Ligand-free copper-catalyzed O-arylation of arenesulfonamides with phenols: An unusual approach to biaryl ether synthesis

An unprecedented ligand-free copper-catalyzed O-arylation of arenesulfonamides with phenols has been developed. Thus, a range of unsysmmetric biaryl ethers were synthesized in excellent yields. The reaction occurs efficiently with excellent regioselectivity through the cleavage of C_ary–S bond and with a good tolerance of functional groups on the phenyl ring of phenols. The reaction is appreciated for its readily accessible substrates, mild conditions, and simple operation under air.     

Glyoxal bis(phenylhydrazone) as promoter for CuI-catalyzed O-arylation of phenols with bromoarenes

A very simple bishydrazone-type ligand, glyoxal bis(phenylhydrazone) (L1), was found to effectively promote the CuI-catalyzed O-arylation of phenols with aryl bromides. This cross-coupling reaction proceeded in acetonitrile at 60-80 °C in the presence of K₃PO₄ as base. A diverse array of phenols and bromoarenes was employed as substrates to afford diaryl ethers in good to excellent yields, and some base-sensitive groups, such as ester, aldehyde, and ketone groups, can survive under the mild reaction conditions.     

Efficient synthesis of substituted biaryl anilines and biaryl phenols via a Suzuki cross-coupling reaction

An efficient synthesis of biaryl building blocks with multiple point diversities via a Suzuki cross-coupling reaction using a commercially available preformed Pd catalyst 1 was reported. Substituted biaryl anilines and phenols were obtained in one step from commercially available aryl halides.     

Facile O-arylation of phenols and carboxylic acids

[reaction: see text] A facile, transition-metal-free O-arylation procedure for phenols and aromatic carboxylic acids has been developed that affords good to excellent yields of arylated products under very mild reaction conditions. A methoxy-substituted aryl triflate affords O-arylated products in high yields with excellent regioselectivity. This chemistry tolerates a variety of functional groups.     

Ligand-free copper-catalyzed O-arylation of nitroarenes with phenols

The first example of ligand-free copper-catalyzed O-arylation of nitroarenes with phenols was developed, achieving unsymmetrical diaryl ethers in moderate to excellent yields. This arylation proceeded smoothly without promotion of the ligands, and displayed great functional group compatibility. Thus, the method represents a new, facile, and cost-effective approach to access unsymmetrical diaryl ethers.     

Direct transformation of silyl enol ethers into functionalized allenes

The first elimination reactions of silyl enol ethers to lithiated allenes are reported. These reactions allow a direct transformation of readily available silyl enol ethers into functionalized allenes. The action of three to four equivalents of lithium diisopropylamide (LDA) on silyl enol ethers results in the formation of lithiated allenes by initial allylic lithiation, subsequent elimination of a lithium silanolate, and finally, lithiation of the allene thus formed. Starting with amide-derived silyl imino ethers, lithiated ketenimines are obtained. A variety of reactions of the lithiated allenes with electrophiles (chlorosilanes, trimethylchlorostannane, dimethyl sulfate and ethanol) were carried out. Elimination of silanolate is observed only for substrates that contain the hindered SiMe2tBu or Si(iPr)3 moiety, but not for the SiMe3 group. The reaction of 1,1-dilithio-3,3-diphenylallene with ketones provides a convenient access to novel 1,1-di(hydroxymethyl)allenes which undergo a domino Nazarov-Friedel-Crafts reaction upon treatment with p-toluenesulfonic acid.     

Stereoselective synthesis of functionalized vinyl ethers from allyl bromides activated by triethylamine

An efficient coupling reaction of allyl bromides with various alcohols as nucleophiles activated by triethylamine, leading to functionalized vinyl ethers in good yields and with full stereoselectivity.     

Intramolecular O-arylation of phenols with phenylboronic acids: application to the synthesis of macrocyclic metalloproteinase inhibitors

[reaction: see text]. The copper acetate mediated intramolecular O-arylation of phenols with phenylboronic acid pseudopeptides is the key step in the preparation of macrocyclic biphenyl ether hydroxamic acid inhibitors of collagenase 1 and gelatinases A and B. The intramolecular macrocyclization was found to be mild and tolerant of common chemical functionality. This methodology should provide a general route to macrocyclic biphenyl ethers.     

Direct synthesis of 3-fluoroalkyl-2,6-diethoxycarbonyl phenols

Cyclocondensation of α-fluoroalkyl ketones or α-fluoroalkyl aldehyde (1) and diethyl 1,3-acetonedicarboxylate (2) affords 3-fluoroalkyl-2,6-diethoxycarbonyl-5-alkyl-phenols (3) in good yields. This provides a novel method for the preparation of meta-fluoroalkyl polysubstituted phenols.     

Chemoselectivity in the Cu-catalyzed O-arylation of phenols and aliphatic alcohols

An orthogonal set of Cu-catalysts for the selective mono-arylation of alkyl aryl diols using aryl iodides is presented. Picolinic acid ligated copper catalyst provided phenol O-arylation only, while alkyl aryl ethers are generated by ligand-free copper catalyst in the presence of 2 equivalents NaOt-Bu.     

Cu-nanoparticle catalyzed O-arylation of phenols with aryl halides via Ullmann coupling

Recyclable Cu-nanoparticles provide an efficient, economic, and novel method for the synthesis of diaryl ethers via Ullmann type coupling. This method provides a wide range of substrate applicability and avoids the use of a heavy metal co-catalyst and gives diaryl ethers in satisfactory yields.     

A biaryl cross-coupling strategy for functionalisation of benzocrown ethers

Preparation of (di)benzocrown-substituted aryl-zinc or -boron reagents and their palladium-catalysed cross-coupling with functionalised aryl halides is described for convenient synthesis of novel crown ether systems.     

Direct synthesis of phenols by iron-catalyzed biphasic oxidation of aromatic hydrocarbons with hydrogen peroxide

The hydroxylation of a series of aromatic hydrocarbons with hydrogen peroxide, catalyzed by iron complexes with pyrazine-3-carboxylic acid N-oxide, was investigated, operating in a biphasic reaction medium.

The new catalyst showed a high selectivity to the corresponding phenols, minimizing the over-oxidation reactions to polyoxygenated derivatives and tars which, along with dimers formation, are the major limitations of the classical Fenton’s reagent for a practical synthetic application.

In the case of alkylbenzenes, the competitive side chain oxidation at the benzylic positions also occurred. Electron rich substrates, such as anisole, were oxidized with very poor selectivity.

The reactions were carried out in a biphasic system that allows a convenient recovery and recycling of the catalyst by phase separation techniques. The catalyst showed a complete retention of activity after six consecutive reaction cycles.

The new catalyst appears as a promising tool for the direct synthesis of phenols, in alternative to the conventional multi-step methods.     

Water as an efficient medium for the synthesis of functionalized enol ethers

Herein we report an efficient method for synthesis of β-alkylated and β,β-dialkylated α-iodo enol ethers in water. Radical addition in aqueous medium of ethyl iodoacetate, iodoacetonitrile, and iodoacetamide to ynol ethers leads to α-iodo enol ethers with moderate to excellent yields and high stereoselectivities.     

Palladium-catalysed synthesis of biaryl phosphines

Monodentate, biphenyl-type phosphines have emerged as a powerful class of ligands in homogeneous catalysis. Synthetic methods for these ligands are limited, however. We report that the palladium-catalysed Suzuki coupling of OPR₂(o-C₆H₄X) (R=Ph, t-Bu; X=Br, I) with arylboronic acids affords a variety of biaryl phosphine oxides including those that contain heterocycles. The corresponding phosphines are readily obtained by treatment with HSiCl₃. The methodology provides an easy entry to monodentate biaryl and heterobiaryl P^?X (X=N, O, S) phosphines with diverse steric and electronic properties.     

Efficient synthesis of biaryl lactones by domino retro-Michael-aldol-lactonization reactions

Biaryl lactones were prepared by novel domino retro-Michael-aldol-lactonization reactions of 2,3-dihydropyrans.     

Aerosol direct fluorination: Direct synthesis of perfluorinated glyme ethers

Aerosol direct fluorination of 1,2-dimethoxyethane, bis(2-methoxyethyl)ether, triethyleneglycol dimethyl ether, and tetraethyleneglycol dimethyl ether produced the perfluorinated analogs in 36%, 22%, 30% and 15% isolated yields based on total input of hydrocarbon into the reactor. High effluent concentrations in excess of 80% were obtained in all cases indicating that low yields are primarily due to mechanical losses, not fragmentation or incomplete reaction. The clean reaction and the ability to produce high molecular weight fluorocarbons by direct fluorination suggests the applicability of aerosol fluorination to the production of fluorinated fluids and oils.     

Synthesis of functionalized biaryl compounds via ring expansion of alkenylcyclobutenones

Various functionalized biaryls are accessible via a simple two-step process. Treatment of alkenylcyclobutenones with aryllithium provides ring-opened trienes, which are smoothly cycloaromatized under thermal conditions.