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.     

Suzuki–Miyaura Cross‐Coupling With Quasi‐Heterogeneous Palladium

The Suzuki–Miyaura cross‐coupling reaction using heterogeneous Pd/C has a homogeneous component. The soluble palladium concentration increases during the reaction reaching a maximum at ca. 90% conversion before falling to <4 ppm.     

Aryl Diazonium versus Iodonium Salts: Preparation,Applications and Mechanisms for the Suzuki–Miyaura Cross‐Coupling Reaction

This review gives an overview of the use of unusual diazonium and iodonium salts as electrophiles for the Suzuki–Miyaura reaction. The discussion mainly focuses, with a critical view, on catalytic systems developed with these electrophiles. The review also discusses their general properties and preparation as well as mechanistic aspects. A last and brief comparison of diazonium versus iodonium salts, by highlighting advantages and drawbacks of both, gives the reader an understandable resumé.     

Selective Palladium‐Catalyzed Suzuki–Miyaura Reactions of Polyhalogenated Heteroarenes

The palladium‐catalyzed Suzuki–Miyaura reaction of multiply halogenated, electron‐rich and electron‐deficient heteroarenes is one of the most reliable and environmentally friendly tools for installing a wide range of non‐functionalized and functionalized carbon substituents onto heteroaromatic systems with exquisite chemo‐ and site‐selectivity. For substrates with different halogen groups the chemoselectivity of the Suzuki–Miyaura reactions has been found to be dependent on the reactivity difference between the halogens. However, the hardest achievement of selectivity in Suzuki–Miyaura monocouplings involving polyhalogenated heteroarenes with identical halogen atoms has been shown to be dominated by steric and electronic effects and the presence of directing groups at positions neighbouring the reaction sites. Moreover, in the case of symmetrically substituted dihaloheteroarenes with identical halogen atoms, highly selective monocoupling reactions have often been achieved only after a careful optimization of reaction parameters including the catalyst precursor, base, solvent, and the molar ratio between electrophile and organoboron reagent. This critical review with 341 references covers developments on the chemo‐ and site‐selective Suzuki–Miyaura monocoupling reactions of polyhalogenated heteroarenes with different or identical halogen atoms. It also includes the synthesis of polysubstituted heteroarenes, not easily accessible by other means, via consecutive monocoupling reactions and/or a more synthetically valuable approach involving one‐pot polycoupling reactions.     

The Actual Active Species of Sulfur‐Modified Gold‐Supported Palladium as a Highly Effective Palladium Reservoir in the Suzuki–Miyaura Coupling

The actual active species of the recently developed sulfur‐modified, gold‐supported palladium material, S ‐modified A u‐supported Pd (SAPd), with one of the lowest Pd‐releasing levels and high recyclability in the Suzuki–Miyaura coupling, was investigated. Also, SAPd was found to work repeatedly as an excellent Pd reservoir for liquid‐phase combinatorial synthesis.     

Cross‐Coupling in Flow using Supported Catalysts: Mild,Clean, Efficient and Sustainable Suzuki–Miyaura Coupling in a Single Pass

A mild, clean, practical, sustainable and high yielding procedure for Suzuki–Miyaura cross‐coupling in a single pass using a silica‐supported palladium catalyst is described. The catalyst can be used in more than 30 reactions and for more than 8 h of continuous processing without a decrease in reactivity due to the low leaching observed. Different halides/pseudo‐halides and organoboron compounds can be used without modifying the standard procedure.     

Nickel‐Catalyzed Suzuki–Miyaura Coupling of a Tertiary Iodocyclopropane with Wide Boronic Acid Substrate Scope: Coupling Reaction Outcome Depends on Radical Species Stability

We describe a nickel‐catalyzed Suzuki–Miyaura arylation of a tertiary iodocyclopropane with arylboronic acids; this is an efficient and convergent strategy for providing various enantioenriched arylcyclopropanes with a quaternary stereogenic center. This is the first metal‐catalyzed coupling between a tertiary alkyl electrophile and a wide range of aromatics, including heteroaromatics. We found that the outcome of the Ni‐catalyzed coupling with halides as electrophiles was dependent on the stability of the radical species formed during the reaction. The use of tert‐butyl alcohol (t‐BuOH) as the reaction solvent was very effective, because of its stability under the radical‐generating reaction conditions.

     

Aerobic Ligand‐Free Suzuki Coupling Reaction of Aryl Chlorides Catalyzed by In Situ Generated Palladium Nanoparticles at Room Temperature

An aerobic, ligand‐free Suzuki coupling reaction catalyzed by in situ generated palladium nanoparticles in polyethylene glycol with an average molecular weight of 400 Da (PEG‐400) at room temperature has been developed. This catalytic system is a very simple and highly active protocol for the Suzuki coupling of aryl chlorides with arylboronic acids, which proceed smoothly in excellent yields in short times using low catalyst loadings. Control experiments demonstrated that the Suzuki reaction catalyzed by the in situ generated palladium nanoparticles can be carried out much quicker than that using the preprepared particles under the same conditions. The formation of palladium nanoparticles in PEG‐400 was promoted by arylboronic acids.     

Palladium Supported on Cross‐Linked Imidazolium Network on Silica as Highly Sustainable Catalysts for the Suzuki Reaction under Flow Conditions

Highly cross‐linked imidazolium‐based materials, obtained by radical oligomerization of bis‐vinylimidazolium salts in the presence of 3‐mercaptopropyl‐modified silica gel, were used as supports for palladium catalysts. Thanks to the high imidazolium loading these materials were able to support a high amount of the metal (10 wt%). Such materials were characterized by several techniques (¹³C magic angle spinning nuclear magnetic resonance, the Brunauer–Emmett–Teller technique, X‐ray photoelectron spectroscopy, and transmission electron microscopy). The palladium catalysts displayed good activity allowing the synthesis of several biphenyl compounds in high yields working with only 0.1 mol% of palladium loading at 50 °C in ethanol/water under batch condition. Moreover, a flow apparatus, to optimize the efficiency of the isolation of the pure products and minimize waste (E‐factor), was investigated. For the first time the palladium catalyst and base (K₂CO₃) were placed in two separate columns allowing an easy recovery of the products with very low E‐factor values (<4). Waste production was reduced by over 99% compared to classic batch conditions. Because of the high Pd loading only 42 mg of catalysts were employed in the Suzuki reaction between 160 mmol of 4‐bromotoluene and 180 mmol of phenylboronic acid. No loss in activity was observed.     

The 1,3‐Diaminobenzene‐Derived Aminophosphine Palladium Pincer Complex {C6H3[NHP(piperidinyl)2]2Pd(Cl)} – A Highly Active Suzuki–Miyaura Catalyst with Excellent Functional Group Tolerance

The rapidly prepared 1,3‐diaminobenzene‐derived aminophosphine pincer complex {C₆H₃[NHP(piperidinyl)₂]₂Pd(Cl)} ( 1 ) is an effective Suzuki catalyst with excellent functional group tolerance. Side‐product formations, such as homocoupling, debromation or protodeboration have only rarely been detected and if so, were in all cases below the 5% level. The presented reaction protocol is universally applicable. Experimental observations indicate that palladium nanoparticles are the catalytically active form of 1 .     

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.     

On the Nature of the Active Species in Palladium Catalyzed Mizoroki–Heck and Suzuki–Miyaura Couplings – Homogeneous or Heterogeneous Catalysis,A Critical Review

A wide array of forms of palladium has been utilized as precatalysts for Heck and Suzuki coupling reactions over the last 15 years. Historically, nearly every form of palladium used has been described as the active catalytic species. However, recent research has begun to shed light on the in situ transformations that many palladium precatalysts undergo during and before the catalytic reaction, and there are now many suggestions in the literature that narrow the scope of types of palladium that may be considered true “catalysts” in these coupling reactions. In this work, for each type of precatalyst, the recent literature is summarized and the type(s) of palladium that are proposed to be truly active are enumerated. All forms of palladium, including discrete soluble palladium complexes, solid‐supported metal ligand complexes, supported palladium nano‐ and macroparticles, soluble palladium nanoparticles, soluble ligand‐free palladium, and palladium‐exchanged oxides are considered and reviewed here. A considerable focus is placed on solid precatalysts and on evidence for and against catalysis by solid surfaces vs. soluble species when starting with various precatalysts. The review closes with a critical overview of various control experiments or tests that have been used by authors to assess the homogeneity or heterogeneity of catalyst systems.     

Mechanistic Studies on the Palladium‐Catalyzed Direct C‐5 Arylation of Imidazoles: The Fundamental Role of the Azole as a Ligand for Palladium

An in‐depth mechanistic study on the palladium‐catalyzed direct arylation of imidazoles at the C‐5 position is presented. The interactions of triphenylphosphine (PPh₃)‐ligated aryl‐Pd species with 1,2‐dimethyl‐1H‐imidazole (dmim) have been studied in detail. In contrast with previous suggestions, phosphine‐ligated organo‐Pd species are not active and the reaction proceeds through imidazole‐ligated organo‐Pd intermediates. The kinetics of the oxidative addition of aryl halides with dmim‐ligated Pd(0) species have been characterized in a Pd(dba)₂/dmim model system. A thorough study of the equilibria involving novel [ArPd(dmim)₂X] complexes (X=I, OAc) and the unexpected cationic [ArPd(dmim)₃]⁺ is also reported. The ability of these species to effect the C H arylation of dmim at room temperature in the presence of acetate is also demonstrated.

     

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.     

Iron‐Catalyzed Mizoroki–Heck Cross‐Coupling Reaction with Styrenes

In the presence of iron(II) chloride (FeCl₂; 20 mol%) and potassium tert‐butoxide (t‐BuOK; 4 equiv.) in dimethyl sulfoxide (DMSO), aryl and heteroaryl iodides undergo stereoselective Mizoroki–Heck C C cross‐coupling reactions with styrenes at 60 °C giving the corresponding (E)‐alkenes. The best yields are obtained upon adding a ligand (80 mol%) such as proline or picolinic acid. Aryl bromides and pyridinyl bromides are also coupled with styrenes but in lower yields.     

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.

     

Handy Protocols using Vinyl Nosylates in Suzuki–Miyaura Cross‐Coupling Reactions

Vinyl nosylates derived from 1,3‐dicarbonyl compounds could be engaged in Suzuki–Myaura cross coupling reactions with aryl‐, vinyl‐ and methylboronic acids or trifluoborate derivatives at room temperature in the presence of 2 mol% of [1,1′‐bis(diphenylphosphino)ferrocene]dichloropalladium(II) [PdCl₂(dppf)]. One‐pot procedures have been set up for practical and efficient nosylation–cross‐coupling reactions. Nosylate, as a cheap novel pseudo‐halide, gives very stable compounds and is very efficient in Suzuki–Myaura cross coupling reactions (21 examples, 44–99%).

     

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.     

Iron‐Catalyzed Ligand‐Free Carbon‐Selenium (or Tellurium) Coupling of Arylboronic Acids with Diselenides and Ditellurides

Carbon‐selenium and carbon‐tellurium cross‐couplings of arylboronic acids with diselenides and ditellurides have been catalyzed by iron(0), iron(II) chloride or iron(III) chloride without any ligand and additive in the air. The method yields the corresponding unsymmetrical diorgano monoselenides and monotellurides in good to excellent yields, displays a broad substrate scope, and is simple, convenient, effective, economical and environmentally friendly.