RESUMEN

An enhanced, sustainable, and efficient method for synthesizing tacrine, achieving a 98% yield, has been developed by replacing volatile organic compounds with more eco-friendly solvents such as deep eutectic solvent (DESs). The optimized protocol scales easily to 3 g of substrate without yield loss and extends successfully to tacrine derivatives with reduced hepatotoxicity. Particularly notable is the synthesis of novel triazole-based derivatives, yielding 90-95%, by integrating an in situ preparation of aryl azides in DESs with N-propargyl-substituted tacrine derivatives. Quantitative metrics validate the green aspects of the reported drug development processes.

RESUMEN

The highly efficient biodeoximation of aromatic ketoximes, promoted by the enzymatic oxidative system laccase/TEMPO/O2, has been successfully assembled with the fast and chemoselective addition of highly-polar s-block organometallic reagents (RLi/RMgX) en route to highly-substituted tertiary alcohols. By using this hybrid one-pot tandem protocol, tertiary alcohols have been selectively synthesized in good yields and under mild and bench-type reaction conditions (room temperature, the absence of a protecting atmosphere and aqueous media, which are non-typical conditions for polar organometallic reagents). The overall hybrid one-pot tandem transformation amalgamates two distant organic synthetic tools (RLi/RMgX reagents and enzymes) without the need for any tedious and energy/time-consuming intermediate isolation/purification steps.

RESUMEN

An efficient, selective and sustainable protocol was developed for the CuCl2 /TEMPO/TMEDA-catalyzed aerobic oxidation of activated alcohols to the corresponding carbonyl compounds using water or the environmentally friendly low melting mixture (LMM) d-fructose-urea as the reaction medium. Such oxidation reactions proceed under mild (room temperature or 40 °C) and aerobic conditions, with the carbonyl derivatives isolated in up to 98 % yield and within 4 h reaction time when using the above-mentioned LMM. The potential application of this methodology is demonstrated by setting up useful telescoped, one-pot two-step hybrid transformations for the direct conversion of primary alcohols either into secondary alcohols or into valuable nitroalkenes, by combining oxidation processes with nucleophilic additions promoted by highly polarized organometallic compounds (Grignard and organolithium reagents) or with nitroaldol (Henry) reactions, respectively.

Asunto(s)

RESUMEN

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%).

RESUMEN

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.

RESUMEN

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.

Asunto(s)

RESUMEN

The Meyer-Schuster rearrangement of propargylic alcohols into α,ß-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.

RESUMEN

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).

RESUMEN

Highly polarized lithium phosphides (LiPR2 ) were synthesized, for the first time, in deep eutectic solvents as sustainable reaction media, at room temperature and in the absence of protecting atmosphere, through direct deprotonation of both aliphatic and aromatic secondary phosphines (HPR2 ) by n-BuLi. The subsequent addition of in-situ generated LiPR2 to aldehydes or epoxides proceeded quickly and chemoselectively, thereby allowing the straightforward access to the corresponding α- or ß-hydroxy phosphine oxides, respectively, under air and at room temperature (bench conditions), which are traditionally considered as textbook-prohibited conditions in the field of polar organometallic chemistry of s-block elements.

RESUMEN

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).

RESUMEN

It has always been a firm conviction of the scientific community that the employment of both anhydrous conditions and water-free reaction media is required for the successful handling of organometallic compounds with highly polarised metal-carbon bonds. Herein, we describe how, under heterogeneous conditions, Grignard and organolithium reagents can smoothly undergo nucleophilic additions to γ-chloroketones, on the way to 2,2-disubstituted tetrahydrofurans, "on water", competitively with protonolysis, under batch conditions, at room temperature and under air. The reactivity of the above organometallic reagents has also been investigated in conventional anhydrous organic solvents and in bio-based eutectic and low melting mixtures for comparison. The scope and limitations of this kind of reaction are discussed.