Sulfonated N‐Heterocyclic Carbenes for Pd‐Catalyzed Sonogashira and Suzuki–Miyaura Coupling in Aqueous Solvents

The reactions of the N,N′‐diarylimidazolium and N,N′‐diarylimidazolinium salts with chlorosulfonic acid result in the formation of the respective disulfonated N‐heterocyclic carbene (NHC) precursors in reasonable yields (46–77%). Water‐soluble palladium catalyst complexes, in situ obtained from the respective sulfonated imidazolinium salt, sodium tetrachloropalladate (Na₂PdCl₄) and potassium hydroxide (KOH) in water, were successfully applied in the copper‐free Sonogashira coupling reaction in isopropyl alcohol/water mixtures using 0.2 mol% catalyst loading. The preformed (disulfonatedNHC)PdCl(cinnamyl) complex was used in aqueous Suzuki–Miyaura reactions at 0.1 mol% catalyst loading. The coupling protocol reported here is very useful for Sonogashira reactions of N‐ and S‐heterocyclic aryl bromides and chlorides with aryl‐ and alkylacetylenes.     

Synthesis of Well‐Defined Diphenylvinyl(cyclopropyl)phosphine‐Palladium Complexes for the Suzuki–Miyaura Reaction and Buchwald–Hartwig Amination

The well‐defined diphenylvinylphosphine‐palladium complex 1 and the diphenylcyclopropylphosphine‐palladium complex 2 were successfully synthesized. The crystal structures of these complexes were obtained by X‐ray crystallographic analysis. Both complexes were air‐ and moisture‐stable, and could be prepared on a gram scale. These palladium complexes catalyzed the Suzuki–Miyaura reaction of aryl bromides [turnover numbers (TON) up to 196,000] and aryl chlorides (TON up to 50,000). Furthermore, complex 2 catalyzed the Buchwald–Hartwig amination of aryl chlorides and aromatic/aliphatic amines with a low catalyst loading. These complexes showed different reactivities for the coupling of 2‐chloropyridine, and the origin of this difference is discussed.     

Palladium‐Catalyzed Efficient and One‐Pot Synthesis of Diarylacetylenes from the Reaction of Aryl Chlorides with 2‐Methyl‐3‐butyn‐2‐ol

An efficient and practical synthetic method has been developed for the preparation of symmetrical diarylacetylenes from the direct reaction of aryl chlorides with 2‐methyl‐3‐butyn‐2‐ol catalyzed by palladium(II) chloride‐bis(tricyclohexylphosphine) [PdCl₂(PCy₃)₂] under mild reaction conditions. Unsymmetrical diarylated acetylenes could be also obtained by using two different aryl chlorides simultaneously. The catalytic procedure includes a novel one‐pot palladium‐catalyzed, double Sonogashira coupling of inactivated aryl chlorides without use of copper(I) as co‐catalyst.     

Palladium Nanoparticles Immobilized on Nano‐Silica Triazine Dendritic Polymer (Pdnp‐nSTDP): An Efficient and Reusable Catalyst for Suzuki–Miyaura Cross‐Coupling and Heck Reactions

A new catalyst based on palladium nanoparticles immobilized on nano‐silica triazine dendritic polymer (Pd_np‐nSTDP) was synthesized and characterized by FT‐IR spectroscopy, thermogravimetric analysis, field emission scanning electron microscopy, energy dispersive X‐ray, transmission electron microscopy and elemental analysis. The size of the palladium nanoparticles was determined to be 3.1±0.5 nm. This catalytic system showed high activity in the Suzuki–Miyaura cross‐coupling of aryl iodides, bromides and chlorides with arylboronic acids and also in the Heck reaction of these aryl halides with styrenes. These reactions were best performed in a dimethylformamide (DMF)/water mixture (1:3) in the presence of only 0.006 mol% and 0.01 mol% of the catalyst, respectively, under conventional conditions and microwave irradiation to afford the desired coupling products in high yields. The Pd_np‐nSTDP was also used as an efficient catalyst for the preparation of a series of star‐ and banana‐shaped compounds with a benzene, pyridine, pyrimidine or 1,3,5‐triazine unit as the central core. Moreover, the catalyst could be recovered easily and reused several times without any considerable loss of its catalytic activity.     

Mizoroki–Heck Reactions Catalyzed by Dichloro{bis[1‐(dicyclohexylphosphanyl)piperidine]}palladium: Palladium Nanoparticle Formation Promoted by (Water‐Induced) Ligand Degradation

The palladium‐based dichlorobis[1‐(dicyclohexylphosphanyl)piperidine] complex – [(P{(NC₅H₁₀)(C₆H₁₁)₂})₂Pd(Cl)₂] is readily prepared in quantitative yield from the reaction of [Pd(cod)(Cl)₂] (cod=cycloocta‐1,5‐diene) with two equivalents of 1‐(dicyclohexylphosphanyl)piperidine in toluene under N₂ within only a few minutes at room temperature. This complex is a highly active Heck catalyst with excellent functional group tolerance, which reliably operates at low catalyst loadings. Various activated, non‐activated, deactivated, functionalized, sterically hindered, and heterocyclic aryl bromides, which may contain nitro, chloro or trifluoromethane groups, nitriles, acetales, ketones, aldehydes, ethers, esters, lactones, amides, anilines, phenols, alcohols, carboxylic acids, and heterocyclic aryl bromides, such as pyridines and derivatives, as well as thiophenes and aryl bromides containing methylsulfanyl groups have been successfully coupled with various (also functionalized) alkenes in excellent yields and selectivities (the E‐isomers are typically exclusively formed) at 140 °C in the presence of 0.05 mol % of the catalyst in DMF. Even though lower catalyst loadings could be used for many electronically activated, non‐activated and some electronically deactivated aryl bromides without noticeable loss of activity, the great advantage of the reaction protocol presented here lies in its reliability and general applicability, which allows its direct adoption to other aryl bromides without the neccessity of its modification. Experimental observations indicated that palladium nanoparticles are the catalytically active form. Consequently, whereas comparable levels of activity were observed for dichloro‐bis(aminophosphine) complexes of palladium, a dramatic drop in activity was found for their phosphine‐based analogue [(P(C₆H₁₁)₃)₂Pd(Cl)₂].     

Palladium on Carbon‐Catalyzed Cross‐Coupling using Triarylbismuths

Simple and efficient protocols for the 10% palladium on carbon (Pd/C)‐catalyzed cross‐coupling reactions between triarylbismuths and aryl halides have been developed. A variety of iodo‐ and bromobenzenes possessing an electron‐withdrawing group on the aromatic nucleus were smoothly cross‐coupled in the presence of 10% Pd/C, sodium phosphate dodecahydrate (Na₃PO₄⋅12 H₂O) and 1,4‐diazabicyclo[2.2.2]octane (DABCO) in heated N‐methyl‐2‐pyrrolidone (NMP) as the solvent. For the arylations of iodobenzenes, the reactions effectively proceeded under the combined use of caesium fluoride (CsF) and 2,2′‐biquinoline. Furthermore, a ligand‐free 10% Pd/C‐catalyzed cross‐coupling reaction between the aryl iodides and triarylbismuths was also established by the addition of tetra‐n‐buthylammonium fluoride trihydrate (TBAF⋅3 H₂O) in which the palladium metals were hardly leached from the catalyst into the reaction media.     

Palladium(II)‐Catalyzed 1,4‐Addition of Arylboronic Acids to β‐Arylenones for Enantioselective Synthesis of 4‐Aryl‐4H‐chromenes

The enantioselective 1,4‐addition of arylboronic acids to β‐arylenones to give β‐diaryl ketones was carried out at 0–25 °C in the presence of a dicationic palladium(II) catalyst, [Pd(S,S‐chiraphos)(PhCN)₂](SbF₆)₂. Addition of a silver salt such as silver tetrafluoroborate [AgBF₄] or silver hexafluoroantimonate [AgSbF₆] (5–10 mol %) was effective to achieve high enantioselectivities at low temperatures (92–99 % ee) and to reduce the catalyst loading to 0.05 mol %. The protocol provided a simple access to 4‐aryl‐4H‐chromenes. Optically active chromenes were synthesized with up to 99 % ee via dehydration of the 1,4‐adducts between arylboronic acids and β‐(2‐hydroxyaryl)‐α,β‐unsaturated ketones.     

Regioselective Heck Reaction of N‐Vinylphthalimide: A General Strategy for the Synthesis of (E)‐N‐Styrylphthalimides and Phenethylamines

The arylation of N‐vinylphthalimide takes place at the β‐position with aryl iodides, bromides and chlorides using palladium acetate [Pd(OAc)₂] or phenone oxime‐derived palladacycles as catalysts under phosphine‐free conditions. The reaction is succesfully carried out in organic solvents, such as DMF, in the presence of an organic base, such as dicyclohexylmethylamine, and with TBAB as additive at 120 °C under conventional or microwave heating. (E)‐N‐Styrylphthalimides are mainly obtained using a rather low palladium loading (0.05–1 mol%). Similar catalytic efficiency is observed using a Kaiser oxime resin‐derived palladacycle, which allows reuse of the polymeric complex for three cycles. The high regioselectivity observed supports that these palladacycles work as a source of Pd(0) species operating mainly through a neutral mechanism. The syntheses of 2‐thienylphenethylamine and mescaline have been performed by subsequent hydrogenation with Wilkinson’s catalyst and hydrazinolysis.     

Heterogeneous Palladium Catalysts Applied to the Synthesis of 2‐ and 2,3‐Functionalised Indoles

Heterogeneous palladium catalysts ([Pd(NH₃)₄]²⁺/NaY and [Pd]/SBA‐15) were applied to the synthesis of 2‐functionalised indoles, giving generally high conversions and selectivities (>89% yield) using only 1 mol % [Pd]‐catalyst under standard reaction conditions (polar solvent, 80 °C). For the synthesis of 2,3‐functionalised indoles by cross‐coupling arylation, the [Pd]/SBA‐15 catalyst was found to be particularly interesting, producing the expected compound with =35% yield after 12 days of reaction, which is comparable to the homogeneous catalyst, Pd(OAc)₂ (=48% yield). In the course of the study, the dual reactivity of the indole nucleus was demonstrated: aryl bromides gave clean C C coupling while aryl iodides led to a clean C N coupling.     

Palladium‐Catalyzed,Highly Efficient,Regiocontrolled Arylation of Electron‐Rich Allylamines with Aryl Halides

The highly efficient and regioselective palladium‐catalyzed Heck coupling of aryl bromides with electron‐rich allylamine derivatives is described. It was found that the choice of solvent, olefin, ligand and additive had a fundamental influence on the regioselectivity and reactivity of the reaction. The combination of palladium acetate [Pd(OAc)₂] and 1,3‐bis(diphenylphosphino)propane (dppp) in ethylene glycol (EG) constitutes a highly effective catalyst system for internal arylation of N‐Boc‐allylamine (tert‐butyl methyl allyliminodicarbonate) with aryl bromides to give good to excellent regioselectivities, while the catalyst system consisting of Pd(OAc)₂, tetrabutylammonium bromide (TBAB) and 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) additive allows for a variety of aryl bromides to react efficiently with N,N‐(Boc)₂‐allylamine (di‐tert‐butyl allyliminodicarbonate) in water to exclusively afford the linear (E)‐allylamine products in high yields.     

Calixarene‐Derived Mono‐Iminophosphoranes: Highly Efficient Ligands for Palladium‐ and Nickel‐Catalysed Cross‐Coupling

The first mono‐iminophosphoranes based on a calix[4]arene skeleton have been synthesised and tested in the arylation of aryl bromides and aryl chlorides. Combining these ligands with [Pd(OAc)₂] or [Ni(cod)₂] resulted in highly active Suzuki–Miyaura and Kumada–Tamao–Corriu cross‐coupling catalysts, respectively. TOFs up to ca. 4×10⁵ mol(ArBr)⋅mol(M)⁻¹⋅h⁻¹ were obtained in each case. The remarkable activities observed probably arise from the ligands’ ability to form complexes with cavity‐entrapped “MArX” moieties (endo‐complexes), their highly crowded metal environment favouring formation of mono‐ligated intermediates over that of less reactive bis‐ligated ones. Possible supramolecular interactions within the cavity involving the receptor wall and the aromatic substrate may also significantly influence the reaction rates, notably by increasing the proportion of endo‐complexes.     

Oxadiazoline and Ketoimine Palladium(II) Complexes as Highly Efficient Catalysts for Suzuki–Miyaura Cross‐Coupling Reactions in Supercritical Carbon Dioxide

The [2+3] cycloaddition of nitriles (RCN) with 2,2‐dimethyl‐3,4‐dihydro‐2H‐pyrrole 1‐oxide, in the presence of palladium dichloride (PdCl₂) gives the corresponding 2,3‐dihydro[1.2.4]oxadiazole (Δ⁴‐1,2,4‐oxadiazoline) palladium(II) complexes 1 – 4 in good yields. However, the Pd(II)‐assisted reaction of pentafluorobenzonitrile with the same pyrroline N‐oxide gives a mixture of oxadiazoline 5 , ketoimine 6 and pyrrolylbenzamide‐ketoimine 7 Pd(II) complexes, which affords upon heating in refluxing acetone the unprecedented fused tricyclic ketoimine complex 8 as the exclusive product. Under heating, compounds 5 and 7 transform to 6 , the latter undergoing intramolecular cyclization by nucleophilic attack of the amino moiety to the ortho carbon of the pentafluorophenyl ring leading ultimately to 8 . The compounds were characterized by IR, ¹H and ¹³C NMR, ESI⁺‐MS, elemental analyses and, in the cases of 3 , 6 , 7 and 8 , also by X‐ray diffraction analyses. The catalytic properties of the Pd complexes were evaluated in Suzuki–Miyaura cross‐coupling reactions, using supercritical carbon dioxide (scCO₂) as a green solvent. Cross‐couplings of aryl halides with phenylboronic acid give the desired biaryl products in quantitative yields, in a short reaction time, for substrate‐to‐catalyst molar ratios as high as 4.0⋅10⁴.     

Synthesis of Methylene‐Bridge Polyarenes through Palladium‐Catalyzed Activation of Benzylic Carbon‐Hydrogen Bond

In the presence of palladium(II) acetate [Pd(OAc)₂] and an N‐heterocyclic carbene (NHC) ligand, fluorene derivatives can be generated in good to excellent yields from 2‐halo‐2′‐methylbiaryls through the benzylic C H bond activation (14 examples; 81–97% yields). The scope and limitations of this protocol have been examined. A wide range of functional groups, such as alkyl, alkoxy, ester, nitrile, and others, is able to tolerate the reaction conditions herein. The cyclization of an isotope‐labelled biphenyl gave the corresponding product with a primary kinetic isotope effect (k_H/k_D=4.8:1), which indicates that the rate‐determining step of this reaction is the activation of the benzylic C H bond. Moreover, indenofluorenes were also accessed in excellent results from terphenyls (3 examples; 91–92% yields). The cascade reaction of 2,6‐dichloro‐2′‐methylbiphenyl with diphenylacetylene produced 8,9‐diphenyl‐4H‐cyclopenta[def]phenanthrene in 60% yield through the activation of an aryl and a benzylic C H bond.     

Suzuki–Miyaura Reactions of Aryl Chloride Derivatives with Arylboronic Acids using Mesoporous Silica‐Supported Aryldicyclohexylphosphine

The Suzuki–Miyaura reactions using mesoporous‐supported aryldicyclohexylphosphine as ligand have been investigated. The catalysts were based on SBA‐15 type mesoporous silica which was transformed in a four‐step synthesis leading to a phosphine‐containing hybrid material The most productive catalytic system studied was generated in situ from this material and the homogeneous palladium complex, Pd(OAc)₂. Other catalytic systems were studied for comparison [homogeneous cataysts, a “preformed” catalyst obtained by reaction of PdCl₂(PhCN)₂ and the phosphine‐containing material]. Variations involving the solvent system, the substrate aryl chloride and the arylboronic acid reactant were also studied. For both in situ and preformed catalyst systems, high conversions and yields are obtained for activated aryl chlorides. Success of the reaction for unactivated aryl chlorides was limited to the catalyst formed in situ. The catalyst formed in situ was also shown to be reactive under aqueous reaction conditions in the cross‐coupling of 1‐(4‐chlorophenyl)ethanone with phenylboronic acid.     

Ligand‐Free Buchwald–Hartwig Aromatic Aminations of Aryl Halides Catalyzed by Low‐Leaching and Highly Recyclable Sulfur‐Modified Gold‐Supported Palladium Material

A stable heterogeneous catalyst precursor, sulfur‐modified gold‐supported palladium material (SAPd), has proved to be an excellent source of leached, ligand‐free, Pd for the amination of aryl bromides and chlorides. The reaction‐enabling catalyst is provided in situ as leached Pd in low catalyst loading (0.21±0.02 mol%). This allows the precatalyst (SAPd) to be filtered off and used for a minimum of ten reaction cycles without loss of catalytic activity. SAPd released only trace amounts, less than 0.6 ppm, of highly active Pd during the reaction without any aggregation.     

The First Fluoride‐Free Hiyama Reaction of Vinylsiloxanes Promoted by Sodium Hydroxide in Water

The first cross‐coupling reaction between vinylalkoxysilanes and aryl bromides or chlorides promoted by aqueous sodium hydroxide under fluoride‐free conditions to provide styrenes is reported. The reaction is catalyzed by palladium(II) acetate or a 4‐hydroxyacetophenone oxime‐derived palladacycle either under thermal or microwave heating at 120 °C with low catalyst loading (0.01–1 mol % of palladium) in the presence of tetra‐n‐butylammonium bromide (TBAB) as additive in air. In the case of styryltriethoxysilane, the coupling with aryl or vinyl bromides takes place stereospecifically to give the corresponding stilbenes or dienes, respectively. These mild and simple reaction conditions prevent undesirable polymerization of the products.     

Electronegativity Governs Enantioselectivity: Alkyl‐Aryl Cross‐Coupling with Fenchol‐Based Palladium‐Phosphorus Halide Catalysts

A series of bulky, modular, monodentate, fenchol‐based phosphites has been employed in an intramolecular palladium‐catalyzed alkyl‐aryl cross‐coupling reaction. This enantioselective α‐arylation of N‐(2‐bromophenyl)‐N‐methyl‐2‐phenylpropanamide is accomplished with [Pd(C₃H₅)(BIFOP‐X)(Cl)] as precatalysts, which are based on biphenyl‐2,2′‐bisfenchol phosphites (BIFOP‐X, X=F, Cl, Br, etc.). The phosphorus fluoride BIFOP‐F gives the highest enantioselectivity and good yields (64% ee, 88%). Lower selectivities and yields are found for BIFOP halides with heavier halogens (Cl: 74%, 47% ee, Br: 63%, 20% ee). NMR studies on catalyst complexes reveal two equilibrating diastereomeric complexes in equal proportions. In all cases, the phosphorus‐halogen moiety remains intact, pointing to its remarkable stability, even in the presence of nucleophiles. The increasing enantioselectivity of the catalysts with the phosphorus halide ligands correlates with the rising electronegativity of the halide (bromine<chlorine<fluorine), as can be rationalized from structural parameters and DFT computations.     

Functionalized cellulose‐supported triphenylphosphine and its application in Suzuki cross‐coupling reactions

A new heterogeneous cellulose tagged triphenylphosphine (Cell‐OPPh₃) was synthesized and subsequently coordinated with Pd(OAc)₂ to form a cellulose‐supported triphenylphosphine palladium complex (Cell‐OPPh₃‐Pd). Cell‐OPPh₃ and the corresponding palladium complex were fully characterized by TGA, SEM, TEM, and NMR analysis. Results of catalytic activity experiments indicate that the Cell‐OPPh₃‐Pd complex can efficiently catalyze Suzuki–Miyaura cross‐coupling reactions of aryl halides with arylboronic acids at mild reaction conditions. The coupling products can be obtained in good to excellent yields (up to 98%). The work‐up procedure is simple and the catalyst could be easily recovered by filtration, and then reused in next run. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41427.     

Practical Synthesis of 2‐Arylacetic Acid Esters via Palladium‐ Catalyzed Dealkoxycarbonylative Coupling of Malonates with Aryl Halides

A new palladium‐based system was developed that catalyzes the coupling of aryl halides with diethyl malonates in the presence of mild bases. In the course of the reaction, the intermediately formed diethyl arylmalonate is directly converted into the arylacetic acid ester via liberation of carbon dioxide and an alkanol. This cross‐coupling/dealkoxycarbonylation process provides an efficient and high‐yielding synthetic entry to diversely functionalized arylacetic acid esters. Two complementary protocols were developed, one of which is optimal for electron‐rich, the other for electron‐poor aryl halides. Both make use of low loadings of palladium(0) bis(dibenzylideneacetone) (0.5 mol%)/tri‐tert‐butylphosphonium tetrafluoroborate (1.1 mol%) as the catalyst and diethyl malonate as the reaction solvent. The new procedures are particularly effective for sterically hindered substrates.     

Development of Structurally Diverse N‐Heterocyclic Carbene Ligands via Palladium‐Copper‐Catalyzed Decarboxylative Arylation of Pyrazolo[1,5‐a]pyridine‐3‐carboxylic Acid

A series of fused non‐classical normal N‐heterocyclic carbenes, Pyrpy‐NHC precursors derived from pyrazolo[1,5‐a]pyridines, has been prepared using palladium‐copper‐catalyzed decarboxylative arylation of pyrazolo[1,5‐a]pyridine‐3‐carboxylic acid. Air‐stable palladium and rhodium complexes of these ligands have been synthesized via mild transmetallation of Ag‐Pyrpy‐NHC. The structural properties of Rh(Pyrpy‐NHC)(COD)Cl complexes were determined via X‐ray analysis. The measurement of the CO stretching frequencies of dicarbonyl Rh‐Pyrpy‐NHC complexes revealed that the electron donating strength of Pyrpy‐NHC could be tuned by varying the substituents of the aryl group. A catalytic study of the Pd‐Pyrpy‐NHC complexes revealed promising activity in the Suzuki–Miyaura reaction under ambient atmospheric conditions.