Efficient copper-free Sonogashira coupling of aryl chlorides with palladium on charcoal

Palladium on charcoal serves as an efficient and reusable solid supported catalyst for the Sonogashira coupling of aryl chlorides with terminal acetylenes in the presence of a bulky, electron-rich biphenyl type ligand (XPhos), without copper co-catalyst.     

An efficient system for the Pd-catalyzed cross-coupling of amides and aryl chlorides

A catalyst based on a new biarylphosphine ligand (3) for the Pd-catalyzed cross-coupling reactions of amides and aryl chlorides is described. This system shows the highest turnover frequencies reported to date for these reactions, especially for aryl chloride substrates bearing an ortho substituent. An array of amides and aryl chlorides were successfully reacted in good to excellent yields.     

Rapid and efficient microwave-assisted synthesis of aryl aminobenzophenones using Pd-catalyzed amination

Substituted aryl aminobenzophenone p38 MAP kinase inhibitors were synthesized in good to excellent yields using palladium-catalyzed aryl amination under conditions of microwave irradiation. Various ligands have been screened, and the reaction conditions were optimized. These coupling reactions are suitable for various anilines and aryl bromides that bear a variety of functional groups. Some leaving groups (iodides, chlorides, triflates, and tosylates) other than bromides have also been investigated. By this method, a large number of aryl aminobenzophenone p38 MAP kinase inhibitors were prepared in short order.     

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.     

Palladium-catalyzed coupling reactions of aryl chlorides

Collectively, palladium-catalyzed coupling reactions represent some of the most powerful and versatile tools available to synthetic organic chemists. Their widespread popularity stems in part from the fact that they are generally tolerant to a large number of functional groups, which allows them to be employed in a wide range of applications. However, for many years a major limitation of palladium-catalyzed coupling processes has been the poor reactivity of aryl chlorides, which from the standpoints of cost and availability are more attractive substrates than the corresponding bromides, iodides, and triflates. Traditional palladium/triarylphosphane catalysts are only effective for the coupling of certain activated aryl chlorides (for example, heteroaryl chlorides and substrates that bear electron-withdrawing groups), but not for aryl chlorides in general. Since 1998, major advances have been described by a number of research groups addressing this challenge; catalysts based on bulky, electron-rich phosphanes and carbenes have proved to be particularly mild and versatile. This review summarizes both the seminal early work and the exciting recent developments in the area of palladium-catalyzed couplings of aryl chlorides.     

Highly efficient and functional-group-tolerant catalysts for the palladium-catalyzed coupling of aryl chlorides with thiols

The cross-coupling reaction of aryl chlorides with aliphatic and aromatic thiols catalyzed by palladium complexes of the strongly binding bisphosphine CyPF-tBu ligand (1) is reported. Most of the reactions catalyzed by complexes of ligand 1 occur with turnover numbers that exceed those of previous catalysts by two orders of magnitude. The reactions occur with excellent yields, broad scope and high tolerance of functional groups. Coupling of aryl halides with thiols in the presence of low loadings of catalysts derived from other Josiphos type ligands, as well as ligands of other structural types, are also described.     

An efficient and general method for the Heck and Buchwald-Hartwig coupling reactions of aryl chlorides

The β-diketiminatophosphane Pd complex acted as a powerful catalyst for the Heck coupling of aryl chlorides with alkenes. Various aryl and heteroaryl chlorides were coupled efficiently under relatively mild conditions. Furthermore, this catalytic system also proved to be highly active in the Buchwald-Hartwig coupling of deactivated and sterically hindered aryl chlorides at room temperature.     

Efficient copper-free PdCl2(PCy3)2-catalyzed Sonogashira coupling of aryl chlorides with terminal alkynes

Under copper-free conditions and with Cs2CO3 as a base, PdCl2(PCy3)2 showed high catalytic activity for cross-coupling of electron-rich, electron-neutral, and electron-deficient aryl chlorides with a variety of terminal alkynes in DMSO at 100-120 degrees C affording internal arylated alkynes in good to excellent yields.     

Simple tricyclohexylphosphine-palladium complexes as efficient catalysts for the Stille coupling of deactivated aryl chlorides

Simple, inexpensive tricyclohexylphosphine adducts of palladium show the highest activity yet observed in the Stille coupling of non-activated and deactivated aryl chlorides.     

An efficient catalyst for Pd-catalyzed carbonylation of aryl arenesulfonates

Aryl carboxylic esters were synthesized by Pd-catalyzed carbonylation of aryl p-fluorobenzenesulfonates or -tosylates. A unique Josiphos ligand was discovered through high-throughput catalyst screening, which was the key for the successful carbonylation of various substrates. This catalyst is effective and works well for both electron-rich and electron-poor aryl arenesulfonates. Isolated yields of up to 90% were obtained for aryl p-fluorobenzenesulfonates and -tosylates. [reaction: see text]     

Pd-catalyzed efficient one-pot sequential cross-coupling reactions of aryl dihalides

The palladium complex containing N-heterocyclic carbene ligands catalyzes one-pot sequential Heck/Suzuki, Heck/Heck, and Heck/Sonogashira coupling reactions of aryl dihalides to afford unsymmetrically substituted arenes in excellent yields.     

Biphenylene-substituted ruthenocenylphosphine for Suzuki-Miyaura coupling of aryl chlorides

High activity in the palladium-catalyzed Suzuki-Miyaura reactions of aryl chlorides with arylboronic acids was furnished using biphenylene-substituted di- tert-butylruthenocenylphosphine (R-Phos) as a supporting ligand. Substrate combinations even for the construction of highly hindered tetra- ortho-substituted biaryls can be achieved in good to excellent yields with low catalyst loadings in short reaction times.     

Rapid, easy copper-free Sonogashira couplings using aryl iodides and activated aryl bromides

We present here an easy, rapid copper-free methodology for the Sonogashira coupling reaction. It works well for a range of aryl iodides and activated aryl bromides.     

Sonogashira coupling of aryl halides catalyzed by palladium on charcoal

With the proper choice of solvent, palladium on charcoal acts as an efficient catalyst in the Sonogashira cross-coupling reaction of aryl bromides. The catalytically active species in the process is probably palladium, which leaches into the solution but returns onto the surface of the charcoal at the end of the reaction.     

One-pot amidation of olefins through Pd-catalyzed coupling of alkylboranes and carbamoyl chlorides

A one-pot synthesis of C1-elongated amides starting from olefins and carbamoyl chlorides has been developed. Alkylboranes, generated by hydroboration of terminal olefins with 9-BBN-H, underwent smooth coupling with carbamoyl chlorides in the presence of palladium catalyst and Cs2CO3.     

Sonogashira cross-coupling reactions of aryl chlorides with alkynes catalysed by a tetraphosphine-palladium catalyst

A range of aryl chlorides undergoes cross-couplings with alkynes in good yields in the presence of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as catalyst. A variety of aryl chlorides such as chloroacetophenone, chlorobenzonitrile, chloronitrobenzene, chloroanisole or chlorotoluene have been used successfully. The reaction also tolerates several alkynes such as phenylacetylene, dec-1-yne, ethynylcyclohexene or alk-1-ynols. Furthermore, this catalyst can be used at low loading with some substrates.     

Palladium-catalyzed deacetonative coupling of aryl propargylic alcohols with aryl chlorides in water

A highly efficient and green process for palladium-catalyzed deacetonative coupling of aryl propargylic alcohols with aryl chlorides has been developed. The reaction occurs smoothly in neat water with 2?mol% PdCl₂ as catalyst, and various synthetically useful functional groups, including ether, aldehyde, ketone, and heterocyclics, are well tolerated. Moreover, the reaction could proceed through a consecutive Sonogashira/deacetonative process using 2-methyl-3-butyn-2-ol and aryl chlorides as coupling partners, affording the symmetric alkynes in good yields.