [59].
Molecules 28 04651 sch010 550
Scheme 10. C–H activation reaction using disubstituted alkynes and electron poor olefins.
The C–H activation reaction with N-methoxybenzamide 29 proved effective for electron poor olefins 32 under identical conditions. High yields were achieved when utilizing olefins containing electron withdrawing groups. Interestingly, exceptional Michael acceptor reagents, such as vinyl ketone and phenyl–vinyl, sulfone-generated cyclic products 33, or a mixture of acyclic and cyclic products 33 and 34, had excellent yields (Scheme 10). To assess the flexibility of this approach, Cu(OAc)2 (10 mol%) was used instead of NaOAC, and betaine:HFIP (1:2) was chosen as the solvent among various DESs tested. A variety of olefins 36, containing electron withdrawing groups, reacted with benzoic acid 35, leading to high yields of the products 37 and 38. Electron withdrawing substituents at the para position in the carboxylic acid 35 favored the reaction, while electron donating groups showed lower reactivity. Experiments were conducted using various disubstituted alkynes 39 to create isocoumarin derivatives 40. Isocoumarin scaffolds are a group of natural products that are biologically, structurally, pharmacologically fascinating, and commonly used in drug discovery, pharmaceutical and medical chemistry [60][61]. Good yields were obtained when carboxylic acids were subjected to internal alkynes with aromatic, aryl–alkyl, and alkyl–alkyl substituents 39 (Scheme 11).
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Scheme 11. C–H activation reaction using electron poor olefins and disubstituted alkynes with benzoic acid derivatives.
Successful synthesis of heterocycles commonly found in drug candidates [62] was achieved by reacting 2-thiophenecarboxylic acid 41 with various olefins 42 containing electron withdrawing groups. Every reaction produced moderate to good yields of exclusively acyclic derivatives 43. To demonstrate the method’s applicability, the reaction was scaled up to the gram level, resulting in excellent yield of the desired product through precipitation with a small amount of water (Scheme 12). The reaction was conducted under air conditions, air can act as an oxidant to make the reaction more cost-effective and safer than other commonly used oxidants, such as peroxides or molecular oxygen.
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Scheme 12. C–H activation reaction using electron poor olefins with 2-thiophenecarboxylic acid.
Under the previously mentioned conditions, and to broaden the range of substrates for this transformation, several aryl pyrazole derivatives 44 and electron poor olefins 45 were tested, resulting in moderate to good yields. Interestingly, the use of methyl–vinyl ketone as a substrate, led to the production of both saturated 46 and unsaturated compounds 47 in similar proportions. Additionally, in some instances, a double addition product to 1-phenylpyrazole 48 was observed (Scheme 13). Certain arylpyrazoles have exhibited noteworthy pharmacological activities [63].
Molecules 28 04651 sch013 550
Scheme 13. C–H activation reaction using electron poor olefins with 1-arylpyrazole derivatives.

References

  1. Laird, T. Green Chemistry Is Good Process Chemistry. Org. Process Res. Dev. 2012, 16, 1–2.
  2. Kemeling, G.M. Editorial: Solvent Choices and Sustainable Chemistry. ChemSusChem 2012, 5, 2291–2292.
  3. Burrow, C.J.; Harper, J.B.; Sander, W.; Tantillo, D.J. Solvation E Ff Ects in Organic Chemistry. J. Org. Chem. 2022, 87, 1599–1601.
  4. Ahmad, N.; Ahmad, F. Green Chemistry: Principle and Its Application. In Proceedings of the 2nd International Conference on Advancement in Engineering, Applied Science and Management (ICAEASM-2017), New Delhi, India, 2 July 2017.
  5. Anastas, P.T.; Warner, J.C. Memorandum of Understanding of the 12 Principles of Green Chemistry; American Chemical Society Green Chemistry Institute: Washington, DC, USA, 2010; pp. 29–30.
  6. Seltzer, K.M.; Pennington, E.; Rao, V.; Murphy, B.N.; Strum, M.; Isaacs, K.K.; Pye, H.O.T. Reactive Organic Carbon Emissions from Volatile Chemical Products. Atmos. Chem. Phys. 2021, 21, 5079–5100.
  7. Amelio, A.; Genduso, G.; Vreysen, S.; Luis, P.; Van Der Bruggen, B. Guidelines Based on Life Cycle Assessment for Solvent Selection during the Process Design and Evaluation of Treatment Alternatives. Green Chem. 2014, 16, 3045–3063.
  8. Jing, A.; Kumar, V.; Kannan, K. Environmental Chemistry and Ecotoxicology A Review of Environmental Occurrence, Toxicity, Biotransformation and Biomonitoring of Volatile Organic Compounds. Environ. Chem. Ecotoxicol. 2021, 3, 91–116.
  9. Roy, W.R. Environmental Impact of Solvents. Handb. Solvents 2014, 2, 361–385.
  10. Lee, H.; Kim, K.; Choi, Y.; Kim, D. Emissions of Volatile Organic Compounds (VOCs) from an Open-Circuit Dry Cleaning Machine Using a Petroleum-Based Organic Solvent: Implications for Impacts on Air Quality. Atmosphere 2021, 12, 637.
  11. Anastas, P.T.; Kirchhoff, M.M. Origins, Current Status, and Future Challenges of Green Chemistry. Acc. Chem. Res. 2002, 35, 686–694.
  12. Constable, D.J.C.; Jimenez-Gonzalez, C.; Henderson, R.K. Perspective on Solvent Use in the Pharmaceutical Industry. Org. Process Res. Dev. 2007, 11, 133–137.
  13. Abranches, D.O.; Coutinho, J.A.P. Type V Deep Eutectic Solvents: Design and Applications. Curr. Opin. Green Sustain. Chem. 2022, 35, 100612.
  14. Smith, E.L.; Abbott, A.P.; Ryder, K.S. Deep Eutectic Solvents (DESs) and Their Applications. Chem. Rev. 2014, 114, 11060–11082.
  15. Farooq, M.Q.; Abbasi, N.M.; Anderson, J.L. Deep Eutectic Solvents in Separations: Methods of Preparation, Polarity, and Applications in Extractions and Capillary Electrochromatography. J. Chromatogr. A 2020, 1633, 461613.
  16. Tang, B.; Row, K.H. Recent Developments in Deep Eutectic Solvents in Chemical Sciences. Mon. Fur Chem. 2013, 144, 1427–1454.
  17. El Abbouchi, A.; Koubachi, J.; Brahmi, N. El Direct Arylation and Suzuki-Miyaura Coupling of Imidazo Pyridines Catalyzed by (SIPr) Pd (Allyl) Cl Complex Under. Mediterr. J. Chem. 2019, 9, 347–354.
  18. Gambouz, K.; El Abbouchi, A.; Nassiri, S.; Suzenet, F.; Bousmina, M.; Akssira, M.; Guillaumet, G.; El Kazzouli, S. “On Water” Palladium Catalyzed Direct Arylation of 1H-Indazole and 1H-7-Azaindazole. Molecules 2020, 25, 2820.
  19. Koubachi, J.; El Kazzouli, S.; Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G. New and Efficient Palladium(0)-Mediated Microwave-Assisted Direct C3 Alkenylation of ImidazoPyridines. Synthesis 2008, 16, 2537–2542.
  20. El Kazzouli, S.; Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G. Synthesis and Functionalization of ImidazoPyridines and ImidazoPyrimidines on Solid Phase Using Suzuki-Miyaura Cross-Coupling Reactions. Lett. Org. Chem. 2012, 9, 118–127.
  21. Berteina-raboin, S.; Mouaddib, A. Regioselective Palladium-Catalyzed Arylation and Heteroarylation of Imidazo Pyridines. Synlett 2006, 19, 3237–3242.
  22. Lavrard, H.; Popowycz, F. Regioselective Late-Stage C-3 Functionalization of Pyrazolo- Pyridines. Synthesis 2018, 50, 998–1006.
  23. Faarasse, S.; El Kazzouli, S.; Naas, M.; Jouha, J.; Suzenet, F.; Guillaumet, G. “On Water” Direct C-3 Arylation of 2H-PyrazoloPyridines. J. Org. Chem. 2017, 82, 12300–12306.
  24. Faarasse, S.; El Kazzouli, S.; Suzenet, F.; Guillaumet, G. Palladium-Catalyzed C3-Arylations of 1H- and 2H-PyrazoloPyridines on Water. J. Org. Chem. 2018, 83, 12847–12854.
  25. Boujdi, K.; El Brahmi, N.; Graton, J.; Dubreuil, D.; Collet, S.; Mathé-Allainmat, M.; Akssira, M.; Lebreton, J.; El Kazzouli, S. A Regioselective C7 Bromination and C7 Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling Arylation of 4-Substituted NH-Free Indazoles. RSC Adv. 2021, 11, 7107–7114.
  26. Paquin, F.; Rivnay, J.; Salleo, A.; Stingelin, N.; Silva, C. Multi-Phase Semicrystalline Microstructures Drive Exciton Dissociation in Neat Plastic Semiconductors. J. Mater. Chem. C 2015, 3, 10715–10722.
  27. Ben-Yahia, A.; Naas, M.; El Kazzouli, S.; Essassi, E.M.; Guillaumet, G. Direct C-3-Arylations of 1H-Indazoles. Eur. J. Org. Chem. 2012, 36, 7075–7081.
  28. Faarasse, S.; El Brahmi, N.; Guillaumet, G.; El Kazzouli, S. Ring of the 6, 5-Fused Heterocyclic Systems: An Overview. Molecules 2021, 26, 5763.
  29. Koubachi, J.; El Brahmi, N.; Guillaumet, G.; El Kazzouli, S. Oxidative Alkenylation of Fused Bicyclic Heterocycles. Eur. J. Org. Chem. 2019, 2019, 2568–2586.
  30. Naas, M.; El Kazzouli, S.; Essassi, E.M.; Bousmina, M.; Guillaumet, G. Palladium-Catalyzed Oxidative Direct C3- and C7-Alkenylations of Indazoles: Application to the Synthesis of Gamendazole. Org. Lett. 2015, 17, 4320–4323.
  31. Liu, P.; Hao, J.W.; Mo, L.P.; Zhang, Z.H. Recent Advances in the Application of Deep Eutectic Solvents as Sustainable Media as Well as Catalysts in Organic Reactions. RSC Adv. 2015, 5, 48675–48704.
  32. Punzi, A.; Coppi, D.I.; Matera, S.; Capozzi, M.A.M.; Operamolla, A.; Ragni, R.; Babudri, F.; Farinola, G.M. Pd-Catalyzed Thiophene-Aryl Coupling Reaction via C-H Bond Activation in Deep Eutectic Solvents. Org. Lett. 2017, 19, 4754–4757.
  33. Shariatipour, M.; Salamatmanesh, A.; Jadidi Nejad, M.; Heydari, A. Imidazole-Aryl Coupling Reaction via CH Bond Activation Catalyzed by Palladium Supported on Modified Magnetic Reduced Graphene Oxide in Alkaline Deep Eutectic Solvent. Catal. Commun. 2020, 135, 105890.
  34. Naser, J.; Mjalli, F.; Jibril, B.; Al-Hatmi, S.; Gano, Z. Potassium Carbonate as a Salt for Deep Eutectic Solvents. Int. J. Chem. Eng. Appl. 2013, 4, 114–118.
  35. Tran, P.H.; Thi Hang, A.H. Deep Eutectic Solvent-Catalyzed Arylation of Benzoxazoles with Aromatic Aldehydes. RSC Adv. 2018, 8, 11127–11133.
  36. Links, D.A.; Liu, S.; Chen, R.; Guo, X.; Yang, H.; Deng, G.; Li, C. Iron-Catalyzed Arylation of Benzoazoles with Aromatic Aldehydes Using Oxygen. Green Chem. 2012, 14, 1577–1580.
  37. Teo, Y.C.; Riduan, S.N.; Zhang, Y. Iodine-Mediated Arylation of Benzoxazoles with Aldehydes. Green Chem. 2013, 15, 2365–2368.
  38. Zhu, F.; Tao, J.; Wang, Z. Palladium-Catalyzed C−H Arylation of (Benzo)Oxazoles or (Benzo)Thiazoles with Aryltrimethylammonium Tri Fl Ates. Org. Lett. 2015, 17, 4926–4929.
  39. Kim, D.; Yoo, K.; Kim, S.E.; Cho, H.J.; Lee, J.; Kim, Y.; Kim, M. Copper-Catalyzed Selective Arylations of Benzoxazoles with Aryl Iodides. J. Org. Chem. 2015, 80, 3670–3676.
  40. Steinberg, D.F.; Turk, M.C.; Kalyani, D. Nickel-Catalyzed C−H Arylation of Benzoxazoles and Oxazoles: Benchmarking the Influence of Electronic, Steric and Leaving Group Variations in Phenolic Electrophiles. Tetrahedron 2017, 73, 2196–2209.
  41. D’Amico, F.; Papucci, C.; Franchi, D.; Reginato, G.; Calamante, M.; Zani, L.; Dessì, A.; Mordini, A. Sustainable Pd-Catalyzed Direct Arylation of Thienyl Derivatives with (Hetero)Aromatic Bromides under Air in Deep Eutectic Solvents. ACS Sustain. Chem. Eng. 2022, 10, 3037–3047.
  42. Zhao, B.Y.; Xu, P.; Yang, F.X.; Wu, H.; Zong, M.H.; Lou, W.Y. Biocompatible Deep Eutectic Solvents Based on Choline Chloride: Characterization and Application to the Extraction of Rutin from Sophora Japonica. ACS Sustain. Chem. Eng. 2015, 3, 2746–2755.
  43. Chen, X.; Engle, K.M.; Wang, D.H.; Jin-Quan, Y. Palladium(II)-CataIyzed C-H Aetivation/C-C Cross-Coupling Reactions: Versatility and Practicality. Angew. Chem. Int. Ed. 2009, 48, 5094–5115.
  44. Vitale, P.; Cicco, L.; Perna, F.M.; Capriati, V. Introducing Deep Eutectic Solvents in Enolate Chemistry: Synthesis of 1-Arylpropan-2-Ones under Aerobic Conditions. React. Chem. Eng. 2021, 6, 1796–1800.
  45. Vitale, P.; Tacconelli, S.; Perrone, M.G.; Malerba, P.; Simone, L.; Scilimati, A.; Lavecchia, A.; Dovizio, M.; Marcantoni, E.; Bruno, A.; et al. Synthesis, Pharmacological Characterization, and Docking Analysis of a Novel Family of Diarylisoxazoles as Highly Selective Cyclooxygenase-1 (COX-1) Inhibitors. J. Med. Chem. 2013, 56, 4277–4299.
  46. Perrone, M.G.; Vitale, P.; Panella, A.; Fortuna, C.G.; Scilimati, A. General Role of the Amino and Methylsulfamoyl Groups in Selective Cyclooxygenase(COX)-1 Inhibition by 1,4-Diaryl-1,2,3-Triazoles and Validation of a Predictive Pharmacometric PLS Model. Eur. J. Med. Chem. 2015, 94, 252–264.
  47. Saavedra, B.; Ramón, D.J. Deep Eutectic Solvent as a Sustainable Medium for C-C Bond Formation Via Multicomponent Radical Conjugate Additions. ACS Sustain. Chem. Eng. 2021, 9, 7941–7947.
  48. Nomura, K.; Terwilliger, P. Self-Dual Leonard Pairs Use of Deep Eutectic Solvents as Catalyst: A mini-review. Green Process. Synth. 2019, 8, 355–372.
  49. Teja, C.; Nawaz Khan, F.R. Choline Chloride-Based Deep Eutectic Systems in Sequential Friedländer Reaction and Palladium-Catalyzed Sp3 CH Functionalization of Methyl Ketones. ACS Omega 2019, 4, 8046–8055.
  50. Schlepphorst, C.; Maji, B.; Glorius, F. Ruthenium-NHC Catalyzed α-Alkylation of Methylene Ketones Provides Branched Products through Borrowing Hydrogen Strategy. ACS Catal. 2016, 6, 4184–4188.
  51. Marset, X. Palladium-Catalysed Csp3-H Functionalisation of Unactivated 8-Aminoquinoline Amides in Deep Eutectic Solvents. Org. Biomol. Chem. 2022, 20, 7071–7075.
  52. Larrosa, M.; Heiles, S.; Becker, J.; Spengler, B.; Hrdina, R. C-H Bond Arylation of Diamondoids Catalyzed by Palladium(II) Acetate. Adv. Synth. Catal. 2016, 358, 2163–2171.
  53. Marset, X.; Khoshnood, A.; Sotorríos, L.; Gómez-Bengoa, E.; Alonso, D.A.; Ramón, D.J. Deep Eutectic Solvent Compatible Metallic Catalysts: Cationic Pyridiniophosphine Ligands in Palladium Catalyzed Cross-Coupling Reactions. ChemCatChem 2017, 9, 1269–1275.
  54. Marset, X.; Guillena, G.; Ramón, D.J. Deep Eutectic Solvents as Reaction Media for the Palladium-Catalysed C−S Bond Formation: Scope and Mechanistic Studies. Chem. Eur. J. 2017, 23, 10522–10526.
  55. González-Gallardo, N.; Saavedra, B.; Guillena, G.; Ramón, D.J. A Jackpot C-H Activation Protocol Using Simple Ruthenium Catalyst in Deep Eutectic Solvents. Green Chem. 2022, 24, 4941–4951.
  56. Pandey, A.; Rai, R.; Pal, M.; Pandey, S. How Polar Are Choline Chloride-Based Deep Eutectic Solvents? Phys. Chem. Chem. Phys. 2014, 16, 1559–1568.
  57. Berger, M.; Rehwinkel, H.; Schmees, N.; Schäcke, H.; Edman, K.; Wissler, L.; Reichel, A.; Jaroch, S. Discovery of New Selective Glucocorticoid Receptor Agonist Leads. Bioorg. Med. Chem. Lett. 2017, 27, 437–442.
  58. Bosanac, T.; Hickey, E.R.; Ginn, J.; Kashem, M.; Kerr, S.; Kugler, S.; Li, X.; Olague, A.; Schlyer, S.; Young, E.R.R. Substituted 2H-Isoquinolin-1-Ones as Potent Rho-Kinase Inhibitors: Part 3, Aryl Substituted Pyrrolidines. Bioorg. Med. Chem. Lett. 2010, 20, 3746–3749.
  59. Lee, H.; Ahn, S.; Ann, J.; Ha, H.; Yoo, Y.D.; Kim, Y.H.; Hwang, J.Y.; Hur, K.H.; Jang, C.G.; Pearce, L.V.; et al. Discovery of Dual-Acting Opioid Ligand and TRPV1 Antagonists as Novel Therapeutic Agents for Pain. Eur. J. Med. Chem. 2019, 182, 111634.
  60. Shabir, G.; Saeed, A.; El-Seedi, H.R. Phytochemistry Natural Isocoumarins: Structural Styles and Biological Activities, the Revelations Carry on …. Phytochemistry 2021, 181, 112568.
  61. Saeed, A. Isocoumarins, Miraculous Natural Products Blessed with Diverse Pharmacological Activities. Eur. J. Med. Chem. 2016, 116, 290–317.
  62. Meanwell, N.A. Improving Drug Candidates by Design: A Focus on Physicochemical Properties as a Means of Improving Compound Disposition and Safety. Chem. Res. Toxicol. 2011, 24, 1420–1456.
  63. Brown, A.W.; Fisher, M.; Tozer, G.M.; Kanthou, C.; Harrity, J.P.A. Sydnone Cycloaddition Route to Pyrazole-Based Analogs of Combretastatin A4. J. Med. Chem. 2016, 59, 9473–9488.
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