Palladium-Catalyzed Tsuji-Trost-Type Reaction of 3-Indolylmethylacetates with O, and S Soft Nucleophiles.

The chemical valorization of widespread molecules in renewable sources is a field of research widely investigated in the last decades. In this context, we envisaged that indole-3-carbinol, present in different plants, could be a readily available building block for the synthesis of various classes of indoles through a palladium-catalyzed Tsuji-Trost-type reaction with O and S soft nucleophiles. The regiochemical outcome of this high-yielding functionalization shows that the nucleophilic substitution occurs only at the benzylic position.

Experimental Results and Mechanistic Insights on the Reactions of Indolylmethyl Acetates with Soft Carbon Pronucleophiles.

The palladium-catalyzed reaction of -protected 2-indolylmethyl acetates with soft carbon pronucleophiles is described. Besides the formation of the expected coupling reaction at the C1' position, unprecedented attack at the C3 position of the plausible η-indolyl-palladium intermediate has been observed, and the selectivity control C1'/C3 seems to depend on the nature of the protecting group and ligand. The reactivity of 3-indolylmethyl acetates has also been also investigated.

Valorisation of Side Stream Products through Green Approaches: The Rapeseed Meal Case.

Rapeseed meal (RSM) is a by-product of rapeseed oil extraction and is a rich source of bioactive compounds, including proteins and antioxidants. This study compared two methods for extracting antioxidants from RSM: conventional ethanol Soxhlet extraction and supercritical CO extraction. These procedures were applied to both native RSM and RSM after protein removal to evaluate their bio-compound composition and potential applications.

Synthesis of Functionalized 3-pyrrolo-[1,2,3-] Quinoxalines via Gold-Catalyzed Intramolecular Hydroamination of Alkynes.

A gold-catalyzed protocol to obtain functionalized 3-pyrrolo [1,2,3-] quinoxalines from suitable substituted indoles has been proposed. The mild reaction conditions were revealed to be compatible with different functional groups, including halogen, alkoxyl, cyano, ketone, and ester, allowing the isolation of title compounds with yields from good to high. A reaction mechanism has been proposed, and theoretical calculations have been provided to rationalize the final step of the hypothesized reaction mechanism.

Direct Regioselective Hydro(hetero)arylation/Cyclocondensation Reactions of β-(2-Aminophenyl)-α,β-ynones by Means of Transition-Metal Catalysis/Brønsted Acid Synergism: Experimental Results and Computational Insights.

Experimental results and computational insights explain the key role of transition-metal catalysis/Brønsted acid synergism in the achievement of the sequential regioselective direct heteroarylation/cyclocondensation reactions of β-(2-aminophenyl)-α,β-ynones with a variety of electron-rich aromatic heterocyclic/arenes to afford quinoline-(hetero)aromatic hybrids. The first approach to the synthesis of 4-(1-pyrrol-2-yl)quinolines is described. The effectiveness of various transition metals is compared.

Synthesis of 3-substituted 2,3-dihydropyrazino[1,2-]indol-4(1)-ones by sequential reactions of 2-indolylmethyl acetates with α-amino acids.

The synthesis of 2,3-dihydropyrazino[1,2-]indol-4(1)-ones from the sequential reaction of amino acid methyl esters with readily available indole-2-ylmethyl acetates is described. The reaction proceeds under basic conditions of highly unstable and reactive 2-alkylideneindolenines followed by Michael-type addition of α-amino acid methyl esters/intramolecular cyclization.

Highly Efficient and Mild Gold (I) Catalyzed Synthesis of 3,8-Diarylidene-2,7-dioxaspiro[4.4]nonane-1,6-diones.

The gold-catalyzed cyclization of 2,2-bis(3-arylprop-2-yn1-yl)malonic acid has been proposed as an efficient approach to substituted 3,8-dibenzyl-2,7-dioxaspiro[4.4]nonane-1,6-diones. The reaction proceeds smoothly in mild reaction conditions to give the desired products in quantitative yields in the presence of variously substituted starting materials.

One-pot synthesis of dihydroquinolones by sequential reactions of -aminobenzyl alcohol derivatives with Meldrum's acids.

The functionalized 3,4-dihydroquinolin-2-one nucleus has been assembled in good to high yields through the sequential reaction of readily available -Ts--aminobenzyl alcohols with 5-substituted Meldrum's acid derivatives under mild basic conditions. Highly diastereoselective synthesis of 3-substituted-4-phenyl-1-tosyl-3,4-dihydroquinolin-2(1)-ones was accomplished from -(2-(hydroxy(phenyl)methyl)phenyl)-4-methylbenzenesulfonamide under the same reaction conditions. Regarding the reaction mechanism, we hypothesized that the formation of dihydroquinolones proceeds through the generation of aza--QMs followed by conjugate addition of enolate/cyclization/elimination of acetone and CO.

Valorization of By-Products from Biofuel Biorefineries: Extraction and Purification of Bioactive Molecules from Post-Fermentation Corn Oil.

The aim of this work was to develop innovative and sustainable extraction, concentration, and purification technologies aimed to recover target substances from corn oil, obtained as side stream product of biomass refineries. Residues of bioactive compounds such as carotenoids, phytosterols, tocopherols, and polyphenols could be extracted from this matrix and applied as ingredients for food and feeds, nutraceuticals, pharmaceuticals, and cosmetic products. These molecules are well known for their antioxidant and antiradical capacity, besides other specific biological activities, generically involved in the prevention of chronic and degenerative diseases.

Synthesis of 4-Substituted-1,2-Dihydroquinolines by Means of Gold-Catalyzed Intramolecular Hydroarylation Reaction of -Ethoxycarbonyl--Propargylanilines.

An alternative Au(I)-catalyzed synthetic route to functionalized 1,2-dihydroquinolines is reported. This novel approach is based on the use of -ethoxycarbonyl protected--propargylanilines as building blocks that rapidly undergo the IMHA reaction affording the 6- cyclization product in good to high yields. In the presence of -ethoxycarbonyl--propargyl-substituted anilines, the regiodivergent cyclization at the -/-position is achieved by the means of catalyst fine tuning.

Sequential condensation/biannulation reactions of β-(2-aminophenyl)-α,β-ynones with 1,3-dicarbonyls.

A divergent domino condensation/biannulation reaction of β-(2-aminophenyl) α,β-ynones with 1,3-dicarbonyls to construct a polycyclic 4H-pyrano[3,4-c]quinoline core has been developed. The p-TsOH·H2O catalyzed reaction of β-(2-aminophenyl) α,β-ynones with β-ketoesters in ethanol proceeds with good to excellent yields to provide a simple and effective method for the synthesis of functionalized 4H-pyrano[3,4-c]quinolinones. Further elaboration of these latter derivatives with an excess of 20% NH4OH in EtOH at 50 °C helps achieve the synthesis of the perlodinine analogues benzo[c][2,7]naphthyridin-4(3H)-one derivatives in high yields.

Palladium-catalyzed Tsuji-Trost-type reaction of benzofuran-2-ylmethyl acetates with nucleophiles.

The palladium-catalyzed benzylic-like nucleophilic substitution of benzofuran-2-ylmethyl acetate with N, S, O and C soft nucleophiles has been investigated. The success of the reaction is dramatically influenced by the choice of catalytic system: with nitrogen based nucleophiles the reaction works well with Pd(dba)/dppf, while with sulfur, oxygen and carbo-nucleophiles [Pd(η-CH)Cl]/XPhos is more efficient. The regiochemical outcome shows that the nucleophilic substitution occurs only on the benzylic position of the η-(benzofuryl)methyl complex.

Synthesis of functionalised 2,3-dihydroquinolin-4(1)-ones quinoline or -alkenylindole derivatives through sequential reactions of 2-alkynylanilines with ketones.

This study describes diversity-oriented synthesis of 2,2,3-substituted-2,3-dihydroquinolin-4(1H)-ones vs. functionalised quinoline or N-alkenylindole derivatives through Brønsted acid mediated or Lewis acid catalyzed sequential reactions of 2-alkynylanilines with ketones. In particular, a series of challenging quinolin-4-one derivatives are prepared with good functional group tolerance in an atom-economical fashion by using p-toluenesulfonic acid monohydrate as a promoter of the reaction of ketones with 2-alkynylanilines in EtOH at reflux, while the same starting materials give the corresponding 4-substituted quinolines in toluene at 110 °C both in the presence of p-toluenesulfonic acid monohydrate as the promoter and FeCl3 as the catalyst.

Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections.

Antibiotic resistance is now considered a worldwide problem that puts public health at risk. The onset of bacterial strains resistant to conventional antibiotics and the scarcity of new drugs have prompted scientific research to re-evaluate natural products as molecules with high biological and chemical potential. A class of natural compounds of significant importance is represented by alkaloids derived from higher plants.

Synthesis of pyrano[2,3-f]chromen-2-ones vs. pyrano[3,2-g]chromen-2-ones through site controlled gold-catalyzed annulations.

Regioselective access to 10-substituted-2H,8H-pyrano[2,3-f]chromen-2-ones through the gold-catalyzed intramolecular hydroarylation of readily available 7-(prop-2-yn-1-yloxy)-2H-chromen-2-one derivatives at their C-8 congested position was investigated by tuning the electronic and steric properties of the ligand on the gold complex. On the other hand, the combination of the JohnPhosAu(MeCN)SbF6 catalyzed intramolecular hydroarylation of 8-iodo-7-(prop-2-yn-1-yloxy)-2H-chromen-2-one derivatives followed by selective palladium/formate C-I reduction allows for the exclusive formation of 2H,8H-pyrano[3,2-g]chromen-2-one regioisomers. The development of these two protocols provides versatile synthetic tools required for exploring the biological activities of these new pyranocoumarin derivatives.

Stereo- and regioselective gold(i)-catalyzed hydroamination of 2-(arylethynyl)pyridines with anilines.

The gold-catalyzed hydroamination of 2-(arylethynyl)pyridines with anilines affords stereoselectively Z-enamine products with excellent regioselectivity. The reaction proceeds with moderate to excellent yields and accommodates a diverse range of functional groups on alkynes (ether, bromo, trifluoromethyl, acetyl, and carbomethoxy) and anilines (ether, bromo, chloro, and carbethoxy). The stereochemistry of the obtained enamines is complementary to that reported in previous studies.

Synthesis of indolo[1,2-]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with ,-dimethylformamide dimethyl acetal.

An efficient strategy for the synthesis of 6-unsubstituted indolo[1,2-]quinazolines is described. The Pd-catalyzed reaction of -(-aminophenylethynyl) trifluoroacetanilides with Ar-B(OH) afforded 2-(-aminophenyl)-3-arylindoles, that were converted to 12-arylindolo[1,2-]quinazolines by adding dimethylformamide dimethyl acetal (DMFDMA) to the reaction mixture after extractive work-up. This reaction outcome is different from the previously reported Pd-catalyzed sequential reaction of the same substrates with Ar-I, Ar-Br and ArNBF, that afforded 12-arylindolo[1,2-]quinazolin-6(5)-ones.

Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2-Substituted 3-Aroylquinolin-4(1H)-ones as Inhibitors of the Hedgehog Signaling Pathway.

2-Substituted 3-aroylquinolin-4(1H)-ones, prepared through a palladium-catalyzed carbonylative cyclization of N-(2-iodoaryl)enaminones, proved to inhibit efficiently the Hedgehog pathway through direct antagonism of the wild-type and drug-resistant form of the Smoothened receptor. Notably, these compounds repressed the Hh-dependent growth events and the proliferation of tumor cells with aberrant activation of the Hh pathway, which plays a crucial role in development and tumorigenesis.

Construction of the 1,5-Benzodiazepine Skeleton from o-Phenylendiamine and Propargylic Alcohols via a Domino Gold-Catalyzed Hydroamination/Cyclization Process.

The gold-catalyzed reaction of o-phenylendiamine with propargylic alcohols affords 1,5-benzodiazepines bearing different substituents on the 2 and 4 positions. The method allows even for the selective preparation of 4-substituted 1,5-benzodiazepine derivatives.

Pd- and Rh-Catalyzed Hydroarylation of γ-(2-Methoxycarbonylphenyl)propargylic Alcohols: Approaches to 4- or 5-Substituted Seven-Membered Benzolactones and 3,3-Disubstituted Phthalides.

A study of the palladium-catalyzed hydroarylation/hydrovinylation reaction of γ-(2-methoxycarbonylphenyl)propargylic alcohols with aryl iodides/vinyl triflates and of the rhodium-catalyzed one with organoboron derivatives is described. The opposite regiochemical outcome of the two processes allows an easy selective approach to 5- or 4-substituted benzoxepin-1(3H)-ones by combining the hydroarylative/hydrovinylative step with cyclocondensation between -OH and -COOMe groups in the intermediate γ,γ-disubstituted or β,γ-disubstituted allylic alcohols. A one-flask procedure to give benzo[c]oxepin-1(3H)-ones directly from the starting alkyne has been also developed.

[Alcohol and work. Consensus Document of the La.R.A. (Workers representing a risk for others) group].

Aim: Current Italian legislation obliges employers to prevent workers who are occupationally at risk or who perform jobs that may be hazardous for the safety or health of third parties from consuming alcohol. The LaRA Group undertook to assess whether the law fully safeguards the health and safety of both workers and third parties, without impinging upon the civil rights of workers.

Method: A written document expressing agreement was produced following discussions between doctors, lawyers, bioethicists and social partners.

Palladium-catalyzed synthesis of 2-(aminomethyl)indoles from 3-(o-trifluoroacetamidoaryl)-1-propargylic alcohols and amines.

A novel palladium-catalyzed approach to 2-(aminomethyl)indoles from 3-(o-trifluoroacetamidoaryl)-1-propargylic alcohols and amines has been developed.

[Accidents at work and occupational diseases trend in agriculture insurance management. The contribution of INAIL data's for the knowledge of a worrying phenomenon].

The author's describe accidents at work and occupational diseases outcome's measure in Agricolture insurance management acquired through statistical approach based on data processing provided by INAIL Bank data. Accident's incidence in Agricolture is compared to main insurance managements, using frequency index of accidents appearance selected on line of work and type of consequence. Concerning occupational diseases the authors describes the complaints and compensation with the comparison referring the analysis to statistical general data.

Palladium-catalyzed cascade reactions of 1-(3-arylprop-2-ynyloxy)-2-bromo benzene derivatives with organoboron compounds.

Applications of the cascade cyclocarbopalladation reaction followed by Suzuki-Miyaura coupling reactions of the readily available aryl-substituted propargylic aryl ethers with arylboronic acid and potassium trans-β-styryltrifluoroborate accomplish a new versatile entry in the synthesis of benzofuran derivatives. Notably, a new approach to the challenging synthesis of C3 functionalized 2-unsubstituted benzofurans has been developed by a cyclocarbopalladation/cross-coupling/aromatization process.

[The accident at work and the occupational diseases in the construction industry: the experience of Inail].

The authors analyze the budget accident at work and occupational diseases in the construction industry through the data banks Inail. This analysis is carried out by comparing the data for this sector of economic activity (classification of economic activities ATECO 2002) with those general with particular attention to how an event, occurrence, mortality, by plotting the trends of this phenomenon than in previous years. It also analyzes the phenomenon of the complaints of occupational diseases with the comparison with the general data as well as with the analysis of the most frequent types of occupational diseases in this sector in the last two years.