Dearomatizzazione organocatalitica regio- ed enantioselettiva di sali di piridinio attivati

In this work, we present the first regio- and enantioselective organocatalytic nucleophilic dearomatization of activated N-alkyl pyridinium salts. In particular, N-benzyl pyridinium bromides bearing electron-withdrawing substituents at the C3 position of the pyridine ring were chosen as substrates. These compounds were easily obtained through an alkylation reaction between benzyl bromides and the corresponding 3-substituted pyridines. Then, a wide range of nucleophiles and organocatalysts was tested, providing the best results when indole, a thiourea derived from quinidine and 1-benzyl-3-nitropyridinum bromide were employed as the nucleophile, the catalyst and the pyridinium salt, respectively. Subsequently, the reaction conditions were optimised evaluating different bases, solvents, N-benzylic protecting groups, molar concentrations and temperatures. With the optimized condition in hand, the scope of the reaction with different substituted indoles was explored, affording the corresponding 1,4-dihydropyridines in good yields, regio- and enantio-selectivities. In addition, several experiments were carried out in order to understand the mechanism of the reaction, showing an unusual pathway involving a covalently bound intermediate formed by addition of the catalyst to the pyridine unit.

Gold Phosphonates as Transfer Agents in Palladium Catalyzed Hirao Reactions

Through a cross-coupling reaction, aryl phosphonates are produced in high yields when the corresponding aryl bromides are reacted with a gold phosphorylating agent in the presence of a palladium catalyst and an appropriate ligand. To the best of our knowledge, this transformation is the first example involving the transfer of a phosphonate functional group from a gold complex to palladium that has been reported. Throughout the investigation, three gold phosphorylating agents were screened for activity towards the phosphorylation of aryl bromides. Aryl bromides with electrondonating and electron-withdrawing groups were successfully employed in the crosscoupling reactions. All cross-coupling reactions were carried out in THF at room temperature (25ºC) or in a microwave reactor (CEM Discover) at 60ºC for 30 or 60 minutes. The effects of changing reaction parameters such as time, temperature, catalyst and free ligand loading have been investigated. All aryl bromide substrates tested in the cross-coupling reactions produced phosphorylated products.

Odorless Preparation Of Thioglycosides And Thio Michael Adducts Of Carbohydrate Derivatives

A generalized, odorless, one-pot methodology has been developed for the preparation of 1,2-trans-thioglycosides and thio-Michael addition products of carbohydrate derivatives through triphenyl phosphine mediated cleavage of disulfides and reaction of the thiolate formed in situ with glycosyl bromides and glycosyl conjugated alkenes.

Enhancing the catalytic repertoire of nucleic acids: a systematic study of linker length and rigidity

The incorporation of potentially catalytic groups in DNA is of interest for the in vitro selection of novel deoxyribozymes. A series of 10 C5-modified analogues of 2′-deoxyuridine triphosphate have been synthesised that possess side chains of differing flexibility and bearing a primary amino or imidazole functionality. For each series of nucleotide analogues differing degrees of flexibility of the C5 side chain was achieved through the use of alkynyl, alkenyl and alkyl moieties. The imidazole function was conjugated to these C5-amino-modified nucleotides using either imidazole 4-acetic acid or imidazole 4-acrylic acid (urocanic acid). The substrate properties of the nucleotides (fully replacing dTTP) with Taq polymerase during PCR have been investigated in order to evaluate their potential applications for in vitro selection experiments. 5-(3-Aminopropynyl)dUTP and 5-(E-3-aminopropenyl)dUTP and their imidazole 4-acetic acid- and urocanic acid-modified conjugates were found to be substrates. In contrast, C5-amino-modified dUTPs with alkane or Z-alkene linkers and their corresponding conjugates were not substrates. The incorporation of these analogues during PCR has been confirmed by inhibition of restriction enzyme digestion using XbaI and by mass spectrometry of the PCR products.

Designing surfaces that kill bacteria on contact

Poly(4-vinyl-N-alkylpyridinium bromide) was covalently attached to glass slides to create a surface that kills airborne bacteria on contact. The antibacterial properties were assessed by spraying aqueous suspensions of bacterial cells on the surface, followed by air drying and counting the number of cells remaining viable (i.e., capable of growing colonies). Amino glass slides were acylated with acryloyl chloride, copolymerized with 4-vinylpyridine, and N-alkylated with different alkyl bromides (from propyl to hexadecyl). The resultant surfaces, depending on the alkyl group, were able to kill up to 94 ± 4% of Staphylococcus aureus cells sprayed on them. A surface alternatively created by attaching poly(4-vinylpyridine) to a glass slide and alkylating it with hexyl bromide killed 94 ± 3% of the deposited S. aureus cells. On surfaces modified with N-hexylated poly(4-vinylpyridine), the numbers of viable cells of another Gram-positive bacterium, Staphylococcus epidermidis, as well as of the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli, dropped more than 100-fold compared with the original amino glass. In contrast, the number of viable bacterial cells did not decline significantly after spraying on such common materials as ceramics, plastics, metals, and wood.

Enantioselective alkylation of β-keto esters promoted by dimeric Cinchona-derived ammonium salts as recoverable organocatalysts

Dimeric anthracenyldimethyl-derived Cinchona ammonium salts are used as chiral organocatalysts in 5 mol% for the phase-transfer enantioselective alkylation reaction of 2-alkoxycarbonyl-1-indanones with activated bromides. The corresponding adducts bearing a new all-carbon quaternary center are obtained usually in high yield and with moderate and opposite enantioselectivity (up to 55%) when using ammonium salts derived from quinidine and its pseudoenantiomer quinine as organocatalysts. These catalysts can be almost quantitatively recovered by precipitation in ether and reused.

NHC-Ligand Effectiveness in the Fluorine-Free Hiyama Reaction of Aryl Halides

1-Benzyl-3-(2-hydroxy-2-phenylethyl)imidazolium chloride (5), which is a precursor of an N-heterocyclic carbene ligand, in combination with palladium acetate, has been employed as an effective catalyst for the fluorine-free Hiyama reaction. A systematic study of the catalytic mixture, by a 32 factorial design, has revealed that both the amount of palladium and the Pd/NHC precursor ratio are important factors for obtaining good yields of the coupling products, indicating an interaction between them. The best catalytic system involves mixing 0.1 mol-% palladium acetate in a 1:5 ratio (Pd/salt 5), which allows the effective coupling of a range of aryl bromides and chlorides with trimethoxy(phenyl)silane. The Hiyama reactions are carried out in NaOH solution (50 % H2O w/w), at 120 °C under microwave irradiation during 60 min.

TGA/FTIR study of tobacco and glycerol–tobacco mixtures

In this work, the evolution with temperature of the qualitative composition of the gases evolved in the pyrolysis of glycerol, tobacco and tobacco–glycerol mixtures has been studied. The pathways for different types of compounds (i.e., water, CO, CO2, carbonylic compounds, alkenyl or alkyl groups containing compounds, alcohols and phenols and aromatic compounds) have been established, and their relationship with the different reaction steps involved in the pyrolysis process have been suggested. The comparison among the behavior observed in the pyrolysis of tobacco, glycerol and a mixture glycerol–tobacco has permitted us to suggest possible interactions between tobacco and glycerol affecting the composition of the gases evolved.

Palladium nanoparticles supported on graphene and reduced graphene oxide as efficient recyclable catalyst for the Suzuki–Miyaura reaction of potassium aryltrifluoroborates

Palladium nanoparticles supported on graphene platelets have been efficiently used as catalyst in the Suzuki–Miyaura coupling between aryl bromides and potassium aryltrifluoroborates using 0.1 mol% of Pd and potassium carbonate as base in MeOH/H2O as solvent at 80 °C. The reaction can be performed using conventional and microwave heating showing the catalyst high reusability, particularly with microwaves, where lower aggregation of Pd nanoparticles has been observed. A dissolution/re-deposition catalytic mechanism is proposed, based on the fact that palladium leaching to the solution is detected under microwave irradiation.

1,2-Functionalized Imidazoles as Palladium Ligands: An Efficient and Robust Catalytic System for the Fluorine-Free Hiyama Reaction

A variety of hydroxy- and amino-functionalized imidazoles were prepared from 1-methyl- and 1-(diethoxymethyl)imidazole by means of isoprene-mediated lithiation followed by reaction with an electrophile. These compounds in combination with palladium acetate were screened as catalyst systems for the Hiyama reaction under fluorine-free conditions using microwave irradiation. The systematic study of the catalytic system showed 1-methyl-2-aminoalkylimidazole derivative L1 to be the best ligand, which was employed under solvent-free conditions with a 1:2 Pd/ligand ratio and TBAB (20 mol-%) as additive. The study has revealed an interaction between the Pd/ligand ratio and the amount of TBAB. The established catalytic system presented a certain degree of robustness, and it has been successfully employed in the coupling of a range of aryl bromides and chlorides with different aryl siloxanes. Furthermore, both reagents were employed in an equimolecular amount, without an excess of organosilane.

Biscarboxy-Functionalized Imidazole and Palladium as Highly Active Catalytic System in Protic Solvents: Methanol and Water

The coupling reaction between aryl bromides and boron reagents is efficiently catalyzed by an in situ generated palladium complex obtained from palladium(II) acetate (0.1 mol%) and 1,3-bis(carboxymethyl)imidazole (0.2 mol%). The catalytic system is very active in protic solvents, especially in methanol. Biaryl derivatives have been prepared in good isolated yields (up to >99%), and additionally styrene and stilbene derivatives have also been prepared by means of this protocol.

Magnetic nanoparticles supported oxime palladacycle as a highly efficient and separable catalyst for room temperature Suzuki–Miyaura coupling reaction in aqueous media

A novel magnetic nanoparticle-supported oxime palladacycle catalyst was successfully prepared and characterized. The magnetically recoverable catalyst was evaluated in the room temperature Suzuki–Miyaura cross-coupling reaction of aryl iodides and bromides in aqueous media. The catalyst was shown to be highly active under phosphine-free and low Pd loading (0.3 mol%) conditions. The catalyst could be easily separated from the reaction mixture using an external magnet and reused for six consecutive runs without significant loss of activity.

Silica Microparticles Supported Gold and Copper Ferrite Nanoparticles: A Magnetically Recyclable Bimetallic Catalyst for Sonogashira Reaction

Novel silica supported gold and copper ferrite nanoparticles (NPs) have been synthesized, characterized and used as a separable dual catalyst in Sonogashira type reaction. These Au.CuFe2O4@Silica NPs show a high efficiency as catalyst in the alkynylation not only of aryl iodides but also aryl bromides. By using only 0.5 mol% loading and t-BuOK as base in N,N-dimethylacetamide as solvent, aryl iodides react at 115 ºC in 1 d, whereas for aryl bromides the cross-coupling takes place at 130 ºC in 2 d. The catalyst can be successfully recycled using an external magnet for four consecutive runs.

Nutrient partitioning during treatment of tuberculosis: gain in body fat mass but not in protein mass

Background: Tuberculosis is an important cause of wasting. The functional consequences of wasting and recovery may depend on the distribution of lost and gained nutrient stores between protein and fat masses. Objective: The goal was to study nutrient partitioning, ie, the proportion of weight change attributable to changes in fat mass (FM) versus protein mass (PM), during anti mycobacterial treatment. Design: Body-composition measures were made of 21 men and 9 women with pulmonary tuberculosis at baseline and after 1 and 6 mo of treatment. All subjects underwent dual-energy X-ray absorptiometry and deuterium bromide dilution tests, and a four-compartment model of FM, total body water (TBW), bone minerals (BM), and PM was derived. The ratio of PM to FM at any time was expressed as the energy content (p-ratio). Changes in the p-ratio were related to disease severity as measured by radiologic criteria. Results: Patients gained 10% in body weight (P < 0.001) from baseline to month 6. This was mainly due to a 44% gain in FM (P < 0.001); PM, BM, and TBW did not change significantly. Results were similar in men and women. The p-ratio decreased from baseline to month 1 and then fell further by month 6. Radiologic disease severity was not correlated with changes in the p-ratio. Conclusions: Microbiological cure of tuberculosis does not restore PM within 6 mo, despite a strong anabolic response. Change in the p-ratio is a suitable parameter for use in studying the effect of disease on body composition because it allows transformation of such effects into a normal distribution across a wide range of baseline proportion between fat and protein mass.

Stereoselective synthesis of vinyl germanes and silanes. Applications of tris(trimethyl)germanes and silanes in Pd-catalyzed cross -coupling reactions

Although group 14 organometallic compounds (Si, Sn) have been well developed as transmetallation reagents in cross-coupling reactions, the application of organogermanium compounds as cross-coupling reagents is still a relatively new area with few papers published. This study aimed to develop methods for the synthesis of new classes of vinyl germane and vinyl silane compounds, mainly Z and E tris(trimethylsilyl)germanes and silanes, which were then applied to Pd-catalyzed cross-couplings with aryl and alkenyl halides. The stereoselective radical-mediated desulfonylation of vinyl sulfones with tris(trimethyl)germanium or silane hydrides provided access to the synthesis of trans vinyl germanes or silanes. Alternatively hydrogermylation or hydrosilylation of terminal alkynes gave cis vinyl germanes or silanes. The application of these new classes of organometallic compounds in cross-coupling reactions with various aryl and alkenyl halides under aqueous [NaOH/H2O2/Pd(PPh 3)4] and anhydrous [KH/t-BuOOH/Pd(PPh 3)4] oxidative conditions were investigated. ^ It was found that the vinyl tris(trimethylsilyl)germanes successfully underwent Pd-catalyzed cross-couplings with aryl and alkenyl halides and aryl triflates under aqueous and anhydrous oxidative conditions. These procedures provided examples of "ligand-free" Pd-catalyzed coupling of organogermanes with aryl and alkenyl halides. Interestingly, couplings with fluorinated vinyl germanes appeared to occur more easily than with the corresponding (α-fluoro)vinyl stannanes and silanes since neither addition of an extra ligand nor activation with fluoride was necessary. The vinyl tris(trimethyl)silanes were found to be alternative substrates for the Hiyama reaction. The coupling of TTMS-silanes with various aryl, heteroaryl as well as alkenyl halides proceeded smoothly upon treatment with hydrogen peroxide in the presence of sodium hydroxide and fluoride ion. ^