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.     

Suzuki Coupling Reactions in Pure Water Catalyzed by Supported Palladium – Relevance of the Surface Polarity of the Support

Heterogeneous (supported) palladium catalysts like palladium on carbon and a variety of metal oxides have been shown to be highly active for Suzuki coupling reactions in neat water under mild reaction conditions (T=65 °C). It has been demonstrated for the first time that hydrophobic effects of the catalyst surface play an important role for the catalyst activity in water. Catalysts possessing hydrophobic surfaces (e.g., palladium on carbon) show higher activity for Suzuki coupling reactions in water than their hydrophilic counterparts (palladium on metal oxides). Tuning of the surface polarity of metal oxide supports (by silylation) results in higher activity under these conditions. Stronger alkaline conditions (three‐fold excess of base) compensate the effect of hydrophobic supports and result in high activity of the catalysts also with hydrophilic supports. The addition of tetrabutylammonium bromide to generate, activate and stabilize the catalytic species (dissolved palladium complexes) is necessary for the conversion of more demanding substrates. The reaction is considered to be homogeneous taking place near the catalyst surface inside a droplet or layer of the reactant.     

Solid‐Supported Rhodium(0) Nano‐/Microparticles: An Efficient Ligand‐Free Heterogeneous Catalyst for Microwave‐Assisted Suzuki–Miyaura Cross‐Coupling Reaction

Solid‐supported nano‐ and microparticles of rhodium(0) (SS‐Rh) were prepared and applied as a ligand free heterogeneous catalyst for Suzuki–Miyaura cross‐coupling reaction with wide range of substrate scope. A hitherto unknown Rh‐catalyzed Suzuki cross‐coupling reaction of aldehyde and cyanohaloarenes was observed rather than the usual nucleophilic arylation.The catalyst can be removed by simple filtration and recycled upto twelve runs without any deterioration of activity.     

“Click” Polymer‐Supported Palladium Nanoparticles as Highly Efficient Catalysts for Olefin Hydrogenation and Suzuki Coupling Reactions under Ambient Conditions

Complexation of palladium(II) acetate [Pd(OAc)₂] or dipotassium tetrachloropalladate [K₂PdCl₄] to “click” polymers functionalized with phenyl, ferrocenyl and sodium sulfonate groups gave polymeric palladium(II)‐triazolyl complexes that were reduced to “click” polymer‐stabilized palladium nanoparticles (PdNPs). Transmission electron microscopy (TEM) showed that reduction using sodium borohydride (NaBH₄) produced PdNPs in the 1–3 nm range of diameters depending on the nature of the functional group, whereas slow reduction using methanol yielded PdNPs in the 22–25 nm range. The most active of these PdNPs (0.01% mol Pd), stabilized by poly(ferrocenyltriazolylmethyl)styrene, catalyzed the hydrogenation of styrene at 25 °C and 1 atm hydrogen, with turnover numbers (TONs) of 200,000. When stabilized by the water‐soluble poly(sodium sulfonate‐triazolylmethyl)styrene, the PdNPs (0.01% mol Pd) catalyze the Suzuki–Miyaura coupling between iodobenzene (PhI) and phenylboronic acid [PhB(OH)₂] in water/ethanol (H₂O/EtOH) at 25 °C with TONs of 8,200. This high catalytic activity is comparable to that obtained with “click” dendrimer‐stabilized PdNPs under ambient conditions.     

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.     

Properties and Catalytic Activities of New Easily‐Made Amphiphilic Phosphanes for Aqueous Organometallic Catalysis

Mono‐ and disulfonated amphiphilic versions of triphenylphosphane (PPh₃) and cyclohexyl(phenyl)phosphane were easily synthesized from commercial reagents and sulfuric acid. The behaviour of these phosphanes in solution was investigated by surface tension, isothermal titration calorimetry, nuclear magnetic resonance and cryo‐transmission electron microscopy. Two different supramolecular assemblies were evidenced according to the degree of sulfonation. The monosulfonated phosphanes formed well organized micelle‐like aggregates while the disulfonated phosphanes formed heterogeneous and disorganized vesicle‐like assemblies. The efficiency of these amphiphilic phosphanes was evaluated in the aqueous biphasic, palladium‐catalyzed cleavage of allyl alkyl carbonates.     

New Palladium‐Catalyzed Cascades: 4‐exo‐dig Cyclocarbopalladation Reaction Followed by Suzuki–Miyaura or Sonogashira Cross‐Coupling

Herein we describe new accesses to dienynes and trienynes using new cascade reactions: 4‐exo‐dig cyclocarbopalladation followed by a Suzuki–Miyaura or Sonogashira cross‐coupling.     

Oxime Palladacycle‐Catalyzed Suzuki–Miyaura Alkenylation of Aryl,Heteroaryl, Benzyl,and Allyl Chlorides under Microwave Irradiation Conditions

A simple new protocol for the palladium‐catalyzed Suzuki–Miyaura cross‐coupling of organic chlorides under microwave irradiation is presented. Deactivated aryl and heteroaryl chlorides are efficiently cross‐coupled with alkenylboronic acids and potassium alkenyltrifluoroborates using the 4,4′‐dichlorobenzophenone oxime‐derived palladacycle 1b as precatalyst in 0.1 to 0.5 mol% palladium loading, tris(tert‐butyl)phosphonium tetrafluoroborate {[HP(t‐Bu)₃]BF₄} as ligand, tetra‐n‐butylammonium hydroxide as cocatalyst, and potassium carbonate as base in N,N‐dimethylformamide at 130 °C under microwave irradiation conditions. Under these conditions, styrenes, stilbenes, and alkenylarenes are obtained in good to high yields, and with high regio‐ and diastereoselectivities in only 20 min. The reported protocol is also very efficient for the regioselective alkenylation of benzyl and allyl chlorides to afford allylarenes and 1,4‐dienes.     

3,5‐Bis(n‐perfluorooctyl)benzyltriethylammonium Bromide (F‐TEBA): An Efficient,Easily Recoverable Fluorous Catalyst for Solid‐Liquid PTC Reactions

A readily available 3,5‐bis(perfluorooctyl)benzyl bromide and triethylamine were reacted under mild conditions to give 3,5‐bis(n‐perfluorooctyl)benzyltriethylammonium bromide ( F‐TEBA ), an analogue of the versatile phase‐transfer catalyst, benzyltriethylammonium chloride (TEBA), containing two fluorous ponytails. This perfluoroalkylated quaternary ammonium salt was successfully employed as a catalyst in a variety of reactions run under solid‐liquid phase‐transfer catalysis (SL‐PTC) conditions. Thus, being both hydrophobic and lipophobic, F‐TEBA could be quickly recovered in quantitative yields, and reused without loss of activity over several reaction cycles.     

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.     

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.     

Environmentally Friendly Chemistry Using Supported Reagent Catalysts: Chemically-Modified Mesoporous Solid Catalysts

Chemically-modified mesoporous materials can be prepared as robust catalysts suitable for application in liquid phase processes such as Friedel–Crafts reactions, selective oxidations, nucleophilic substitutions and aromatic brominations. © 1997 SCI.     

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.     

Reusable,Highly Active Heterogeneous Palladium Catalyst by Convenient Self‐Encapsulation Cross‐Linking Polymerization for Multiple Carbon?Carbon Cross‐Coupling Reactions at ppm to ppb Palladium Loadings

Designing reusable high‐performance heterogeneous palladium (Pd) catalysts via convenient, economic synthesis is of great importance to the industrial applications of various carbon‐carbon cross‐coupling reactions. We demonstrate herein a convenient one‐pot self‐encapsulation synthesis of a heterogeneous Pd catalyst [Pd@PDEB, PDEB=poly(1,3‐diethynylbenzene)] directly from commercially available, economic precursors. In the synthesis, the formation of the cross‐linked polymer networks and Pd encapsulation are accomplished simultaneously, turning a homogeneous Pd polymerization catalyst into the heterogeneous cross‐coupling catalyst. As a unique, practical heterogeneous catalyst, Pd@PDEB shows remarkably high activity, high reusability, and high versatility towards at least four types of cross‐coupling reactions (Suzuki–Miyaura, Stille, allylic arylation, and Mizoroki–Heck reactions) with even difficult reactants (aryl chlorides and heteroaryl halides) under aerobic conditions with Pd loadings down to ppm or even ppb levels. Evidences from hot filtration and 3‐phase tests demonstrate the heterogeneous nature of the catalyst with very low Pd leaching and negligible contributions of leached homogeneous Pd species towards the coupling reactions.

     

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.     

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.     

Asymmetric Carbon‐Carbon Bond Forming Reactions Catalysed by Metal(II) Bis(oxazoline) Complexes Immobilized using Supported Ionic Liquids

A series of bis(oxazoline) metal(II) complexes has been supported on silica and carbon supports by non‐covalent immobilisation using an ionic liquid. The catalytic performance of these solids was compared for the enantioselective Diels–Alder reaction between N‐acryloyloxazolidinone and cyclopentadiene and the Mukaiyama‐aldol reaction between methyl pyruvate and 1‐methoxy‐1‐trimethylsilyloxypropene. In both reactions the enantioselectivity was strongly influenced by the choice of support displaying enantioselectivies (ee values) up to 40% higher than those conducted under homogeneous reaction conditions.     

Suzuki–Miyaura Cross‐Coupling of 2‐Nitroarenediazonium Tetrafluoroborates: Synthesis of Unsymmetrical 2‐Nitrobiphenyls and Highly Functionalized Carbazoles

The Suzuki–Miyaura cross‐coupling of 2‐nitrodiazonium tetrafluoroborate salts with substituted boronic acids is an effective and efficient means of preparing highly functionalized 2‐nitrobiphenyls in modest to excellent yield under extremely mild reaction conditions. Cross‐coupling of 2‐nitrodiazonium tetrafluoroborate salts with ortho‐methoxy‐ and benzyloxyphenylboronic acids was also demonstrated leading to the ortho‐ortho‐2‐nitrobiphenyls. Reductive cyclization of the 2‐nitrobiphenyl products allows for the overall three‐step synthesis of uniquely substituted carbazoles from readily available 2‐nitroanilines. The methodology was further highlighted by the short total synthesis of the carbazole alkaloids clausine V, N, C, and glycoborine.