Exploration of copper and amine-free Sonogashira cross coupling reactions of 2-halo-3-alkyl imidazo[4,5-b]pyridines using tetrabutyl ammonium acetate as an activator under microwave enhanced conditions

Enhancing the reactivity of the catalytic system by using palladium catalyst with sterically demanding and electron rich ligands attached to it has often been shown as an appropriate way of performing the copper-free Sonogashira reaction. In this paper, we report PdCl₂(PCy₃)₂ as an efficient catalyst for the copper and amine-free Sonogashira cross coupling reactions of 2-halo-3-alkyl imidazo[4,5-b]pyridines (I, Br, Cl) using tetrabutyl ammonium acetate as an activator under microwave enhanced conditions.     

Heterogeneous copper-free Sonogashira coupling reaction catalyzed by a reusable palladium Schiff base complex in water

Heterogeneous Sonogashira coupling of terminal alkynes with aryl halides was studied over a polymer-supported macrocyclic Schiff base palladium complex. The cross-coupling reaction proceeded smoothly by adding a piperidine in water medium. The catalyst exhibited effective catalytic activities to afford the corresponding products in good to excellent yields under copper-free conditions. Furthermore, the catalyst could be easily recovered and reused for several times without a significant loss of its activity.     

Copper-free Sonogashira reaction using 7-chloro camptothecins

We studied copper-free Sonogashira reaction using 7-chloro camptothecins, and determined that rac-BINAP/Pd(OAc)₂ was an efficient catalyst for the coupling reaction. With this process, a number of 7-substituted camptothecins with a wide range of functional groups are potentially accessible. Besides, two drugs, SN-38 and BNP-1350, could be prepared by this method.     

Solvent-free Heck and copper-free Sonogashira cross-coupling reactions catalyzed by a polystyrene-anchored Pd(II) phenyldithiocarbazate complex

A new polystyrene-anchored Pd(II) phenyldithiocarbazate complex is synthesized and characterized. This Pd-complex behaves as an efficient heterogeneous catalyst in the Heck coupling and copper-free Sonogashira coupling reactions under aerobic conditions. Furthermore, the catalyst shows good thermal stability and recyclability.     

Copper-free Sonogashira coupling reactions catalyzed by a water-soluble Pd-salen complex under aerobic conditions

The water-soluble Pd-salen complex, palladium(II) N,N′-bis{[5-(triphenylphosphonium)methyl]salicylidene}-1,2-ethanediamine chloride, is a highly active catalyst for the copper-free Sonogashira coupling of aryl iodides with terminal alkynes in water under aerobic conditions.     

A diphenylphosphinoethane-functionalized polystyrene resin-supported Pd(0) complex as an effective catalyst for copper-free Sonogashira coupling reactions under aerobic conditions

A polymer-supported palladium(0) diphenylphosphinoethane complex was found to be a highly active catalyst for the copper-free Sonogashira coupling reaction of aryl iodides with terminal alkynes, giving excellent yields of products (85-98%) under aerobic conditions.     

Photo-activation of Pd-catalyzed Sonogashira coupling using a Ru/bipyridine complex as energy transfer agent

The mixed catalyst system, Pd(CH3CN)2Cl2/P(t-Bu)3/[Ru(2,2'-bipyridine)3].2PF6, promotes the copper-free Sonogashira coupling reaction of aryl bromides at room temperature under irradiation of visible light.     

Enhanced catalyst recovery in an aqueous copper-free Sonogashira cross-coupling reaction

We report the synthesis of a superparamagnetic nanoparticle MNP (γ-Fe(2)O(3)/polymer) supported dendritic catalyst based on a bulky electron-rich phosphine Pd(II) complex. The high reactivity of this catalyst is described in a copper-free Sonogashira C-C cross-coupling reaction in water, and the significant role of surfactant additives is highlighted in the recovery study.     

Cyclopalladated ferrocenylimines: efficient catalysts for homocoupling and Sonogashira reaction of terminal alkynes

A novel pathway for homocoupling of terminal alkynes has been described using cyclopalladated ferrocenylimine 1 or 2/CuI as catalyst in the air. This catalytic system could tolerate several functional groups. The palladacycle 2 in the presence of n-Bu₄NBr as an additive could be applied to Sonogashira cross-coupling reaction of aryl iodides, aryl bromides, and some activated aryl chlorides with terminal alkynes under amine- and copper-free conditions, mostly to give moderate to excellent yields.     

Biginelli reaction beyond three-component limit: synthesis of functionalized pyrimidinones via a one-pot Biginelli-Pd mediated C-C coupling strategy

A new and one-pot synthesis of novel alkynyl/alkenyl/aryl (hetero)aryl substituted 3,4-dihydropyrimidin-2(1H)-one derivatives has been developed via a multi-component reaction involving sequential phosphorus acid-mediated solvent-free Biginelli followed by copper-free Sonogashira or Heck or Suzuki reaction.     

Microwave assisted copper-free Sonogashira coupling/5-exo-dig cycloisomerization domino reaction: access to 3-(phenylmethylene)isoindolin-1-ones and related heterocycles

An efficient microwave assisted one-pot synthesis of substituted 3-(phenylmethylene)isoindolin-1-ones is reported via a copper-free Sonogashira coupling and a regioselective 5-exo-dig cycloisomerization. This domino reaction was also extended to other related heterocycles.     

Efficient and general protocol for the copper-free sonogashira coupling of aryl bromides at room temperature

[reaction: see text]. A mild and general protocol for the copper-free Sonogashira coupling of aryl bromides with acetylenes has been developed. The use of (AllylPdCl)2 and P(t-Bu)3 provides the active Pd(0) catalyst that allows subsequent coupling of various alkynes at room temperature with good to excellent yields.     

Copper-Free Sonogashira coupling in water with an amphiphilic resin-supported palladium complex

The palladium-catalyzed coupling reaction of aryl halides with terminal alkynes, the Sonogashira coupling, took place in water under copper-free conditions by use of an amphiphilic polystyrene-poly(ethylene glycol) (PS-PEG) resin-supported palladium-phosphine complex to give the corresponding aryl-substituted alkynes in high yields. The PS-PEG resin-supported palladium catalyst was recovered by simple filtration and reused four times without any loss of catalytic activity.     

Sonogashira cross-coupling reactions catalysed by heterogeneous copper-free Pd-zeolites

A heterogeneous [Pd(NH₃)₄]-NaY catalyst was applied to the copper-free Sonogashira cross-coupling of aryl halides with terminal alkynes. This copper-free heterogeneous Pd-catalyst is efficient, stable and recyclable. Aryl iodides and activated aryl bromides were converted quantitatively using 1 mol % Pd-catalyst to the corresponding diaryl-substituted alkynes within 3 h.     

Synthesis of substituted acetylenes, aryl-alkyl ethers, 2-alkene-4-ynoates and nitriles using heterogeneous mesoporous Pd-MCM-48 as reusable catalyst

Pd-MCM-48 has been employed as a heterogeneous catalyst for the synthesis of substituted acetylenes via Sonogashira reactions under copper and amine-free reaction conditions. In addition, the catalyst exhibited excellent regioselectivity for primary alcohols towards C-O coupling leading to formation of alkyl-aryl ethers in high yields. A green procedure for the stereoselective synthesis of 2-alkene-4-ynoates and nitriles from the reactions of vic-(E)-diiodoalkenes with activated alkenes has also been demonstrated using Pd-MCM-48 catalyst. The catalyst was easily recovered from the reaction mixture by filtration and reused for at least six times with minimal loss of activity.     

Pd(OAc)_2/TBAB催化卤代芳烃与末端炔烃的Sonogashira交叉偶联反应研究

研究了无铜、无配体、可回收利用的催化体系[Pd(OAc)2/TBAB]催化卤代芳烃与末端炔烃的Sonogashira交叉偶联反应,高产率地合成了一系列偶联产物,其结构经1H NMR和13C NMR表征。催化实验结果表明,Pd(OAc)2/TBAB可回收重复使用3次,催化活性基本不变。     

Copper-free Sonogashira cross-coupling for functionalization of alkyne-encoded proteins in aqueous medium and in bacterial cells

Bioorthogonal reactions suitable for functionalization of genetically or metabolically encoded alkynes, for example, copper-catalyzed azide-alkyne cycloaddition reaction ("click chemistry"), have provided chemical tools to study biomolecular dynamics and function in living systems. Despite its prominence in organic synthesis, copper-free Sonogashira cross-coupling reaction suitable for biological applications has not been reported. In this work, we report the discovery of a robust aminopyrimidine-palladium(II) complex for copper-free Sonogashira cross-coupling that enables selective functionalization of a homopropargylglycine (HPG)-encoded ubiquitin protein in aqueous medium. A wide range of aromatic groups including fluorophores and fluorinated aromatic compounds can be readily introduced into the HPG-containing ubiquitin under mild conditions with good to excellent yields. The suitability of this reaction for functionalization of HPG-encoded ubiquitin in Escherichia coli was also demonstrated. The high efficiency of this new catalytic system should greatly enhance the utility of Sonogashira cross-coupling in bioorthogonal chemistry.     

9-fluorenylphosphines for the Pd-catalyzed sonogashira, suzuki, and Buchwald-Hartwig coupling reactions in organic solvents and water

The lithiation/alkylation of fluorene leads to various 9-alkyl-fluorenes (alkyl=Me, Et, iPr, -Pr, -C18H25) in>95% yields, for which lithiation and reaction with R2PCl (R=Cy, iPr, tBu) generates 9-alkyl, 9-PR2-fluorenes which constitute electron-rich and bulky phosphine ligands. The in-situ-formed palladium-phosphine complexes ([Na2PdCl4], phosphonium salt, base, substrates) were tested in the Sonogashira, Suzuki, and Buchwald-Hartwig reactions of aryl chlorides and aryl bromides in organic solvents. The Sonogashira coupling of aryl chlorides at 100-120 degrees C leads to>90% yields with 1 mol% of Pd catalyst. The Suzuki coupling of aryl chlorides typically requires 0.05 mol% of Pd catalyst at 100 degrees C in dioxane for quantitative product formation. To carry out "green" cross-coupling reactions in water, 9-ethylfluorenyldicyclohexylphosphine was reacted in sulphuric acid to generate the respective 2-sulfonated phosphonium salt. The Suzuki coupling of activated aryl chlorides by using this water-soluble catalyst requires only 0.01 mol% of Pd catalyst, while a wide range of aryl chlorides can be quantitatively converted into the respective coupling products by using 0.1-0.5 mol% of catalyst in pure water at 100 degrees C. Difficult substrate combinations, such as naphthylboronic acid or 3-pyridylboronic acid and aryl chlorides are coupled at 100 degrees C by using 0.1-0.5 mol% of catalyst in pure water to obtain the respective N-heterocycles in quantitative yields. The copper-free aqueous Sonogashira coupling of aryl bromides generates the respective tolane derivatives in>95% yield.     

High throughput evaluation of the production of substituted acetylenes by the Sonogashira reaction followed by the Mizoroki-Heck reaction in ionic liquids, in situ, using a novel array reactor

The parallel Sonogashira coupling reaction was carried out under copper-free condition by integrating the advantages of ionic liquids as the reaction media followed by the simultaneous-multiple Mizoroki-Heck reaction in situ by the use of a novel array reactor (SynArray-24). The device provides rapid evaluation of reactions in a short period.     

Carbonylative Sonogashira annulation sequence: One-pot synthesis of 4-quinolone and 4H-chromen-4-one derivatives

Carbonylative Sonogashira annulation sequence for one pot synthesis of 4-quinolone and 4H-chromen-4-one has been developed in presence of Pd-NHC catalyst. Substituted 2-iodoaniline and 2-iodophenol independently underwent in the carbonylative Sonogashira annulation reaction with a variety of acetylenes to result in 4-quinolone and flavone derivatives respectively in good to excellent yield. Moreover, this protocol does not require toxic CO gas, high catalyst loading and any expensive salt/additive. Herein we, for the first time, are using Mo(CO)₆, as solid CO source for the one pot synthesis of flavone derivatives via carbonylative Sonogashira annulation reaction.