Reductive Hydroformylation of Isosorbide Diallyl Ether.

Isosorbide and its functionalized derivatives have numerous applications as bio-sourced building blocks. In this context, the synthesis of diols from isosorbide diallyl ether by hydrohydroxymethylation reaction is of extreme interest. This hydrohydroxymethylation, which consists of carbon-carbon double bonds converting into primary alcohol functions, can be obtained by a hydroformylation reaction followed by a hydrogenation reaction. In this study, reductive hydroformylation was achieved using isosorbide diallyl ether as a substrate in a rhodium/amine catalytic system. The highest yield in bis-primary alcohols obtained was equal to 79%.

Nickel-Catalyzed α-Allylation of Aldehydes and Tandem Aldol Condensation/Allylation Reaction with Allylic Alcohols.

An additive-free nickel-catalyzed α-allylation of aldehydes with allyl alcohol is reported. The reaction is promoted by 1 mol % of in situ formed nickel complex in methanol, and water is the sole by-product of the reaction. The experimental conditions allow the conversion of various α-branched aldehydes and α,ß-unsaturated aldehydes as nucleophiles. The same catalyst and reaction conditions enabled a tandem aldol condensation of aldehyde/α-allylation reaction.

Nickel-catalysed hydroalkoxylation reaction of 1,3-butadiene: ligand controlled selectivity for the efficient and atom-economical synthesis of alkylbutenyl ethers.

The nickel-catalysed hydroalkoxylation of butadiene is promoted by a nickel(0)/dppb catalyst (dppb = 1,4-bis(diphenylphosphino)butane; see scheme). By following this new synthetic procedure, alkylbutenyl ethers are readily obtained from an alcohol and 1,3-butadiene with exclusion of dimerisation and telomerisation products.

Synthesis of α-alkylated ß-ketoesters by alkoxycarbonylation/Michael addition domino reaction.

The palladium-catalyzed alkoxycarbonylation of an α-chloro ketone can be efficiently combined to a Michael addition reaction in a new two-step domino reaction, allowing the synthesis of original highly functionalized α-alkylated ß-ketoesters. The scope of the reaction was extended to several α-chloro ketones and Michael acceptors with moderate to very good yields.

Plausible PEPPSI catalysts for direct C-H functionalization of five-membered heterocyclic bioactive motifs: synthesis, spectral, X-ray crystallographic characterizations and catalytic activity.

In this study, a series of benzimidazolium salts were synthesized as asymmetric N-heterocyclic carbene (NHC) precursors. Nine novel palladium complexes with the general formula [PdX2(NHC)(pyridine)] were synthesized using benzimidazolium salts in the PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) theme. All synthesized Pd(ii) complexes are stable. The synthesized compounds were thoroughly characterized by respective spectroscopic techniques, such as 1HNMR, 13C NMR, FTIR spectroscopy, X-ray crystallography and elemental analysis. The geometric structure of the palladium N-heterocyclic carbene has been optimized in the framework of density functional theory (DFT) using the B3LYP-D3 dispersion functional with LANL2DZ as a basis set. The on/off mechanism of pyridine assisted Pd-NHC complexes made them the best C-H functionalized catalysts for regioselective C-5 arylated products. Five membered heterocyclic compounds such as 2-acetyl furan, furfuryl acetate 2-acetylthiophene and N-methylpyrrole-2-carboxaldehyde were treated with numerous aryl bromides and arylchlorides under optimal catalytic reaction conditions. Interestingly, all the prepared catalysts possessed essential structural features that facilitated the formation of desired coupling products in quantitative yield with excellent selectivity. The arylation reaction of bromoacetophenone was highly catalytically active with only 1 mol% catalyst loading at 150 °C for 2 hours. To check the efficiency of the synthesized complexes, three different five member heterocyclic substrates (2-acetylfuran, 2-acetylthiophen, 2-propylthaizole) were tested with a number of aryl bromides bearing both electron-donating and electron-withdrawing groups on para position. The data in Tables 2-4. Indicated that electron-donating groups on the para position of aryl halide decreased the catalytic conversion while electron-withdrawing groups increased the catalytic conversion this was due to the high nucleophilicity of the electron-donating substituents.

Copper-Catalyzed Asymmetric Hydroboration Reaction of Novel Methylene Isoindolinone Compounds through Microwave Irradiation and Their Antileishmanial and Antitoxoplasma Activities.

The aim of this study was devoted into molecular docking calculations to discover the potential antileishmania and antitoxoplasma activities of newly synthesized compounds obtained by applying a practical and simple method under microwave irradiation. All these compounds were tested in vitro for their biological activity against Leishmania major promastigotes, amastigotes, and Toxoplasma gondii tachyzoites. Compounds 2a, 5a, and 5e were the most active against both L. major promastigotes and amastigotes, with IC50 values of less than 0.4 µM mL-1. Compounds 2c, 2e, 2h, and 5d had a strong antitoxoplasma activity of less than 2.1 µM mL-1 against T. gondii. We can conclude that aromatic methyleneisoindolinones are potently active against both L. major and T. gondii. Further studies for mode of action evaluation are recommended. Compounds 5c and 5b are the best drug candidates for antileishmania and antitoxoplasma due to their SI values being over 13. The docking studies of compounds 2a-h and 5a-e against pteridine reductase 1 and T. gondii enoyl acyl carrier protein reductase reveal that compound 5e may be an effective antileishmanial and antitoxoplasma drug discovery initiative.

Effect of chain unsaturation on the self-association of tri- and tetraethylene glycol octyl ethers obtained by butadiene telomerization.

2,7-Octadienyl ethers of tri- and tetraethylene glycol (C(8:2)E(3) and C(8:2)E(4)) have been synthesized by the atom-economical butadiene telomerization of the corresponding poly(ethylene glycols). On one hand, this synthetic path is attractive because it is expeditious and environmentally benign, and on the other hand, it provides unconventional amphiphiles for which the lipophilic chains possess two double bonds. These two unsaturations increase the global hydrophilicity of the compound, which is also highlighted by the modelization of the compounds using the conductor-like screening model for real solvents (COSMO-RS). The behavior of C(8:2)E(3) and C(8:2)E(4) in binary amphiphile/water and ternary amphiphile/oil/water systems is therefore greatly modified compared to that of the conventional fully saturated homologues (C(8)E(3) and C(8)E(4)) that are easily obtained after hydrogenation. This results in a lowered efficiency of the unsaturated compounds for oil solubilization. The usual Winsor-type microemulsion systems are formed, and for the same oil, the DLS investigation of the microstructure of the Winsor I microemulsion does not highlight any difference in the self-association between the unsaturated and saturated compounds.

Synthesis and crystal structure of a new chiral α-amino-oxime nickel(II) complex.

A dinuclear nickel complex with (S)-limonene based amino-oxime ligand has been isolated and its crystal structure determined. The resolved structure of dichloridobis-{(2S,5R)-2-methyl-5-(prop-1-en-2-yl)-2-[(pyridin-2-yl)methyl-amino]-cyclo-hexan-1-one oxime}dinickel(II), [Ni2Cl2(C16H23ClN3O)2], at 100 K has monoclinic (P21) symmetry. The two NiII ions in the dinuclear complex are each coordinated in a distorted octa-hedral environment by three nitro-gen atoms, a terminal chloride and two µ bridging chlorides. Each oxime ligand is coordinated to nickel(II) by the three nitro-gen atoms, leading to two five-membered chelate rings, each displaying an envelope conformation. In the crystal, numerous inter-molecular and intra-molecular hydrogen bonds lead to the formation of a three-dimensional network structure.

Visible-Light-Driven CarboxyLic Amine Protocol (CLAP) for the Synthesis of 2-Substituted Piperazines under Batch and Flow Conditions.

Piperazines are privileged scaffolds in medicinal chemistry. Disclosed herein is a visible-light-promoted decarboxylative annulation protocol between a glycine-based diamine and various aldehydes to access 2-aryl, 2-heteroaryl, as well as 2-alkyl piperazines. The iridium-based complex [Ir(ppy)2(dtbpy)]PF6 and carbazolyl dicyanobenzene 4CzIPN were found to be the photocatalysts of choice to efficiently perform the transformation under mild conditions, whether in batch or in continuous mode.

The Palladium-Catalyzed Carboxytelomerization of Butadiene with Agrobased Alcohols and Polyols.

The palladium catalyzed carboxytelomerization reaction of alcohols with butadiene allows for efficient and atom-economical access to unsaturated alkyl nona-3,8-dienoate esters. The study focused on the nature of the catalyst (phosphine and acid) with ethanol. Commercially available triarylphosphines and carboxylic acids associated with a simple palladium precursor appear to be the best combination for in situ generation of the catalyst. The reaction conditions were further optimized and the carboxytelomerization reaction was efficiently applied to the full transformation of several industrially relevant agro-based monoalcohols and polyols.

Correction: Efficient in situ N-heterocyclic carbene palladium(ii) generated from Pd(OAc)2 catalysts for carbonylative Suzuki coupling reactions of arylboronic acids with 2-bromopyridine under inert conditions leading to unsymmetrical arylpyridine ketones: synthesis, characterization and cytotoxic activities.

[This corrects the article DOI: 10.1039/C8RA08897G.].

The Palladium-Catalyzed Carbonylative Telomerization Reaction with Phenols, Polyphenols and Kraft Lignin.

An efficient carbonylative coupling reaction of two equivalents of 1,3-butadiene, yielding aryl nona-3,8-dienoate esters, is performed with phenols as nucleophile, and promoted by palladium-based catalysts. Optimization study reveals the key role of benzoic acid as a cocatalyst. The suggested catalyst combination enables the conversion of a wide scope of variously substituted phenols into corresponding esters with a high yield. Further tests were performed with diphenols, naturally-occurring phenols and an industrial grade Kraft lignin, thus, indicating the scope of this reaction for transforming industrially relevant polyphenolic structures.

Palladium-Catalyzed Functionalization of Kraft Lignin: Ether Linkages through the Telomerization Reaction.

Kraft lignin was efficiently functionalized with octadienyl ether linkages through the palladium-catalyzed telomerization of 1,3-butadiene. Comparison with molecular model substrates assessed the grafting of phenols and alcohols and an optimization study led to up to 69 % conversion of the total number of hydroxyl groups present in lignin. This catalytic study evidenced the partial oxidation of triphenylphosphine into triphenylphosphine oxide and triphenylphosphine sulfide by contaminants present in the industrial grade kraft lignin. The telomerised lignin is a malleable material and a preliminary study of the thermal properties showed a decrease in the glass transition in comparison with the starting material.

Efficient in situ N-heterocyclic carbene palladium(ii) generated from Pd(OAc)2 catalysts for carbonylative Suzuki coupling reactions of arylboronic acids with 2-bromopyridine under inert conditions leading to unsymmetrical arylpyridine ketones: synthesis, characterization and cytotoxic activities.

N,N-Substituted benzimidazole salts were successfully synthesized and characterized by 1H-NMR, 13C {1H} NMR and IR techniques, which support the proposed structures. Catalysts generated in situ were efficiently used for the carbonylative cross-coupling reaction of 2 bromopyridine with various boronic acids. The reaction was carried out in THF at 110 °C in the presence of K2CO3 under inert conditions and yields unsymmetrical arylpyridine ketones. All N,N-substituted benzimidazole salts 2a-i and 4a-i studied in this work were screened for their cytotoxic activities against human cancer cell lines such us MDA-MB-231, MCF-7 and T47D. The N,N-substituted benzimidazoles 2e and 2f exhibited the most cytotoxic effect with promising cytotoxic activity with IC50 values of 4.45 µg mL-1 against MDA-MB-231 and 4.85 µg mL-1 against MCF7 respectively.

Biphasic Palladium-Catalyzed Hydroesterification in a Polyol Phase: Selective Synthesis of Derived Monoesters.

The palladium-catalyzed hydroesterification reaction was performed with polyols and olefins in a liquid/liquid biphasic system composed of unreacted polyol on the one hand and apolar reaction products/organic solvents on the other hand. The palladium-based catalyst was immobilized in the polyol phase thanks to the use of cationic triarylphosphines possessing pendent protonated amino groups in the acidic reaction medium or to the sulfonated phosphine TPPTS (trisodium triphenylphosphine-3,3',3''-trisulfonate). Owing to the insolubility of the products in the catalytic phase, this approach allowed the synthesis of monoesters of polyols with high selectivities as well as the easy separation of the catalyst through simple decantation.

New synthesis of 1,4-diketones via rhodium-catalysed 1,4 carbonylative addition of arylboronic acids to alpha,beta-unsaturated ketones.

The reaction of various arylboronic acids with alpha,beta-unsaturated ketones under CO pressure and in the presence of rhodium catalyst yields 1,4-diketones.

Synthesis of 1,4:3,6-dianhydrohexitols diesters from the palladium-catalyzed hydroesterification reaction.

The hydroesterification of alpha olefins has been used to synthesize diesters from bio-based secondary diols: isosorbide, isomannide, and isoidide. The reaction was promoted by 0.2% palladium catalyst generated in situ from palladium acetate/triphenylphosphine/para-toluene sulfonic acid. Optimized reaction conditions allowed the selective synthesis of the diesters with high yields and the reaction conditions could be scaled up to the synthesis of hundred grams of diesters from isosorbide and 1-octene with solvent-free conditions.

Pd-catalyzed domino carbonylative-decarboxylative allylation: an easy and selective monoallylation of ketones.

In the presence of an allyl alcohol, α-chloroacetophenones undergo an allyloxycarbonylation reaction followed by in situ decarboxylative allylation to selectively afford the corresponding monoallylated ketones via a Pd-catalyzed domino sequence. The scope of the reaction was extended to substituted α-chloroacetophenones as well as various allyl alcohols.

Telomerisation of 1,3-butadiene with 1,4:3,6-dianhydrohexitols: an atom-economic and selective synthesis of amphiphilic monoethers from agro-based diols.

The telomerisation of 1,3-butadiene with a Pd/TPPTS catalytic system in water or an organic solvent was used for the synthesis of C8 ethers from isosorbide, an agro-based diol. The use of water/oil biphasic reaction conditions allowed the selective synthesis of monoethers with improved rates upon using inorganic bases as promotors. As isosorbide is a non-symmetric diol, the two hydroxyl groups display different reactivities. 2-O-substituted-monoethers were preferentially obtained if water was used as the solvent, whereas in DMSO 5-O-substituted monoethers were the major products. Complete conversions of isosorbide with up to 94% monoether selectivities were obtained. The optimized reaction conditions were successfully applied to isomannide and isoidide for the selective synthesis of the derived ethers. An improved reactivity of the endo-hydroxy groups of isosorbide and isomannide versus the exo-hydroxy groups of isosorbide and isoidide was observed if the reaction was performed in DMSO instead of water.