Synthesis of symmetrical and unsymmetrical N,N'-diaryl guanidines via copper/N-methylglycine-catalyzed arylation of guanidine nitrate

CuI/N-methylglycine-catalyzed coupling reaction of guanidine nitrate with both aryl iodides and bromides takes place at 70-100 °C, affording symmetrical N,N'-diaryl guanidines with good to excellent yields. Unsymmetrical N,N'-diaryl guanidines can be assembled via monoarylation of guanidine nitrate with aryl iodides bearing a strong electron-withdrawing group and subsequent coupling with another aryl iodide.     

Aqueous sodium hydroxide promoted cross-coupling reactions of alkenyltrialkoxysilanes under ligand-free conditions

Fluoride-free cross-coupling reactions of alkenyltrialkoxysilanes with aryl iodides, bromides, and chlorides are performed on water using sodium hydroxide as activator at 120 degrees C under normal or microwave heating. This process occurs in the presence of Pd(OAc)(2) or 4-hydroxyacetophenone oxime-derived palladacycle 1 as precatalysts under ligand-free conditions with low Pd loadings (0.01-1 mol %) and using tetra-n-butylammonium bromide as additive. Different commercially available vinylalkoxylsilanes can be cross-coupled under these reaction conditions to the corresponding styrenes, the best substrates being vinyltrimethoxy- or vinyltriethoxysilane. Alkenyltriethoxysilanes, prepared by Wilkinson-catalyzed hydrosilylation of alkynes with triethoxysilane, are stereospecifically arylated with aryl and vinyl halides under microwave irradiation in moderate to high beta/alpha regioselectivity affording unsymmetrical stilbenes, alkenylbenzenes, and conjugate dienes, respectively. This simple procedure allows the palladium recycling from the aqueous phase during three runs by extractive separation of the products, which contain very low levels of Pd (21-27.5 ppm for an aryl iodide and up to 76 ppm for a bromide).     

Palladacycle-Catalyzed Carbonylation of Aryl Iodides or Bromides with Aryl Formates

An efficient palladacycle-catalyzed aromatic carbonylation reaction of aryl formates with aryl iodides or bromides has been developed. Commercially available and easily prepared aryl formates were employed as carbonyl sources without the use of external carbon monoxide. The present catalytic system shows broad functional group tolerance and affords aryl benzoate derivatives in good to excellent yields.     

Oxime‐derived palladacycle Immobilized in an Ionic Liquid Brush as an Efficient and Reusable Catalyst for Mozoroki‐Heck Reaction in Neat Water

An efficient and reusable heterogeneous catalyst with oxime‐derived palladacycle immobilized in an ionic liquid brush has been synthesized and an environmentally‐friendly procedure have been developed for coupling aryl iodides and bromides with acrylic acid. These reactions were conducted in neat water under aerobic conditions with water‐insoluble or even solid aryl halides and they proceeded smoothly and cleanly without any organic co‐solvent or other additives. The ionic liquid brush could be easily recovered and reused at least five times without significant loss of activity. The protocol has the advantages of excellent yields, environmental friendliness, and catalyst recyclability.     

Heck-type coupling vs. conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyl compounds: a systematic investigation

The competition between Heck-type coupling and conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyls has been systematically investigated in a toluene-H(2)O biphasic system. Aside from the intrinsic nature of rhodium and the enolization of carbonyls, the phosphine supporting ligand on rhodium, the ratio of aryl boronic acid to alpha,beta-unsaturated carbonyl and the pH value of the aqueous phase were found to affect the competition significantly. Highly selective rhodium-based catalyst systems have therefore been developed for both Heck-type coupling and conjugate addition by synergistically tuning the supporting ligand, the boronic acid to olefin ratio and other reaction conditions. Conjugate addition with selectivity >99% and Heck-type coupling with selectivity of up to 100%, 98% and 84% for acrylates, acrylamides and methyl vinyl ketone, respectively, could be achieved in the rhodium-catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyls using the corresponding optimized rhodium-based catalyst systems.     

Understanding sulfone behavior in palladium-catalyzed domino reactions with aryl iodides

Unlike traditionally used acyclic 1,2-disubstituted alkenes, the reaction of alpha,beta-unsaturated phenyl sulfones with aryl iodides under Heck reaction conditions takes place mainly by means of a four-component domino process, involving one unit of the alkene and three units of the aryl iodide, affording substituted 9-phenylsulfonyl-9,10-dihydrophenanthrenes. We report here the results of a computational study on the mechanism of this domino arylation reaction. Based on these results we can explain why vinyl sulfones, unlike other electron-deficient alkenes such as enones, preferentially follow this domino pathway instead of the usual Heck pathway. The key step is a C-H activation process in which a five-membered palladacycle is formed. The greater ability of vinyl sulfones, relative to enones, to reach the transition state that leads to the formation of the initial palladacycle makes the difference.     

Cross-coupling reactions of (1-fluorovinyl)methydiphenylsilane(1) with aryl halides and aryl triflates

The cesium fluoride (CsF)-assisted cross-coupling reaction of (1-fluorovinyl)methyldiphenylsilane (1) with aryl halides and aryl triflates was examined. The reaction with aryl iodides smoothly proceeded to afford the corresponding (1-fluorovinyl)arenes in the presence of a catalytic amount of CuI and Pd(PPh(3))(4) in aprotic polar solvents such as DMF, DMI, DMA, and NMP in good yields. A variety of functional groups (nitro, ester, ketone, and ether) on the aromatic rings can be tolerated under these mild conditions. Aryl iodides are superior to aryl bromides as the coupling reaction partner. The cross-coupling reaction of 1 with aryl triflates instead of aryl halides was also accomplished in the presence of tetrabutylammonium iodide (n-Bu(4)NI) as the additive under similar conditions.     

Controlled mono and double Heck reactions in water catalyzed by an oxime-derived palladacycle

The mono and β,β-diarylation of α,β-unsaturated carbonyl compounds with electron-deficient and electron-rich aromatic iodides in water is described. These reactions are catalyzed by the p-hydroxyacetophenone oxime-derived palladacycle 1 by controlling the stoichiometry of the aryl iodide and the alkene as well as the loading of the palladium catalyst. This one-pot protocol is performed in refluxing water and (dicyclohexyl)methylamine as base under thermal or microwave conditions and in the absence of an inert atmosphere.     

Low pressure vinylation of aryl and vinyl halides via Heck-Mizoroki reactions using ethylene

Aryl bromides and iodides in the presence of catalytic amounts of a palladacycle derived from acetophenone oxime and 2 equiv of potassium acetate react with ethylene under ambient pressure (15-30 psi) to give the corresponding vinylarenes. The reactions work with both electron-deficient and electron-rich aryl compounds and tolerate wide variety of common functional groups. Vinyl bromides lead to 1,3-dienes in moderate yields.     

Palladium-catalyzed cascade reaction of alpha,beta-unsaturated sulfones with aryl iodides

Unlike traditionally used acyclic 1,2-disubstituted alkenes, the reaction of alpha,beta-unsaturated phenyl sulfones with aryl iodides under Heck reaction conditions (Pd(OAc)(2) as catalyst, Ag(2)CO(3) as base in DMF at 120 (0)C) takes place mainly by a cascade process, involving one unit of the alkene and three units of the aryl iodide, to afford a substituted 9-phenylsulfonyl-9,10-dihydrophenanthrene. The dominant formation of this 3:1 coupling product, instead of the Heck trisubstituted olefin, shows that aromatic C-H bond activation processes can compete with the usually fast syn beta-hydrogen elimination step in the Heck arylation of an acyclic olefin. The structural scope of this palladium-catalyzed cascade arylation of alpha,beta-unsaturated sulfones has proved to be wide with regard to substitution at the beta-position (alkyl, aryl, or alkenyl substitution), substitution at the sulfone unit (alkyl or phenyl sulfones), and configuration at the CdoublebondC bond (trans or cis). Moreover, although less favored than in the case of the arylation of alpha,beta-unsaturated sulfones, similarly substituted 9,10-dihydrophenanthrenes have also been obtained in the case of alpha,beta-unsaturated phosphine oxides and alpha,beta-unsaturated phosphonate esters. A Pd(0)-Pd(II)-Pd(IV) mechanistic pathway involving the successive formation of highly electrophilic sigma-alkylpalladium intermediates and palladacycles is proposed for this multicomponent arylation.     

Diastereoselective conjugate addition to chiral alpha,beta-unsaturated carbonyl systems in aqueous media: an enantioselective entry to alpha- and gamma-hydroxy acids and alpha-amino acids

The stereoselectivity of the ultrasonically induced zinc--copper conjugate addition of iodides to chiral alpha,beta-unsaturated carbonyl systems under aqueous conditions was studied. Alkyl iodides add diastereoselectively to methylenedioxolanone 1 and methyleneoxazolidinone 2 to afford the 1,4-addition products in good yields (38-95 %) and with high diastereomeric excess (44-90 % de). The 1,4-addition to chiral gamma,delta-dioxolanyl-alpha,beta-unsaturated esters 3-5 also proceeds with good yields (51-99 %). The diastereoselectivity is dependent on the geometry of the olefin: the Z isomer 3 gives high diastereoselectivity, while the reactions with the E isomer 4 are nonstereoselective. The reaction proceeds with excellent chemoselectivity and allows the use of iodides bearing ester, hydroxy, and amino groups. Since the 1,4-addition products can be readily hydrolyzed, this methodology constitutes a novel entry for the enantioselective synthesis of alpha- and gamma-hydroxy acids and alpha-amino acids in aqueous media. The results obtained support the radical mechanism proposed by Luche, and represent one of the few examples of a radical stereoselective conjugate addition in aqueous medium.     

Pyrrole-2-carboxylic acid as a ligand for the Cu-catalyzed reactions of primary anilines with aryl halides

Pyrrole 2-carboxylic acid (L5) was found to be an effective ligand for the Cu-catalyzed monoarylation of anilines with aryl iodides and bromides. Under the reported conditions (10% CuI/20% L5/DMSO/K3PO 4/80-100 degrees C/20-24 h), a variety of useful functional groups were tolerated, and moderate to good yields of the diaryl amine products were obtained.     

Amino acid promoted CuI-catalyzed C-N bond formation between aryl halides and amines or N-containing heterocycles

CuI-catalyzed coupling reaction of electron-deficient aryl iodides with aliphatic primary amines occurs at 40 degrees C under the promotion of N-methylglycine. Using l-proline as the promoter, coupling reaction of aryl iodides or aryl bromides with aliphatic primary amines, aliphatic cyclic secondary amines, or electron-rich primary arylamines proceeds at 60-90 degrees C; an intramolecular coupling reaction between aryl chloride and primary amine moieties gives indoline at 70 degrees C; coupling reaction of aryl iodides with indole, pyrrole, carbazole, imidazole, or pyrazole can be carried out at 75-90 degrees C; and coupling reaction of electron-deficient aryl bromides with imidazole or pyrazole occurs at 60-90 degrees C to provide the corresponding N-aryl products in good to excellent yields. In addition, N,N-dimethylglycine promotes the coupling reaction of electron-rich aryl bromides with imidazole or pyrazole to afford the corresponding N-aryl imidazoles or pyrazoles at 110 degrees C. The possible action of amino acids in these coupling reactions is discussed.     

2,2′-Diamino-6,6′-dimethylbiphenyl as an efficient ligand in the palladium-catalyzed Suzuki–Miyaura and Mizoroki–Heck reactions

2,2′-Diamino-6,6′-dimethylbiphenyl was found to be an efficient ligand in the palladium-catalyzed Suzuki–Miyaura coupling reactions of aryl iodides, bromides, and chlorides and Mizoroki–Heck reactions of aryl iodides and bromides. Under appropriate conditions, all reactions gave the desired products in moderate to excellent yields. The ligand is inexpensive, air-stable and easy to available.     

Copper/oxalohydrazide/ketone catalyzed synthesis of primary arylamines via coupling of aryl halides with aqueous ammonia in water

The coupling reaction of aryl halides with aqueous ammonia was catalyzed by copper/oxalohydrazide/ketone system in water to yield primary arylamines without inert atmosphere. This method was fast and facile. The coupling reaction proceeded at 90 °C for 20-80 min, or at room temperature for a prolonged reaction time. A variety of aryl bromides and iodides were found to be applicable to this three-component catalytic system, which afforded good to excellent isolated yields.     

Sonogashira Coupling Reaction with Palladium Powder,Potassium Fluoride in Aqueous Media

Abstract

A Sonogashira coupling reaction of aromatic iodides and bromides with terminal alkynes in the presence of palladium powder, potassium fluoride, cuprous iodide, and triphenylphosphine in aqueous media was developed. The reaction generates the corresponding coupling products aryl alkynes in good to excellent yields.     

Mild ketone formation via Ni-catalyzed reductive coupling of unactivated alkyl halides with acid anhydrides

Ni-catalyzed ketone formation through mild reductive coupling of a diverse set of unactivated alkyl bromides and iodides with particularly aryl acid anhydrides was successfully developed using zinc as the terminal reductant. These conditions also allow direct coupling of alkyl iodides with aryl acids in the presence of Boc(2)O and MgCl(2).     

Copper-diamine-catalyzed N-arylation of pyrroles, pyrazoles, indazoles, imidazoles, and triazoles

This paper details the copper-catalyzed N-arylation of pi-excessive nitrogen heterocycles. The coupling of either aryl iodides or aryl bromides with common nitrogen heterocycles (pyrroles, pyrazoles, indazoles, imidazoles, and triazoles) was successfully performed in good yield with catalysts derived from diamine ligands and CuI. General conditions were found that tolerate functional groups such as aldehydes, ketones, alcohols, primary amines, and nitriles on the aryl halide or heterocycle. Hindered aryl halides or heterocycles were also found to be suitable substrates using the conditions reported herein.     

Active palladium catalyst supported by bulky diimine ligand catalyzed Suzuki–Miyaura coupling reaction in water under phosphane‐free and low catalyst loading conditions

A new catalytic system based on palladium and bulky diimine ligand for Suzuki–Miyaura coupling reaction of aryl iodides, bromides and chlorides in neat water is described. The desired biphenyl products were obtained in high to excellent yields for aryl iodides and bromides in the presence of low catalyst loading. Air‐stable catalyst has been recycled for the reaction of iodobenzene with phenylboronic acid for five consecutive runs. Copyright © 2014 John Wiley & Sons, Ltd.     

Efficient and highly regioselective direct C-2 arylation of azoles, including free (NH)-imidazole, -benzimidazole and -indole, with aryl halides

The Pd- and Cu-mediated reaction of a large variety of π-electron sufficient heteroarenes, which include free (NH)-imidazoles, -benzimidazole and -indole, with aryl iodides under ligandless and base-free conditions provides regioselectively the required 2-arylheterocycle derivatives in high yields. 2-Aryl-1-phenyl-1H-imidazoles can also be prepared by a one-pot domino HALEX and Pd- and Cu-mediated arylation reactions of 1-phenyl-1H-imidazole with activated and unactivated aryl bromides under base-free and ligandless conditions. The protocol for the synthesis of 2-arylazoles involving the use of aryl iodides has been found to be suitable for the efficient preparation of three bioactive compounds and a key intermediate in the synthesis of a heparanase inhibitor.