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.     

Highly Efficient Suzuki Cross‐Coupling Catalyzed by Palladium/Phosphine‐Imidazolium Carbene System

Novel phosphine‐imidazolium salts 2 have been synthesized and successfully used in palladium‐catalyzed Suzuki cross‐coupling. A combination of 0.05 mol % of [Pd(η‐C₃H₅)Cl]₂ and 0.1 mol % of 2b in the presence of 2 equivs. of K₃PO₄ as base provided coupling products in excellent yields in the reaction of aryl bromides and chlorides with aryl boronic acids.     

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.     

Hybrid Organic‐Inorganic Materials from Di‐(2‐pyridyl)methylamine‐Palladium Dichloride Complex as Recoverable Catalysts for Suzuki,Heck and Sonogashira Reactions

Hybrid silica materials containing the di‐(2‐pyridyl)methylamine‐palladium dichloride complex, prepared by sol‐gel cogelification, are efficient recyclable catalysts for Suzuki (aryl bromides and chlorides), Heck (aryl bromides) and Sonogashira reactions (aryl iodides and bromides). Formation of palladium(0) nanoparticles is observed in the Suzuki and Heck reactions but not in the Sonogashira coupling.     

The Synthesis of Important Pharmaceutical Building Blocks by Palladium‐Catalyzed Coupling Reaction: Access to Various Arylhydrazines

Various arylhydrazones have been successfully synthesized via a highly efficient palladium‐catalyzed cross‐coupling reaction between aryl halides and benzophenone hydrazone. All the reaction parameters have been studied and coupling products were obtained with excellent yields from the corresponding bromides or chlorides.     

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.     

A Novel (2,2‐Diarylvinyl)phosphine/Palladium Catalyst for Effective Aromatic Amination

A new series of diarylvinylphosphine ligands was designed and synthesized. A catalyst system, consisting of the ligands and palladium species, effectively catalyzed the coupling reaction of aryl bromides and chlorides with amines to afford the corresponding products in good to excellent yields. The efficiency is likely derived from an interaction between the palladium center and the cis‐aryl moiety on the diarylvinylphosphine ligand stabilizing a catalytic intermediate during the coupling reaction.     

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.     

A General and Practical Palladium‐Catalyzed Direct α‐Arylation of Amides with Aryl Halides

An efficient system for the direct catalytic intermolecular α‐arylation of acetamide derivatives with aryl bromides and chlorides is presented. The palladium catalyst is supported by Kwong’s indole‐based phosphine ligand and provides monoarylated amides in up to 95% yield. Excellent chemoselectivities (>10:1) in the mono‐ and diarylation with aryl bromides were achieved by careful selection of bases, solvents, and stoichiometry. Under the coupling conditions, the weakly acidic α‐protons of amides (pK_a up to 35) were reversibly depotonated by lithium tert‐butoxide (LiO‐t‐Bu), sodium tert‐butoxide (NaO‐t‐Bu) or sodium bis(trimethylsilyl)amide [NaN(SiMe₃)₂].

     

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.     

Simple Methodology for Heck Arylation at C‐8 of Adenine Nucleosides

A simple method for the arylation of 8‐vinyladenine nucleoside derivatives is reported. With a broad set of aryl iodides and bromides, the reaction is catalyzed by the simple combination palladium acetate/tris(o‐tolyl)phosphine/triethylamine [Pd(OAc)₂/(o‐tol)₃P/Et₃N]. As expected, aryl chlorides are more difficult coupling partners but some undergo reactions with more exotic catalysts. Although trans‐olefins are the major products, minor amounts of cis‐isomers are detected in some cases, and a post‐arylation mechanism for their formation is proposed. Finally, by subtle catalyst modulation chemoselective N‐arylation of the nucleoside can be achieved in the presence of the vinyl moiety.     

Synthesis of Amido‐N‐imidazolium Salts and their Applications as Ligands in Suzuki–Miyaura Reactions: Coupling of Hetero‐ aromatic Halides and the Synthesis of Milrinone and Irbesartan

A new catalytic system based on palladium‐amido‐N‐heterocyclic carbenes for Suzuki–Miyaura coupling reactions of heteroaryl bromides is described. A variety of sterically bulky, amido‐N‐imidazolium salts were synthesized in high yields from the corresponding anilines. This catalytic system effectively promoted Suzuki–Miyaura couplings of heteroaryl bromides and chlorides with a range of boronic acids to give the corresponding aryl compounds in high yield. The yield was increased with increasing steric bulkiness of the substituted group. Especially, 1‐(2,6‐diisopropylphenyl)‐3‐N‐(2,4,6‐tri‐tert‐butylphenylacetamido)imidazolium bromide ( 4bc ) exhibited 850,000 TON in the coupling reaction of 2‐bromopyridine and phenylboronic acid. In addition, pharmaceutical compounds such as milrinone and irbesartan were synthesized via Suzuki–Miyaura coupling using sterically bulky, amido‐N‐imidazolium salt ( 4bc ) as a ligand.     

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.     

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.     

A Highly Efficient Palladium‐Catalyzed One‐Pot Synthesis of Unsymmetrical Aryl Alkyl Thioethers under Mild Conditions in Water

A palladium‐catalyzed, one‐pot synthesis of unsymmetrical aryl alkyl thioethers involving aryl halides (aryl bromides and chlorides), thiourea and alkyl bromides has been realized under mild conditions (room temperature to 50 °C) in water with polyoxyethanyl α‐tocopheryl sebacate (PTS) as amphiphile. The PTS/water could be recycled in up to eight runs without an obvious change in its activity.     

Suzuki–Miyaura Cross‐Coupling under Solvent‐Free Conditions

A solvent‐free reaction protocol for Suzuki–Miyaura cross‐couplings was developed. (Hetero)aryl bromides and chlorides are coupled with pinacol arylboronates in high yields. The reaction is catalyzed by conventional bis(triphenylphosphine)palladium(II) chloride [(PPh₃)₂PdCl₂] and/or palladium(II) acetate/SPhos [Pd(OAc)₂/SPhos] under air.

     

Palladium Nanoparticles in Suzuki Cross‐Couplings: Tapping into the Potential of Tris‐Imidazolium Salts for Nanoparticle Stabilization

Inspired by the proclivity of various palladium sources to form nanoparticles in imidazolium‐based ionic liquids, we now report that tris‐imidazolium salts bearing hexadecyl chains and a bridging mesitylene moiety are potent stabilizers of palladium nanoparticles efficiently prepared via a Chaudret‐type hydrogenation of the bis(dibenzylideneacetone)palladium(0). The palladium nanoparticles have been isolated in pure form and characterized by ¹H nuclear magnetic resonance, transmission electron microscopy, electron diffraction and dynamic light scattering. The new materials proved effective in Suzuki cross‐coupling at a loading of 0.2% palladium. Thus, using a tris‐imidazolium iodide‐palladium material, a series of biaryl products has been prepared starting from aryl bromides and some activated chlorides. The possibility that this catalytic activity might be due to the formation of palladium N‐heterocyclic carbenes has been addressed through solid state ¹³C NMR and the synthesis of an imidazolium analogue in which the acidic 2‐H was replaced with a methyl group.     

Oxime‐Derived Palladium Complexes as Very Efficient Catalysts for the Heck–Mizoroki Reaction

Oxime‐derived, chloro‐bridged palladacycles 16 are efficient complexes for the Heck vinylation of aryl halides. The isolated catalysts are thermally stable, not sensitive to air or moisture and easily accessible from inexpensive starting materials. The reaction can be performed under aerobic conditions, with aryl iodides, bromides and chlorides with acrylic esters and olefins displaying turnover numbers (TON) of up to 10¹⁰ for phenyl iodide and turnover frequencies (TOF) of 1.4×10⁸ h⁻¹. Deactivated aryl bromides undergo the Heck reaction with styrene with TON and TOF values up to 97,000 and 6063 h⁻¹, respectively. Even aryl chlorides undergo the coupling reaction with olefins with TON up to 920. Complexes 16 catalyze the synthesis of 2,3‐disubstituted indenones and indoles in good yields via annulation reaction of internal alkynes with o‐bromo‐ or o‐chlorobenzaldehyde and o‐iodoaniline, respectively.     

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].     

Scope and Limitations of Palladium‐Catalyzed Cross‐Coupling Reactions with Organogold Compounds

Five different alkenylgold(I) phosphane complexes were prepared and then investigated in [1,1′‐bis(diphenylphosphino)ferrocene]palladium(II) dichloride‐catalyzed cross‐coupling reactions with different aryl halides, heterocyclic halides, an alkenyl halide, an alkynyl halide, allylic substrates, benzyl bromide and an acid chloride. With regard to the halides, the iodides were highly reactive, bromides or chlorides gave significantly reduced yields or failed, allylic acetates failed, too. The cross‐coupling partners contained a number of different functional groups, while free carboxylic acids did not deliver cross‐coupling products and o,o‐disubstituted arenes failed as well, a broad range of other functional groups like nitro groups, nitrile groups, ester groups, α,β‐unsaturated ester groups and lactones, aldehydes, alkoxy groups, pyridyl groups, thienyl groups, unprotected phenols and anilines, even aryl azides were tolerated. The structures of one alkenylgold(I) species and of four of the cross‐coupling products were proved by crystal structure analyses.