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The design of a hybrid one-pot tandem protocol through the combination of biodeoximations (promoted by laccase from Trametes versicolor) and s-block polar organometallics (RLi/RMgX) in aqueous media, at room temperature and under air is reported.

University of Bari "Aldo Moro" [2017A5HXFC 002, 2020SBNHLH]; Interuniversity Consortium C.I.N.M.P.I.S. [2017A5HXFC 002, 2020SBNHLH]; Ministero dell'Universita e della Ricerca (MUR-PRIN) [2017A5HXFC 002, 2020SBNHLH]; MCIN/AEI [PID2020-113473GB I00]; Programa Severo Ochoa para la formación en investigación y docencia del Principado de Asturias [PA-21-PF-BP20-093, PA-22-PF-BP21-088]

Pd-catalyzed Negishi cross-coupling reactions between organozinc compounds and (hetero)aryl bromides have been reported when using bulk water as the reaction medium in the presence of NaCl or the biodegradable choline chloride/urea eutectic mixture. Both C(sp3 )-C(sp2 ) and C(sp2 )-C(sp2 ) couplings have been found to proceed smoothly, with high chemoselectivity, under mild conditions (room temperature or 60 °C) in air, and in competition with protonolysis. Additional benefits include very short reaction times (20 s), good to excellent yields (up to 98 %), wide substrate scope, and the tolerance of a variety of functional groups. The proposed novel protocol is scalable, and the practicability of the method is further highlighted by an easy recycling of both the catalyst and the eutectic mixture or water.

Owing to a growing awareness towards environmental impact, the search for "greener", safer, and cost-effective solvents able to replace petroleum-derived solvents has never been greater today. In this context, the use of environmentally responsible solvents like water and the so-called deep eutectic solvents (DESs), constructed from bio-based compounds, has recently experienced important growth in several fields of sciences. This short review highlights the key features of the chemistry of water and (hydrated) DESs when applied to metal- and biocatalyzed transformations as well as to the synthesis of active pharmaceutical ingredients (APIs) and other biologically relevant compounds by providing, through discussion of all relevant literature over the past five years, a comparison of the outcomes of the reactions when carried out in one or the other solvent.

Alkoxide-mediated enolization of 1-arylpropan-2-ones and their fluorinated derivatives, followed by α-functionalization with nucleophilic addition and substitution reactions, has been accomplished in the environmentally friendly eutectic mixture choline chloride/urea, under aerobic conditions. The usefulness of this new protocol has also been exemplified through the synthesis of a small selection of building-block like molecules through Pd-catalyzed α-arylation reactions.

The one-pot/two-step combination of enzymes and polar organometallic chemistry in aqueous media is for the first time presented as a proof-of-concept study. The unprecedented combination of the catalytic oxidation of secondary alcohols by the system laccase/TEMPO with the ultrafast addition (3 s reaction time) of polar organometallic reagents (RLi/RMgX) to the in situ formed ketones, run under air at room temperature, allows the straightforward and chemoselective synthesis of tertiary alcohols with broad substrate scope and excellent conversions (up to 96%).

We report that phenacyl azides are key compounds for a regiodivergent synthesis of valuable, functionalized imidazole (32–98% yield) and pyrimidine derivatives (45–88% yield), with a broad substrate scope, when using deep eutectic solvents [choline chloride (ChCl)/glycerol (1:2 mol/mol) and ChCl/urea (1:2 mol/mol)] as environmentally benign and non-innocent reaction media, by modulating the temperature (25 or 80 °C) in the presence or absence of bases (Et3N).

Highly polarized organometallic compounds of s-block elements are added smoothly to chiral N-tert-butanesulfinyl imines in the biodegradable d-sorbitol/choline chloride eutectic mixture, thereby granting access to enantioenriched primary amines after quantitatively removing the sulfinyl group. The practicality of the method is further highlighted by proceeding at ambient temperature and under air, with very short reaction times (2 min), enabling the preparation of diastereoisomeric sulfinamides in very good yields (74-98 %) and with a broad substrate scope, and the possibility of scaling up the process. The method is demonstrated in the asymmetric syntheses of both the chiral amine side-chain of (R,R)-Formoterol (96 % ee) and the pharmaceutically relevant (R)-Cinacalcet (98 % ee).

Deep Eutectic Solvents (DESs) have been widely used in many fields to exploit their ecofriendly characteristics, from green synthetic procedures to environmentally benign industrial methods. In contrast, their application in emerging solar technologies, where the abundant and clean solar energy is used to properly respond to most important societal needs, is still relatively scarce. This represents a strong limitation since many solar devices make use of polluting or toxic components, thus seriously hampering their eco-friendly nature. Herein, we review the literature, mainly published in the last few years, on the use of DESs in representative solar technologies, from solar plants to last generation photovoltaics, featuring not only their passive role as green solvents, but also their active behavior arising from their peculiar chemical nature. This collection highlights the increasing and valuable role played by DESs in solar technologies, in the fulfillment of green chemistry requirements and for performance enhancement, in particular in terms of long-term temporal stability.

The development of biorefinery approaches is of great relevance for the sustainable production of valuable compounds. In accordance with circular economy principles, waste cooking oils (WCOs) are renewable resources and biorefinery feedstocks, which contribute to a reduced impact on the environment. Frequently, this waste is wrongly disposed of into municipal sewage systems, thereby creating problems for the environment and increasing treatment costs in wastewater treatment plants. In this study, regenerated WCOs, which were intended for the production of biofuels, were transformed through a chemo-enzymatic approach to produce hydroxy fatty acids, which were further used in polycondensation reaction for polyester production. Escherichia coli whole cell biocatalyst containing the recombinantly produced Elizabethkingia meningoseptica Oleate hydratase (Em_OhyA) was used for the biocatalytic hydration of crude WCOs-derived unsaturated free fatty acids for the production of hydroxy fatty acids. Further hydrogenation reaction and methylation of the crude mixture allowed the production of (R)- 10-hydroxystearic acid methyl ester that was further purified with a high purity (90%), at gram scale. The purified (R)- 10-hydroxystearic acid methyl ester was polymerized through a polycondensation reaction to produce the corresponding polyester. This work highlights the potential of waste products to obtain bio-based hydroxy fatty acids and polyesters through a biorefinery approach.

An efficient and novel protocol was developed for a Cu-catalyzed Ullmann-type aryl alkyl ether synthesis by reacting various (hetero)aryl halides (Cl, Br, I) with alcohols as active components of environmentally benign choline chloride-based eutectic mixtures. Under optimized conditions, the reaction proceeds under mild conditions (80 °C) in air, in the absence of additional ligands, with a catalyst [Cu(I) or Cu(II) species] loading up to 5 mol% and K 2 CO 3 as the base, providing the desired aryloxy derivatives in up to 98% yield. The potential application of the methodology is demonstrated in the valorization of cheap, easily available, and naturally occurring polyols (e.g., glycerol) for the synthesis of some pharmacologically active aryloxypropanediols (Guaiphenesin, Mephenesin and Chlorphenesin) on a 2-gram scale in 70-96% yield. The catalyst, the base, and the DES could easily and successfully be recycled up to seven times with an E-factor as low as 5.76.

In medical and pharmaceutical science phosphonic acids and phosphonates play an important role with regard to their wide application in various drugs as medicines against osteoporosis or antiviral ...

Several examples illustrate the effectiveness of using Deep Eutectic Solvents (DESs) as environmentally responsible reaction media in polar organometallic chemistry and in metal-catalysed and biocatalysed processes in place of conventional, often hazardous volatile organic compounds (VOCs). Apart from the standpoint of ‘greenness’, applications of DESs in the aforementioned fields also reveal novel aspects of reactivity of practical significance, which are worthy of an in-depth mechanistic understanding: (a) metal-mediated organic transformations can be run in DESs competitively with protonolysis, often at room temperature and under air, (b) metal-catalysed reactions proceed efficiently and under milder conditions in DESs than in VOCs, with the catalyst and DES being easily and successfully recycled and (c) biocatalysts often exhibit higher stability, selectivity and performances in DES mixtures than in aqueous solutions, as well as a somewhat intriguing stereoselectivity.

Enantiomerically pure (R)-beta-hydroxy-1,2,3-triazole derivatives, which are important beta-blocker analogues, have been synthesized by exploiting an unusual Prelog enantioselective reduction of aromatic azido ketones by whole cells of a lactic acid bacterium (Weissella cibaria C43-11) and a "click" cycloaddition reaction carried out in deep eutectic solvents, under heterogeneous and aerobic conditions at room temperature.

Electrolytically tunable graphene “building blocks” for reconfigurable and optically transparent microwave surfaces and absorbers have been designed and fabricated by exploiting Deep Eutectic Solvents (DESs). DESs have been first explored as electrolytic and environmentally friendly media for tuning sheet resistance and Fermi level of graphene together with its microwave response (reflection, transmission and absorption). We consider the tunability of the reconfigurable surfaces in terms of transmittance, absorption and reflectance, respectively, over the X and Ku bands when the gate voltage is varied in the −1.4/+1.4 V range. The numerical simulations and experimental measurements also show the ability of the absorber, in the Salisbury screen configuration, to achieve near perfect absorption with a modulation of about 20%. These results could find applications in several technological fields, ranging from electromagnetic pollution to integrated multi-physical regulation systems, thereby helping the advance of the performance of microwave cloaking systems, stealth windows, frequency selective surfaces, modulators and polarizers.

An efficient and selective N-functionalization of amides is first reported via a CuI-catalyzed Goldberg-type C–N coupling reaction between aryl iodides and primary/secondary amides run either in Deep Eutectic Solvents (DESs) or water as sustainable reaction media, under mild and bench-type reaction conditions (absence of protecting atmosphere). Higher activities were observed in an aqueous medium, though the employment of DESs expanded and improved the scope of the reaction to include also aliphatic amides. Additional valuable features of the reported protocol include: (i) the possibility to scale up the reaction without any erosion of the yield/reaction time; (ii) the recyclability of both the catalyst and the eutectic solvent up to 4 consecutive runs; and (iii) the feasibility of the proposed catalytic system for the synthesis of biologically active molecules.

Deep Eutectic Solvents (DESs) are mixtures of Lewis or Brønsted acids and bases showing a melting point much lower than that of the individual components.1 Today, the interest toward DESs is related to their exploitation in several industrial applications2 and to the role that such mixtures appear to have in the transport of macromolecules of diverse polarities inside the plants.3 Ionic liquids share several physicochemical properties (e.g., thermal stability, conductivity, negligible vapor pressures, and easy recycling) with eutectic mixtures and are already exploited as additives in protein crystallization.4 This prompted us to investigate the yet unexplored opportunity to use DESs in protein crystallization. Here, we show, for the first time, that protein molecules are able to crystallize in the presence of DESs.5 Our crystallization experiments have shown that hen-egg white lysozyme crystallizes according to the DES components and the hydration level (Figure 1). Successful crystallization have been achieved by using choline chloride:urea, choline chloride:glycerol, and choline chloride:glutamic acid eutectic mixtures at a 1:2 molar ratio. X-ray diffraction experiments have provided details about the binding sites of DES components on lysozyme protein surface and precise information about the intriguing non-covalent bond network by which protein, DES components and water molecules interact each other. DESs appear to have negligible effects on protein conformation and significantly reduce solvent evaporation from the crystallization drop, a key property to increase the dissolution time of the protein crystals. Moreover, DESs could tune protein solubility because it appears to affect hydration shell of the protein. Our results prove that high-quality protein crystals can be obtained in the presence of DESs and that such crystals can be used to get precise structural information about the interaction between DESs and proteins, which is still lacking in the literature. Moreover, the ability of DESs to protect protein crystals from their rapid dissolution (which has been observed in this work) could be exploited in biotechnological applications involving enzymes in crystalline form.

We report that the nucleophilic acyl substitution reaction of aliphatic and (hetero)aromatic amides by organolithium reagents proceeds quickly (20 s reaction time), efficiently, and chemoselectively with a broad substrate scope in the environmentally responsible cyclopentyl methyl ether, at ambient temperature and under air, to provide ketones in up to 93 % yield with an effective suppression of the notorious over-addition reaction. Detailed DFT calculations and NMR investigations support the experimental results. The described methodology was proven to be amenable to scale-up and recyclability protocols. Contrasting classical procedures carried out under inert atmospheres, this work lays the foundation for a profound paradigm shift of the reactivity of carboxylic acid amides with organolithiums, with ketones being straightforwardly obtained by simply combining the reagents under aerobic conditions and with no need of using previously modified or pre-activated amides, as recommended.

Supramolecular structure and properties of deep eutectic solvents (DESs) are known to be highly affected by the addition of water, and their use as solvents for poorly water-soluble macromolecules is being actively investigated. We report the first experimental investigation of protein crystallization in DESs. Different hydrophilic and hydrophobic eutectic mixtures, hydrated at different levels, have been screened as crystallization media. DESs were added to the solution containing the precipitant and the buffer required to crystallize three test proteins, and we observed that the volume ratio between DES and the corresponding solution is a key parameter for the crystallization process. Successful crystallization was achieved for the hen-egg white lysozyme when using choline chloride:urea, choline chloride:glycerol, and choline chloride:- glutamic acid eutectic mixtures at a 1:2 molar ratio. High-resolution X-ray diffraction experiments disclosed the possibility to study the intriguing supramolecular network of the molecular complexes formed between protein and DES in the presence of water molecules. Individual DES components have been found to systematically occupy specific protein sites populated by solvent-exposed aromatic residues. Weak interactions between DES components, possibly mediated by water molecules, which resulted in being frozen in the ordered solvent surrounding the protein units in the crystal lattice, were reconstructed at atomic resolution. DESs were found to have a negligible effect on the protein conformation and its flexibility in the solid state. On the other hand, DESs greatly reduced solvent evaporation from the crystallization drop, thereby increasing the dissolution time of the protein crystals. Finally, DESs were found to serve as local modulators of the ordered solvent, and this resulted in a significant change of the protein solubility. In addition, we found that protein crystallization was sped up by tuning DES hydration. This enables the employment of these environmentally responsible solvents to improve biotechnological processes at the industrial level.

The Meyer-Schuster rearrangement of propargylic alcohols into α,β-unsaturated carbonyl compounds has been revisited by setting up an atom-economic process catalyzed by a deep eutectic solvent FeCl3·6H2O/glycerol. Isomerizations take place smoothly, at room temperature, under air and with short reaction times. The unique solubilizing properties of the eutectic mixture enabled the use of a substrate concentration up to 1.0 M with the medium being recycled up to ten runs without any loss of catalytic activity.

Directed ortho metalation (DoM) or nucleophilic acyl substitution (SNAc) can be efficiently programmed on the same aromatic carboxylic acid amide, in a choline chloride-based eutectic mixture, by simply switching the nature of the organolithium reagent. Telescoped, one-pot ortho-lithiation/Suzuki–Miyaura cross-couplings have also been demonstrated for the first time in Deep Eutectic Solvents.

The use of a hydrophobic eutectic solvent based on dl-menthol and a naturally occurring acid such as acetic acid has been tested as an eco-friendly electrolyte medium in dye-sensitized solar cells. In the presence of a de-aggregating agent and a representative hydrophobic organic photosensitizer, the corresponding devices displayed relatively good power conversion efficiencies in very thin active layers. In particular, the higher cell photovoltage detected in comparison to devices based on toxic and volatile organic compounds may stem from a more efficient interface interaction, as suggested by electrochemical impedance spectroscopy studies showing greater charge recombination resistance and electron lifetime.