Progress in the palladium-catalyzed cyanation of aryl chlorides

The development of new palladium catalysts for the cyanation of various aryl and heteroaryl chlorides is described. The combination of amine co-catalysts with chelating phosphine ligands, for example, 1,4-bis(diphenylphosphino)butane (dppb) or 1,5-bis(diphenylphosphino)pentane (dpppe), allows an efficient cyanation of chloroarenes with simple potassium cyanide. General palladium-catalyzed cyanation of nonactivated and deactivated chloroarenes is possible for the first time. Studies of the oxidative addition of aryl halides to palladium triphenylphosphine complexes in the presence and absence of amines suggest that the co-catalyst is capable of preventing catalyst deactivation caused by the presence of excess cyanide ions in solution.     

Mild and general methods for the palladium-catalyzed cyanation of aryl and heteroaryl chlorides

[reaction: see text] New methods for the palladium-catalyzed cyanation of aryl and heteroaryl chlorides have been developed, featuring sterically demanding, electron-rich phosphines. Highly challenging electron-rich aryl chlorides, in addition to electron-neutral and electron-deficient substrates, as well as nitrogen- and sulfur-containing heteroaryl chlorides can all undergo efficient cyanation under relatively mild conditions using readily available materials. In terms of substrate scope and temperature, these methods compare very favorably with the state-of-the-art cyanations of aryl chlorides.     

Ligand-free palladium-catalyzed cyanation of aryl halides

[reaction: see text] A practical, ligand-free cyanation of aryl bromides that utilizes as little as 0.1 mol % Pd(OAc)(2) in combination with a nontoxic cyanide source, M(4)[Fe(CN)(6)] (M = K, Na), is described. The reactions are performed in DMAC at 120 degrees C and provide the corresponding aryl nitrile in 83-96% yield, typically in less than 5 h. TON values of up to 7100 were attained.     

A mild and efficient palladium-catalyzed cyanation of aryl chlorides with K4[Fe(CN)6

An efficient palladium-catalyzed cyanation of aryl chlorides is established. In the presence of a highly effective Pd/CM-phos catalyst, cyanation of aryl chlorides proceeds at 70 °C in general, which is the mildest reaction temperature achieved so far for this process. Common functional groups such as keto, aldehyde, ester, nitrile and -NH(2), and heterocyclic coupling partners including N-H indoles are well tolerated. Moreover, a sterically hindered nonactivated ortho,ortho-disubstituted electrophile is shown to be a feasible coupling partner in cyanation.     

A facile, microwave-assisted, palladium-catalyzed arylation of acetone

We report an expedient method for the heteroarylation of acetone under tin-free conditions. The coupling is performed using the commercially available enol silane of acetone (2-trimethylsilyloxypropene) and a corresponding aryl bromide, chloride or triflate under microwave-assisted conditions, with tris(dibenzylideneacetone)dipalladium (Pd₂(dba)₃) or palladium acetate (Pd(OAc)₂) and 2-(2′,6′-dimethoxybiphenyl)dicyclohexylphosphine (S-Phos) as the catalyst system.     

The palladium-catalyzed desulfitative cyanation of arenesulfonyl chlorides and sodium sulfinates

A palladium-catalyzed desulfitative cyanation of arenesulfonyl chlorides and sodium sulfinates has been developed, providing aryl nitriles in moderate to excellent yields. It represents a facile procedure to access aryl nitriles.     

Efficient palladium-catalyzed N-arylation of a sulfoximine with aryl chlorides

The efficient N-arylation of a sulfoximine with aryl chlorides was developed by using Pd(2)(dba)(3) as a catalyst and various ligands. The reactions using RuPhos as a ligand afforded the coupled products in fair to excellent yields.     

An efficient palladium-catalyzed Heck coupling of aryl chlorides with alkenes

Catalyst system PdCl₂(PCy₃)₂/Cs₂CO₃ in dioxane was found to be the efficient catalyst system for Heck cross-coupling reactions of deactivated, neutral, and activated aryl chlorides with a variety of alkenes under mild conditions to afford selectively E-arylated alkenes in good to excellent yields.     

Triazole-based monophosphine ligands for palladium-catalyzed cross-coupling reactions of aryl chlorides

A variety of triazole-based monophosphines (ClickPhos) have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes. Their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides. Ligand 7i, which has a 2,6-dimethoxybenzene moiety, provided good results in Suzuki-Miyaura reaction to form hindered biaryls. A CAChe model for the Pd/7i complex shows that the likelihood of a Pd-arene interaction might be a rationale for its high catalytic reactivity.     

Ligand-supported palladium-catalyzed cross-coupling reactions of (hetero) aryl chlorides

The introduction of electron rich and sterically hindered ligands has made otherwise inert aryl chlorides and hetero aryl chlorides viable coupling partners in palladium-catalyzed Suzuki-Miyaura, Sonogashira, Stille and other types of cross-coupling reactions. This review gives highlights of cross-coupling of aryl chlorides employing in situ generated palladium catalytic systems.     

Statistical experimental design-driven discovery of room-temperature conditions for palladium-catalyzed cyanation of aryl bromides

A combination of Pd₂(dba)₃·CHCl₃ (0.5 mol %) and commercially available, air-stable phosphonium salt [(t-Bu)₃PH]BF₄ (1.4 mol %) in a presence of Zn powder and Zn(CN)₂ as the cyanide source comprises an extremely efficient catalyst system for the cyanation of a diverse array of aryl bromides, at room temperature. This result emerged from an experimental strategy that combines the advantages of parallel, automated experimentation with the design of experiments (DOE) for the effective definition of an optimal set of reaction conditions.     

Recent developments and perspectives in palladium-catalyzed cyanation of aryl halides: synthesis of benzonitriles

The palladium-catalyzed cyanation of Ar-X (X = I, Br, Cl, OTf, and H) allows for an efficient access towards benzonitriles. After its discovery in 1973 and following significant improvements in recent decades, this methodology has become nowadays the most popular for preparation of substituted aromatic nitriles. In this critical review, we summarize the important developments in this area from 2000 until 2010 (151 references).     

New ligands for a general palladium-catalyzed amination of aryl and heteroaryl chlorides

The synthesis and application of monodentate N-substituted heteroarylphosphines is described. In general, the ligands are conveniently prepared by selective metallation at the 2-position of the respective N-substituted heterocycle (pyrrole, indole) by using n-butyllithium/tetramethylethylenediamine (TMEDA) followed by quenching with dialkyl- or diarylchlorophosphines. Of the different ligands prepared, the new dialkyl-2-(N-arylindolyl)phosphines (cataCXium P) perform excellently in the palladium-catalyzed amination of aryl and heteroaryl chlorides. Coupling of both activated and deactivated chloroarenes proceeds under mild conditions (room temperature to 60 degrees C). By using optimized conditions remarkable catalyst productivity (total turnover number, TON, up to 8000) and activity (turnover frequency, TOF=14000 h(-1) at 75% conversion) are observed.     

Neopentylphosphines as effective ligands in palladium-catalyzed cross-couplings of aryl bromides and chlorides

The use of neopentylphosphine ligands in the palladium-catalyzed Suzuki, Sonogashira, Heck, and Hartwig-Buchwald couplings of aryl bromides and chlorides are reported. Di-tert-butylneopentylphosphine (DTBNpP) provided highly active catalysts for the coupling of aryl bromides at mild temperatures. Trineopentylphosphine, an air-stable trialkylphosphine, gave inactive catalysts at room temperature, but showed good activity in the H-B amination of aryl chlorides at elevated temperatures.     

A functionalized phosphine ligand with a pentaarylbenzene moiety in palladium-catalyzed Suzuki-Miyaura coupling of aryl chlorides

A functionalized phosphine with a pentaarylbenzene moiety was found to facilitate the palladium-catalyzed Suzuki-Miyaura coupling of aryl chlorides. The new ligand achieved high turnover numbers (up to TON 5000).     

Aqueous hydroxide as a base for palladium-catalyzed amination of aryl chlorides and bromides

The amination of aryl halides in the presence of inexpensive and air-stable alkali metal hydroxide bases and Pd[P(t-Bu)3]2 as catalyst gave arylamines in high yields. The reactions were conducted with a catalytic amount of cetyltrimethylammonium bromide as phase-transfer agent and either aqueous hydroxide or solid hydroxide in the presence of water. This combination of alkali metal hydroxide base, H2O, and the ammonium salt performed as well as NaO-t-Bu in the amination of p-chlorotoluene with dibutylamine. Hydroxide base was suitable for reactions of a wide range of aryl chlorides and bromides with aliphatic and aromatic amines. Some functional groups that were intolerant of tert-butoxide base, such as esters, enolizable ketones, nitriles, and nitro groups, were tolerated by the combination of hydroxide base, H2O, and cetyltrimethylammonium bromide in toluene solvent.     

Rapid palladium-catalyzed aminations of aryl chlorides with aliphatic amines under temperature-controlled microwave heating

Rapid Buchwald-Hartwig amination of electron neutral and rich aryl chlorides and bromides have been achieved using temperature-controlled microwave heating. Primary and secondary aliphatic amines can be coupled with these substrates in good yields within a reaction time of only 10 min.     

Sulfate additives generate robust and highly active palladium catalysts for the cyanation of aryl chlorides

The use of sulfate additives such as H₂SO₄ greatly increases the reactivity of palladium catalysts for the cyanation of aryl and heteroaryl chlorides and renders them more robust toward adventitious air. Using this method, a wide variety of aromatic and heteroaromatic nitriles were prepared in high yield.