A one-pot synthesis of substituted salicylnitriles

Phenols were converted to salicylaldehydes with paraformaldehyde, MgCl₂-Et₃N in THF, and subsequent treatment with aqueous ammonia gave the corresponding imines which were oxidized with IBX to the desired salicylnitriles. The sequence of reactions was conveniently carried out as a one-pot procedure under mild conditions.     

One-pot synthesis of substituted catechols from the corresponding phenols

Phenols are converted to salicylaldehydes with paraformaldehyde, MgCl₂-Et₃N in THF, and when subsequently treated with aqueous NaOH and H₂O₂ afford the corresponding catechols. The sequence is conveniently carried out as a one-pot procedure.     

ortho-Formylation of estrogens. Synthesis of the anti-cancer agent 2-methoxyestradiol

Several estrogens were mono-formylated using a mixture of paraformaldehyde, MgCl₂, and Et₃N in refluxing THF. In all cases, the 2-isomer was formed as the major product with high regioselectivity compared to the 4-isomer. Excellent to high yields were obtained in all examples except one. The method was applied for an efficient synthesis of the anti-cancer agent 2-methoxyestradiol.     

Imidazolium salicylaldimine frameworks for the preparation of tridentate N-heterocyclic carbene ligands

Sterically hindered salicylaldimine functionalized imidazolium salts 2 have been prepared. The structures of the synthesized compounds were determined by spectroscopic techniques. The reaction of these salts containing arylmethyl-N chain (aryl: phenyl (2a), 2,4,6-trimethylphenyl (2b), 2,3,4,5,6-pentamethylphenyl (2c)) with Pd(OAc)₂ in boiling toluene afforded Pd(II) complexes 3 in high yields. The X-ray structure of 1-[3-(3,5-di-tert-butyl-2-oxophenyl)propyliminato]-3-(2,4,6-trimethylbenzyl)imidazol-2-ylidenebromopalladium(II) (3b) has been determined. The Suzuki-Miyaura reaction was used to investigate their activity as catalysts either prepared in situ or from well-defined complexes. They are efficient when activated arylbromides are used as substrates.     

A high yielding one-pot, novel synthesis of carbamate esters from alcohols using Mitsunobu's reagent

A novel process for the one-step conversion of primary alcohols into carbamates as protected amines has been developed using Mitsunobu's reagent in the presence of gaseous carbon dioxide. Thus, carbamate esters of the different amines were prepared in very good to excellent yields.     

Copper-catalyzed three-component one-pot synthesis of quinazolines

Two efficient approaches to multi-substituted quinazolines by the three-component one-pot reaction of o-bromo aromatic ketones/aldehydes, ammonia water and aromatic aldehydes, or primary alcohols catalyzed by CuCl have been developed.     

ortho-Formylation of oxygenated phenols

Oxygenated phenols are mono-formylated using a mixture of paraformaldehyde, MgCl₂, and Et₃N in THF. In all cases but one, only one regioisomer of the salicylaldehyde is obtained in good to high yield.     

One-pot synthesis of ortho-hydroxycinnamate esters

Phenols are converted to salicylaldehydes with paraformaldehyde, MgCl₂-Et₃N in THF, and subsequent treatment with methyl (triphenylphosphoranylidene)acetate gave the corresponding methyl ortho-hydroxycinnamate derivatives. The sequence is conveniently carried out as a one-pot procedure.     

A general method for the preparation of perfluoroalkanesulfonyl chlorides

A mild two-step synthesis of perfluoroalkanesulfonyl chlorides starting from perfluoroalkyl iodides has been developed. Reaction of perfluoroalkyl iodides with sodium dithionite gave sodium perfluoroalkanesulfinate salts which were converted into perfluoroalkanesulfonyl chlorides in 25-73% yield (two steps) using N-chlorosuccinimide.     

One-pot metal templated synthesis for the preparation of 2-quinoxalinol salen metal complexes

Metal complexes of 2-quinoxalinol salen (salqu) ligands can be prepared in a one-pot metal templated synthesis resulting in significantly enhanced yields than if the ligand were prepared and isolated prior to introducing the metal for complexation. Using this method, 12 salqu metal complexes have been prepared and characterized from +2 metal ions.     

A mild high yielding synthesis of oxazole-4-carboxylate derivatives

Several 2,5-disubstituted oxazole-4-carboxylates were prepared in high yields from the methyl esters of N-acyl-β-halodehydroaminobutyric acid derivatives by treatment with a 2% solution of DBU in acetonitrile. The scope of this reaction was investigated and it was found that dehydrodipeptides having a β-bromodehydroaminobutyric acid residue gave the corresponding oxazoles in good yields. The photophysical properties of some of the oxazoles prepared were studied in four solvents of different polarity. All compounds have reasonable high fluorescence quantum yields and a moderate solvent sensitivity, which makes them good candidates to be used as fluorescent probes. One of the fluorescent oxazoles prepared was inserted after cleavage of the methyl ester into two model peptides using a conventional solution phase strategy. The photophysical properties of the labelled peptides were studied in ethanol and water and compared with those of the oxazole. The results obtained showed that the oxazole maintains a good fluorescence level and the same solvent sensitivity when linked to a peptide chain.     

An efficient one-pot synthesis of annulated pyridines utilising a directed ortho-metallation/transmetallation approach

The ortho-alkylation of Boc-protected aminopyridines with α,ω-dihaloalkanes followed by in situ cyclisation, resulted in the corresponding annulated pyridine derivatives in good to excellent yields. The effect of the alkylating and chelating agents, the transmetallation additives and the directing group was examined.     

New pinene-derived pyridines as bidentate chiral ligands

A synthesis of new bidentate pyridines 8a-d, 9, and 10 has been developed, starting from triflate 14, readily available from β-pinene 11. A copper complex of the pyridine-oxazoline ligands 8a has been found to catalyze asymmetric allylic oxidation of cyclic olefins 36a-c with good conversion rates and acceptable enantioselectivity (≤67% ee). The imidazolium salt 10 has been identified as a precursor of the corresponding N,N′-unsymmetrical N-heterocyclic carbene ligand, whose complex with palladium catalyzed the intramolecular amide enolate α-arylation leading to oxindole 45 in excellent yield but with low enantioselectivity.     

A novel method for preparation of imidazolium tetrafluoroborate ionic liquids

A new method for the preparation of substituted imidazolium tetrafluoroborate salt, some of which are known as versatile room temperature ionic liquids, is proposed. The new method based on N-methylation of imidazole provided tetrafluoroborate derivatives containing no counterions, with shorter time and lower cost than conventional ion-exchange method.     

The one-pot halomethylation of 5-substituted salicylaldehydes as convenient precursors for the preparation of heteroditopic ligands for the binding of metal salts

The one-pot bromo- and chloro-methylation of various 5-substituted salicylaldehydes with paraformaldehyde and hydrobromic or hydrochloric acid has been achieved. This approach establishes a convenient and flexible method to attach functional arms to salicylaldehydes for further applications in organic and coordination chemistry. Examples are described using 3-bromomethyl-5-t-butylsalicylaldehyde in the synthesis of piperazine-containing heteroditopic ligands as receptors for metal salts.     

π-Acidity and π-basicity of N-heterocyclic carbene ligands. A computational assessment

In this contribution we report on a systematic analysis of the bond between transition metals and N-heterocyclic carbene (NHC) ligands. We compare the σ and π-contributions in a series of complexes in which the formal d-electron count ranges from d⁰ to d¹⁰. Our results confirm the currently accepted idea that NHC are not pure σ-donors. In the series of complexes examined here π-contribution is 10% at least. Moreover, remarkable metal-to-ligand backdonation occurs also for d⁰ complexes, and many systems present a substantial ligand-to-metal π donation.     

Influence of structural changes in ferrocene phosphane aminophosphane ligands on their catalytic activity

New phosphane aminophosphane ligands based on [3]ferrocenophane skeleton were synthesized using a direct double lithiation followed by phosphanylation. Influence of ligand structure on catalytic performance was evaluated by performing a series of Pd-catalyzed allylic substitution on different substrates. Enantioselectivities up to 55% ee were obtained with bridged ligand compared to 33% ee with analogous non-bridged BoPhoz ligand.     

An effective procedure for the preparation of 3-substituted-4- or 6-azaindoles from ortho-methyl nitro pyridines

3-Substituted-4- and 6-azaindoles were prepared from ortho-methyl-nitropyridines in a practically convenient, one-pot process based on the Leimgruber-Batcho reaction. The procedure comprises a sequence of (a) condensation of an ortho-methyl-nitropyridine with N,N-dimethylformamide dimethyl acetal; (b) alkylation or acylation of the enamine intermediate; (c) reduction of the nitro group to an aniline with in situ cyclization and elimination of dimethylamine to generate the 3-substituted azaindole heterocycle.     

A study on the metalation of alkoxydibromobenzenes

The metalation of (quasi)alkoxy-substituted dibromobenzenes C₆H₃(OR)Br₂ with lithium diisopropylamide (LDA) has been investigated. For 1-(quasi)alkoxy-3,5-dibromobenzenes (R = Me, TMS), different selectivities were observed depending on reaction conditions and the size of the alkoxy group. The methoxy group was an effective ortho-director whereas this was not the case for the bulky trimethylsilyloxy group. The metalation of related 2,5-dibromoanisole was also examined showing a significant meta-directing effect by the methoxy group. The thermal stability of aryllithium intermediates is significantly lower when lithium is flanked by a bromine and a methoxy group, whereas 4-(quasi)alkoxy-2,6-dibromoaryllithiums are less labile.