Ligand‐Free Copper‐Catalyzed Ullmann‐Type C−O Bond Formation in Non‐Innocent Deep Eutectic Solvents under Aerobic Conditions

Quivelli, Andrea Francesca; Marinò, Manuela; Vitale, Paola; García‐Álvarez, Joaquín; Perna, Filippo Maria; Capriati, Vito

doi:10.1002/cssc.202102211

Cited by 15 publications

(8 citation statements)

References 76 publications

(27 reference statements)

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“…Furthermore, taking advantage of some peculiar properties like high viscosity, conductivity, and polarity, as well as high solubility in water, which usually simplify the isolation of the final products, DESs have been successfully employed as alternatives to VOCs in many organic and organometallic transformations. − For example, the employment of polar organometallic reagents like alkyl- and aryllithium species , in DESs has been successfully proven under mild conditions and very short reaction times. A very important class of transformations that were positively affected by the use of DESs consist of cross-coupling reactions, as reported for Suzuki–Miyaura, − Sonogashira, ,, Hiyama, , Negishi, Stille–Migita, and Ullmann-type − reactions, which have been extensively investigated in recent years.…”

Section: Introductionmentioning

confidence: 99%

Sustainable Pd-Catalyzed Direct Arylation of Thienyl Derivatives with (Hetero)aromatic Bromides under Air in Deep Eutectic Solvents

D’Amico

Papucci

Franchi

et al. 2022

ACS Sustainable Chem. Eng.

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An optimized protocol for the Pd-catalyzed direct arylation of 3,4-ethylenedioxythiophene (EDOT) and other substituted thiophenes with (hetero)aromatic bromides in a deep eutectic solvent made of a mixture of choline chloride/glycerol (1:2) is presented. The coupling reactions have been successfully run under air, in nonanhydrous conditions, using PdCl 2 as a palladium source, with a catalyst loading as low as 1 mol %. The adjustment of each reaction component allowed finding robust conditions for the introduction of both electron-poor and electronrich (hetero)aryl bromides with moderate-to-high yields. The sustainability of the protocol was established through calculations of green metrics, such as Eco-scale and E-factor, and compared with the literature, when possible. Remarkably, such procedure can be successfully applied for the simple preparation of conjugated organic compounds with potential applications in optoelectronics, as we have shown, by obtaining two molecules previously reported as a hole transport material for perovskite solar cells and the final intermediate of a photosensitizer for dye-sensitized solar cells.

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Section: Introductionmentioning

confidence: 99%

Sustainable Pd-Catalyzed Direct Arylation of Thienyl Derivatives with (Hetero)aromatic Bromides under Air in Deep Eutectic Solvents

D’Amico

Papucci

Franchi

et al. 2022

ACS Sustainable Chem. Eng.

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“…This is why identification and characterization of impurities are of pivotal importance for the development of a good manufacturing procedure, even if this is often challenging . Under the best conditions previously found for the synthesis of aromatic amines in DESs (CuI 10 mol %, t -BuOK 3 equiv, 100 °C, 12 h in ChCl/Gly), the reaction between 2-bromopyridine ( 9a ) (0.5 mmol) and diamine 8a (1 equiv) provided Thenfadil 3a in 10% yield only, along with two main side products, 2,2′-oxydipyridine ( 11 ) (46% yield) and 3-(pyridin-2-yloxy)propane-1,2-diol ( 12 ) (32% yield) ( 1 H NMR analysis), the latter being most probably the result of a competitive Ullmann-type C–O coupling reaction (Table , entry 1) . It was also found that the yield of 3a could be increased up to 30% by decreasing the temperature to 60 °C, but the formation of 11 still competed strongly (40% yield) (Table , entry 2).…”

Section: Resultsmentioning

confidence: 99%

Sustainable and Scalable Two-Step Synthesis of Thenfadil and Some Analogs in Deep Eutectic Solvents: From Laboratory to Industry

Quivelli

Rossi²,

Vitale

et al. 2022

ACS Sustainable Chem. Eng.

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A sustainable two-step protocol was developed for the synthesis of the antihistamine drug Thenfadil by combining a reductive amination process with a Cu-catalyzed Ullmann-type C− N coupling reaction run in environmentally responsible deep eutectic solvents (DESs), constructed from biobased compounds. Under optimized conditions, both reactions proceed smoothly under aerobic conditions and in the absence of any additional ligand, with the desired active pharmaceutical ingredient isolated in an overall reaction yield of 39% with an effective suppression of the side products arising from competitive Cu-catalyzed C−O coupling reactions. A novel and simplified workup procedure has also been set up, which avoids the need for chromatographic purification, while allowing the recovery and the recycling of the unreacted intermediate secondary amine. The potential application and the robustness of the proposed methodology has been demonstrated (a) in scale-up studies up to 50 g of substrate in 0.5 kg of DES, taking place with no decrease in the reaction yield, and (b) in the synthesis of three other ethylenediamine derivatives (Thenfadil's analogs) like tripelennamine, methaphenilene, and thonzylamine in 39%−44% overall yield. Typical metrics applied at First and Second Pass, according to the CHEM21 Metrics Toolkit, have been calculated as well for the whole synthetic procedure of Thenfadil and results compared with those of the classical procedure.

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“…Specifically, mixtures of ChCl with HBD, such as ethylene glycol, glycerol, 1,3-propanediol or lactic acid, were employed as solvents and reagents to be coupled with aryl bromides or iodides, using CuI as a catalyst and K 2 CO 3 as a base at 80 °C for 6 h. Three pharmacologically active compounds were obtained, with gram-scale synthesis being feasible. In addition, the catalyst, DES and base system could be reused for up to seven cycles without an important catalytic decrease ( Figure 28 ) [ 83 ]. Heterogeneous C-O coupling has also been reported with Cu(I)-Benzoylthiophene-SiO 2 @Fe 3 O 4 [ 84 ].…”

Section: Cross-coupling Reactionsmentioning

confidence: 99%

Deep Eutectic Solvents as à-la-Carte Medium for Transition-Metal-Catalyzed Organic Processes

Marset

Guillena

2022

Molecules

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Our society is facing a tremendous challenge to become more sustainable in every sphere of life. Regarding the chemical industry, one of the most significant issues to be addressed is the use of volatile organic compounds (VOCs) as solvents because they are petrol-derived and most of them are toxic and flammable. Among the possible solutions, deep eutectic solvents (DESs) have emerged as sustainable alternatives to VOCs in organic catalyzed transformations and other fields. The advantages of these new reaction media are not only related to their more benign physical and chemical properties and, for most of them, their renewable sources but also due to the possibility of being recycled after their use, increasing the sustainability of the catalyzed process in which they are involved. However, their use as media in catalytic transformations introduces new challenges regarding the compatibility and activity of known catalysts. Therefore, designed catalysts and “à-la-carte” DESs systems have been developed to overcome this problem, to maximize the reaction outcomes and to allow the recyclability of the catalyst/media system. Over the last decade, the popularity of these solvents has steadily increased, with several examples of efficient metal-catalyzed organic transformations, showing the efficiency of the catalysts/DES system, compared to the related transformations carried out in VOCs. Additionally, due to the inherent properties of the DES, unknown transformations can be carried out using the appropriated catalyst/DES system. All these examples of sustainable catalytic processes are compiled in this review.

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Ligand‐Free Copper‐Catalyzed Ullmann‐Type C−O Bond Formation in Non‐Innocent Deep Eutectic Solvents under Aerobic Conditions

Cited by 15 publications

References 76 publications

Sustainable Pd-Catalyzed Direct Arylation of Thienyl Derivatives with (Hetero)aromatic Bromides under Air in Deep Eutectic Solvents

Sustainable Pd-Catalyzed Direct Arylation of Thienyl Derivatives with (Hetero)aromatic Bromides under Air in Deep Eutectic Solvents

Sustainable and Scalable Two-Step Synthesis of Thenfadil and Some Analogs in Deep Eutectic Solvents: From Laboratory to Industry

Deep Eutectic Solvents as à-la-Carte Medium for Transition-Metal-Catalyzed Organic Processes

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