New derivatives from dehydrodieugenol B and its methyl ether displayed high anti-Trypanosoma cruzi activity and cause depolarization of the plasma membrane and collapse the mitochondrial membrane potential.

In the present work, dehydrodieugenol B (1) and its methyl ether (2), isolated from Nectandra leucantha twigs, were used as starting material for the preparation of two new derivatives (1a and 2a) containing an additional methoxycarbonyl unit on allyl side chains. Compounds 1a and 2a demonstrated activity against trypomastigotes (EC50 values of 13.5 and 23.0 µM, respectively) and against intracellular amastigotes (EC50 values of 10.2 and 6.1 µM, respectively). Additionally, compound 2a demonstrated no mammalian cytotoxicity up to 200 µM whereas compound 1a exhibited a CC50 value of 139.8 µM. The mechanism of action studies of compounds 1a and 2a demonstrated a significant depolarization of the plasma membrane potential in trypomastigotes, followed by a mitochondrial membrane potential collapse. Neither calcium level nor reactive oxygen species alterations were observed after a short-time incubation. Considering the potential of compound 2a against T. cruzi and its simple preparation from the natural product 2, isolated from N. leucantha, this compound could be considered a new hit for future drug design studies in Chagas disease.

Diastereoselective hydrogenation of arenes and pyridines using supported ruthenium nanoparticles under mild conditions.

A convenient and practical diastereoselective cis-hydrogenation of multi-substituted pyridines and arenes is reported. Applying a novel heterogeneous ruthenium catalyst, the corresponding piperidines and cyclohexanes are obtained in high yields (typically >80%) with a good functional group tolerance under mild conditions. The robust ruthenium supported catalyst is smoothly prepared and can be reused multiple times without activity loss.

Single-Step Sustainable Production of Hydroxy-Functionalized 2-Imidazolines from Carbohydrates.

Manufacturing valuable N-containing chemicals from biomass is highly desirable yet challenging. Herein, a novel strategy was developed for efficient production of 2-(1-hydroxyethyl)-imidazoline (HI), a high-value and versatile building block for synthesizing a myriad of bioactive targets, directly from carbohydrates under mild reaction conditions. With this strategy, bio-based HI was produced from fructose in one step with as high as 77 C % isolated yield in the presence of ethylenediamine (EDA) and InCl3 at 130 °C. The synergistic functions of EDA and InCl3 were identified for the transformation, wherein EDA promoted the scission of C-C bond of fructose backbone via retro-aldol (R-A) reaction and rapidly trapped in-situ formed reactive carbonyl-containing C3 intermediate for HI formation to avoid undesired side reaction, and InCl3 facilitated the formation of this C3 intermediate and the final 1,2-hydrid shift step.

Iridium-Catalyzed Hydrogenation and Dehydrogenation of N-Heterocycles in Water under Mild Conditions.

An efficient catalytic method is presented for the hydrogenation of N-heterocycles. The iridium-based catalyst operates under mild conditions in water without any co-catalyst or stoichiometric additives. The catalyst also promotes the reverse reaction of dehydrogenation of N-heterocycles, hence displaying appropriate characteristics for a future hydrogen economy based on liquid organic hydrogen carriers (LOHCs).

Base-Free Dehydrogenation of Aqueous and Neat Formic Acid with Iridium(III) Cp*(dipyridylamine) Catalysts.

The selective dehydrogenation of formic acid by iridium(III) Cp*(dipyridylamine) catalysts is reported. The electron-enriched catalyst [IrIII Cp*{(4-dimethylaminopyridin-2-yl-κΝ)(pyridin-2'-yl-κΝ)amine}(OSO3 )] gave the best performances enabling the base free dehydrogenation of aqueous and neat formic acid. In both cases the reaction was selective with no carbon monoxide detectable. The IrIII complex demonstrated latent behavior, which may be of practical utility. Experimental results suggest an outer-sphere interaction with the ligand.

Selective and Efficient Iridium Catalyst for the Reductive Amination of Levulinic Acid into Pyrrolidones.

The catalytic reductive amination of levulinic acid (LA) into pyrrolidones with an iridium catalyst using H2 as hydrogen source is reported. The chemoselective iridium catalyst displayed high efficiency for the synthesis of a variety of N-substituted 5-methyl-2-pyrrolidones and N-arylisoindolinones. N-Substituted 5-methyl-2-pyrrolidone was also evaluated as a biosourced substitute solvent to NMP (N-methylpyrrolidone) in the catalytic arylation of 2-phenylpyridine.

Ethenolysis: A Green Catalytic Tool to Cleave Carbon-Carbon Double Bonds.

Remarkable innovations have been made in the field of olefin metathesis due to the design and preparation of new catalysts. Ethenolysis, which is cross-metathesis with ethylene, represents one catalytic transformation that has been used with the purpose of cleaving internal carbon-carbon double bonds. The objectives were either the ring opening of cyclic olefins to produce dienes or the shortening of unsaturated hydrocarbon chains to degrade polymers or generate valuable shorter terminal olefins in a controlled manner. This Review summarizes several aspects of this reaction: the catalysts, their degradation in the presence of ethylene, some parameters driving their productivity, the side reactions, and the applications of ethenolysis in organic synthesis and in potential industrial applications.

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks.

The cross metathesis of 1,2-epoxy-5-hexene (1) with methyl acrylate and acrylonitrile was investigated as an entry to the synthesis of polyfunctional compounds. The resulting cross metathesis products were hydrogenated in a tandem fashion employing the residual ruthenium from the metathesis step as the hydrogenation catalyst. Interestingly, the epoxide ring remained unreactive toward this hydrogenation method. The saturated compound resulting from the cross metathesis of 1 with methyl acrylate was transformed by means of nucleophilic ring-opening of the epoxide to furnish a diol, an alkoxy alcohol and an amino alcohol in high yields.

Interest of the Precatalyst Design for Olefin Metathesis Operating in a Discontinuous Nanofiltration Membrane Reactor.

This study aimed at evaluating the impact of the structure of several new olefin metathesis homogeneous catalysts on the performances of a membrane reactor running in a discontinuous mode and equipped with a nanofiltration membrane that was stable in toluene. A set of tailor-made ruthenium-based precatalysts were prepared with a first objective of enhancing the retention of the precatalyst, that is the stable source of the active catalyst, by organic solvent nanofiltration using a commercial polyimide membrane (Starmem 122). These prototype precatalysts were designed taking into account both the molecular weight and the physicochemical characteristics allowing up to 99.6 % retention of the precatalyst in toluene. The new precatalysts were then engaged in a model ring-closing metathesis reaction in the membrane reactor. Results, expressed as the precatalyst apparent turnover number, showed significant differences according to the selected precatalyst, underlining that the membrane reactor advantages and limitations were closely linked to the intrinsic activity of the catalyst. In addition to the retention of the precatalyst by the membrane, a major parameter was the percentage of the precatalyst really activated during the first load of the substrate since that controls the residual amount of precatalyst to be engaged in the following reaction cycle. The main consequence was the proposal of different running modes consisting of a cascade of synthesis in batch mode and separation by the membrane or a membrane reactor process.

Methyl ricinoleate as platform chemical for simultaneous production of fine chemicals and polymer precursors.

The modification of methyl ricinoleate by etherification of the hydroxyl group was accomplished by using a nonclassical ruthenium-catalyzed allylation reaction and also by esterification. Methyl ricinoleate derivatives were engaged in ring-closing metathesis (RCM) reactions leading to biosourced 3,6-dihydropyran and α,ß-unsaturated lactone derivatives with concomitant production of polymer precursors. Sequential RCM/hydrogenation and RCM/cross-metathesis were also implemented as a straightforward method for the synthesis of tetrahydropyran and lactone derivatives as well as valuable monomers (i.e., polyamide precursors).

New ruthenium metathesis catalysts with chelating indenylidene ligands: synthesis, characterization and reactivity.

Six new ruthenium complexes bearing a bidentate (κ(2)O,C)-isopropoxy-indenylidene and PPh(3) or PCy(3) ligands have been synthesized and characterized by (1)H, (13)C NMR spectroscopy and X-ray crystallography. Some of these complexes were synthesized in dimethyl carbonate, a green solvent that was recently shown to be suitable for several catalytic transformations including olefin metathesis. The thermal stability and catalytic efficiency of the PCy(3)-containing complexes have been evaluated in a series of test reactions.

Ene-yne cross-metathesis with ruthenium carbene catalysts.

Conjugated 1,3-dienes are important building blocks in organic and polymer chemistry. Enyne metathesis is a powerful catalytic reaction to access such structural domains. Recent advances and developments in ene-yne cross-metathesis (EYCM) leading to various compounds of interest and their intermediates, that can directly be transformed in tandem procedures, are reviewed in this article. In addition, the use of bio-resourced olefinic substrates is presented.

Ruthenium-indenylidene olefin metathesis catalyst with enhanced thermal stability.

Two new ruthenium complexes bearing a bidentate (κ(2)O,C)-isopropoxy-indenylidene ligand and a PPh(3) (9) or PCy(3) (10, Cy=cyclohexyl) ligand have been synthesized and fully characterized by (1)H and (13)C NMR spectroscopy and X-ray crystallography. Complex 10 displays a very high thermal stability with a half life of six days at 110 °C in [D(8)]toluene. Complex 10 was evaluated in various ring-closing metathesis reactions and ring-opening metathesis polymerization of dicyclopentadiene, in which it showed a latent behavior with low activity at room temperature and high activity upon thermal activation.

Improving sustainability in ene-yne cross-metathesis for transformation of unsaturated fatty esters.

Ruthenium-catalyzed ene-yne cross-metathesis is performed with stoichiometric proportions of terminal olefins and alkynes. This is made possible by the continuous addition of the alkyne to the reaction mixture. The protocol allows the ene-yne cross-metathesis reaction to be carried out with long-chain terminal olefins and in a one-pot fashion with internal olefins after shortening by ethenolysis. The efficient conversion of renewable unsaturated fatty esters from bioresources into valuable conjugated 1,3-dienes of interest for further transformations is performed using this technique under mild conditions in dimethyl carbonate; an ecofriendly solvent.

Direct amination of aryl halides with ammonia.

The traditional homogeneous access to aromatic amine derivatives is a nucleophilic aromatic substitution of the corresponding aryl halides. The halogen atom is usually relatively inert to amination reaction unless it is activated by the presence of electron withdrawing groups. Consequently, there has been particular emphasis over the past decade on the synthesis of metal complexes that are active catalysts for the preparation of aromatic amines. This tutorial review focuses on the use of metal-based complexes for the direct amination of aryl halides with ammonia.

Efficient synthesis of aminopyridine derivatives by copper catalyzed amination reactions.

A copper(i) catalyzed amination reaction utilizing aqueous ammonia and operating under mild conditions is presented. This method was employed for the efficient synthesis of various aminopyridine derivatives bearing electron withdrawing and electron donating groups.

A direct route to bifunctional aldehyde derivatives via self- and cross-metathesis of unsaturated aldehydes.

Ruthenium-catalyzed self- and cross-metathesis, with acrolein, acrylonitrile, acrylic acid and methylacrylate, of the bioresource undecylenic aldehyde leads to a variety of unsaturated omega-functional aldehydes. Tandem olefin metathesis/hydrogenation catalytic reactions afford saturated C(20) and C(12) diols in good yields.

Recovery of enlarged olefin metathesis catalysts by nanofiltration in an eco-friendly solvent.

This study was aimed at integrating a green separation process without phase change, namely nanofiltration, with olefin metathesis to recover the homogeneous catalyst. As the commercially available Hoveyda II catalyst was not sufficiently retained by the membrane, a set of homogeneous ruthenium-based catalysts were prepared to enhance the recovery of the catalyst by solvent-resistant commercial membranes made of polyimide (Starmem 228). The molecular weights of the catalysts were gradually increased from 627 to 2195 g mol(-1), and recovery was found to increase from around 70 % to 90 % both in toluene and dimethyl carbonate. The most retained catalyst was then engaged in a series of model ring-closing metathesis reactions associated to a final nanofiltration step to recover and recycle the catalyst. Up to five cycles could be performed before a deterioration in the performance of the process was observed.