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.     

The Clicked Pyridyl‐Triazole Ligand: From Homogeneous to Robust,Recyclable Heterogeneous Mono‐ and Polymetallic Palladium Catalysts for Efficient Suzuki–Miyaura,Sonogashira, and Heck Reactions

Various mono‐ and polymetallic palladium complexes containing a 2‐pyridyl‐1,2,3‐triazole (pyta) ligand or a nonabranch‐derived (nonapyta) ligand have been synthesized by reaction of palladium acetate with these ligands according to a 1:1 metal‐ligand stoichiometry and used as catalysts for carbon‐carbon cross‐coupling including the Suzuki–Miyaura, Sonogashira and Heck reactions. The unsubstituted monopalladium and nonapalladium complexes were insoluble in all the reaction media, whereas tri‐ and tetranuclar palladium complexes were soluble, which allowed conducting catalysis under either homogeneous or heterogeneous conditions. The organopalladium complexes were characterized by standard analytical and spectroscopic methods and by thermogravimetry showing decomposition above 110 °C. Both types of catalysts showed excellent activity for these cross carbon‐carbon bond formations involving aryl halides including activated aryl chlorides or acyl chloride. Besides the comparison between homogeneous and heterogeneous catalysis, the key feature of these catalysts is their remarkable robustness that allowed recycling at least ten times in the example of the Heck reaction with excellent yields and without significant reduction of the conversion.     

Highly Active,Well‐Defined (Cyclopentadiene)(N‐heterocyclic carbene)palladium Chloride Complexes for Room‐Temperature Suzuki–Miyaura and Buchwald–Hartwig Cross‐Coupling Reactions of Aryl Chlorides and Deboronation Homocoupling of Arylboronic Acids

A new class of well‐defined N‐heterocyclic carbene (NHC)‐(cyclopentadiene)palladium chloride complexes such as CpPd(NHC)Cl wasw synthesized from the readily available starting NHC‐palladium(II) chloride dimers. These air‐stable, coordinatively saturated NHC‐Pd complexes bearing the cyclopentadiene (Cp) unit exhibit high catalytic activity in the room temperature Suzuki–Miyaura and Buchwald–Hartwig cross‐coupling reactions involving unactive aryl chlorides as the substrates. In addition, they are found to be extremely efficient catalysts in the deboronation homocoupling of arylboronic acids at room temperature.     

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.     

Thiosemicarbazone Salicylaldiminato‐Palladium(II)‐Catalyzed Mizoroki–Heck Reactions

Four tridentate thiosemicarbazone salicylaldiminato‐palladium(II) complexes of the general formula [Pd(saltsc‐R)PPh₃] [saltsc=salicylaldehyde thiosemicarbazone; R=H ( 1 ), 3‐tert‐butyl ( 2 ), 3‐methoxy ( 3 ), 5‐chloro ( 4 )], have been evaluated as catalyst precursors for the Mizoroki–Heck coupling reaction between a variety of electron‐rich and electron‐poor aryl halides and olefins. The palladium complexes (0.1–1 mol% loading) were found to effectively catalyze these reactions with high yields being obtained when aryl iodides and aryl bromides were utilized. The effects of base, catalyst loading, reaction temperature and reaction time on the catalytic activity of the most active complex were also investigated.     

Palladium‐Catalyzed Direct Arylations of 1,2,3‐Triazoles with Aryl Chlorides using Conventional Heating

Generally applicable, palladium‐catalyzed direct arylations of 1,2,3‐triazoles with aryl chlorides were accomplished through conventional heating at reaction temperatures of 105–120 °C. Thereby, intra‐ and intermolecular C H bond functionalizations were achieved with a variety of differently substituted chlorides as electrophiles, bearing numerous valuable functional groups.     

Recoverable Palladium Catalysts for Suzuki–Miyaura Cross‐ Coupling Reactions Based on Organic‐Inorganic Hybrid Silica Materials Containing Imidazolium and Dihydroimidazolium Salts

The systems formed by palladium acetate [Pd(OAc)₂] and hybrid silica materials prepared by sol‐gel from monosilylated imidazolium and disilylated dihydroimidazolium salts show catalytic activity in Suzuki–Miyaura cross‐couplings with challenging aryl bromides and chlorides. They are very efficient as recoverable catalysts with aryl bromides. Recycling is also possible with aryl chlorides, although with lower conversions. In situ formation of palladium nanoparticles has been observed in recycling experiments.     

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.     

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.     

Fast Suzuki–Miyaura Cross‐Coupling Reaction with Hexacationic Triarylphosphine Bn‐Dendriphos as Ligand

The application of hexa[(dimethylamino)methyl]‐functionalized triphenylphosphine ( 1 ) and its benzylammonium salt, Bn‐Dendriphos ( 2 ), in the Suzuki–Miyaura cross‐coupling of aryl bromides with arylboronic acids is described. The 3,5‐bis[(benzyldimethylammonio)methyl] substitution pattern in 2 leads to a rate enhancement compared to both the non‐ionic parent compound 1 and triphenylphospine (PPh₃) itself. At the same time, the resulting catalytic species are stable towards palladium black formation, even at a phosphine/palladium ratio of 1. These observations are attributed to the presence of a total of six ammonium groups in the backbone of the phosphine ligand, which presumably leads to an unsaturated phosphine‐palladium complex.     

Macrocyclic Palladium(II) Complexes in C?C Coupling Reactions: Efficient Catalysis by Controlled Temporary Release of Active Species

Stabilization of palladium species against agglomeration is essential for reasonable catalytic activity in C C coupling reactions. In contrast to common methods of palladium(0) complex or particle stabilization, a new concept is introduced here: it is demonstrated that a controlled release of palladium from an inactive precatalyst provides stability, too, and leads to high catalytic activity. This paper presents surprising catalytic results for Heck and Suzuki reactions with aryl chlorides and bromides, using three highly stable macrocyclic palladium complexes as catalyst precursors. Three different behaviour patterns for the macrocyclic complexes can be deduced from the evaluation of catalytic activities, UV‐Vis spectroscopy, recycling studies of immobilized complexes, and ligand addition experiments. (i) Palladium tetraphenylporphyrin reversibly releases only extremely low amounts of palladium during the reactions, and low coupling activities are observed. (ii) Release of palladium from its phthalocyanine complex is irreversible; cumulative release of palladium into the reaction mixtures leads to high catalytic activity. (iii) Extraordinary results were obtained with a Robson‐type complex of palladium, which reversibly releases effectual amounts of palladium into solution under reaction conditions. This controlled release prevents the formation of inactive palladium agglomerates under harsh conditions and leads to high catalytic performances. Even strongly deactivated electron‐rich aryl chlorides (4‐chloroanisole) can be completely and selectively converted by the in situ formed anionic palladium halide complexes; the addition of typical stabilizing additives (TBAB) was found to be unnecessary. The bimetallic palladium complex is regenerated at the end of the reaction. These results contribute to the current understanding of the active species in C C coupling reactions of Heck and Suzuki types.     

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.     

Amine–Borane Complexes: Air‐ and Moisture‐Stable Partners for Palladium‐Catalyzed Borylation of Aryl Bromides and Chlorides

A method for using amine–borane complexes directly in palladium catalyzed borylation has been developed. The reaction proceeds through the sequential formation of a boronium species followed by deprotonation leading to the aminoborane. This reagent is then directly used in the borylation process leading, after work‐up, to various boronic acid derivatives. The reaction was applied to (hetero)aryl triflates, iodides, bromides and chlorides.

     

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.     

Zheda‐Phos for General α‐Monoarylation of Acetone with Aryl Chlorides

A new, readily available, and air‐stable monophosphine ligand, i.e., Zheda‐Phos , has been developed for the general and highly effective palladium‐catalyzed monoarylation of acetone with aryl chlorides. The reaction rate is of first‐order dependence with the aryl chloride.     

Supported Palladium Catalysts for Suzuki Reactions: Structure‐Property Relationships,Optimized Reaction Protocol and Control of Palladium Leaching

Palladium on metal oxides and on activated carbon with particular properties (high palladium dispersion, low degree of reduction, water content) are shown to be highly active (tunrover number, TON=20,000; turnover frequency, TOF=16,600), selective and robust catalysts for Suzuki cross‐couplings of aryl bromides and activated aryl chlorides. Catalysts and reaction protocol offer combined advantages of high catalytic efficiency under ambient conditions (air and moisture), easy separation and reuse and quantitative recovery of palladium. The palladium concentration in solution during the reaction correlates clearly with the progress of the reaction and indicates that dissolved molecular palladium is in fact the catalytically active species. Dissolved palladium is redeposited onto the support at the end of the reaction. Additional minimization of the palladium content in solution (down to 0.1 ppm) could be achieved by simple procedures which meet the requirements of pharmaceutical industry.     

Expanded Heterogeneous Suzuki–Miyaura Coupling Reactions of Aryl and Heteroaryl Chlorides under Mild Conditions

A mesoporous LTA zeolite (MP‐LTA)‐supported palladium catalyst was developed for the highly efficient Suzuki–Miyaura reaction of aryl and heteroaryl chlorides. The couplings of various aryl chlorides with arylboronic acids in aqueous ethanol were efficiently achieved in the presence of 1.0 mol% of the catalyst. Furthermore, the scope of this catalyst was extended to the coupling of heteroaryl chlorides. Regardless of the substituents, all of the coupling reactions were very clean and highly efficient under mild heating. It shows that our catalyst is one of the most powerful heterogeneous catalysts for the coupling of a wide range of aryl and heteroaryl chlorides. The catalyst could be repetitively used at least 10 times without a significant loss of its catalytic activity. Compared to mesoporous SBA‐15 and MCM‐41 materials, the MP‐LTA support proved to be very stable and robust to prevent degradation upon reuse.     

Insights into the Role of New Palladium Pincer Complexes as Robust and Recyclable Precatalysts for Suzuki–Miyaura Couplings in Neat Water

Suzuki–Miyaura biaryl and diarylmethane syntheses via the coupling of arylboronic acids with aryl and arylmethyl bromides are performed in water by means of two new CNC‐type palladium pincer complexes. Good to excellent results (including high TON values and extended recycling procedures) are obtained in most cases for a range of electronically dissimilar halides and boronic acids. On the basis of a series of kinetics studies, transmission electron microscopy (TEM), mercury drop tests, and quantitative poisoning experiments, the real role of the latter palladacycles, closely linked to the formation and active participation of palladium nanoparticles, is discussed.     

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.     

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].