Convenient Approach to 3,4‐Diarylisoxazoles Based on the Suzuki Cross‐Coupling Reaction

The Suzuki cross‐coupling reaction was found effective for rapid access to a series of 3,4‐diarylisoxazoles of pharmacological interest. The efficiency of this approach was demonstrated by the synthesis of the highly potent COX‐2‐selective inhibitor, 4‐(5‐methyl‐3‐phenyl‐4‐isoxazolyl)benzenesulfonamide (valdecoxib), and its analogues. Thus, the coupling reaction between (3‐aryl‐5‐methyl‐4‐isoxazolyl)boronic acids, prepared in situ from the corresponding bromides using triisopropyl borate, and aryl bromides containing a 4‐sulfonamide or 4‐methylsulfonyl group under the standard conditions [Pd(PPh₃)₄, Na₂CO₃, EtOH‐H₂O, reflux] yielded the target 3,4‐diarylisoxazoles in good yields.     

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.     

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‐Catalysed Regioselective Sequential C‐5 and C‐2 Direct Arylations of 3‐Acetylpyrroles with Aryl Bromides

The PdCl(C₃H₅)(dppb)/KOAc system was found to be effective for the direct regioselective C‐5 arylation of 3‐acetylpyrroles with ortho‐substituted aryl bromides. This procedure has been found to be tolerant to a variety of functional groups at C‐2 of the aryl bromide such as methyl, formyl, nitrile, nitro, hydroxymethyl, chloro, fluoro or trifluoromethyl. The sequential direct C‐5 arylation followed by C‐2 arylation of such 3‐substituted pyrroles allows the synthesis of 2,5‐diaryl‐3‐acetylpyrroles in high yields.     

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.     

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.     

Fluorapatite‐Supported Palladium Catalyst for Suzuki and Heck Coupling Reactions of Haloarenes

A fluorapatite‐supported palladium catalyst (PdFAP) was synthesized by treatment of fluorapatite (prepared by incorporating the basic species fluoride ion into apatite in situ by co‐precipitation) with bis(benzonitrile)palladium(II ) chloride in acetone. The catalyst displayed high catalytic activity for Suzuki coupling of aryl iodides and bromides with boronic acids at room temperature and chloroarenes at 130 °C in the presence of tetrabutylammonium bromide to give biaryls in excellent yields. Heck olefination of chloroarenes was also successfully carried out by this catalyst. PdFAP was recovered quantitatively by simple filtration and reused with consistent activity. PdFAP was well characterized by XRD, FTIR, XPS, ICP‐AES, CO₂ TPD and CHN elemental analysis.     

Efficient Synthesis of Substituted Selenophenes Based on the First Palladium(0)‐Catalyzed Cross‐Coupling Reactions of Tetrabromoselenophene

Regioselective Suzuki cross‐coupling reactions of tetrabromoselenophene allow a convenient synthesis of aryl‐substituted selenophenes. High yields were obtained using a novel biaryl‐monophosphine ligand. The first tetra(1‐alkynyl)selenophene was prepared in one step by a Sonogashira reaction of tetrabromoselenophene.     

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.     

Reversed‐Polarity Synthesis of Diaryl Ketones through Palladium‐Catalyzed Direct Arylation of 2‐Aryl‐1,3‐dithianes

An umpolung approach to the synthesis of diaryl ketones has been developed based on in situ generation of acyl anion equivalents and their catalytic arylation. This method entails the base‐promoted, palladium‐catalyzed direct C‐H arylation of 2‐aryl‐1,3‐dithianes with aryl bromides. Use of MN(SiMe₃)₂ (M=Li, Na) base results in reversible deprotonation of the weakly acidic dithiane. In the presence of a Pd(NiXantphos)‐based catalyst and aryl bromide, cross‐coupling of the metallated 2‐aryl‐1,3‐dithiane takes place under mild conditions (2 h at rt) with yields as high as 96 %. The resulting 2,2‐diaryl‐1,3‐dithianes were converted into diaryl ketones by either molecular iodine, N‐bromo succinimide (NBS) or Selectfluor in the presence of water. The dithiane arylation/hydrolysis can be performed in a one‐pot procedure to yield a variety of diaryl ketones in good to excellent yields. This method is suitable for rapid and large‐scale synthesis of diaryl ketones. A one‐pot preparation of anti‐cholesterol drug fenofibrate (TriCor®) has been achieved on 10.0 mmol scale in 86 % yield.

     

Diethanol amine‐functionalized polymer‐supported palladium (0) complex as catalyst for Suzuki cross‐coupling reaction in water

Diethanol amine‐functionalized polymer‐supported palladium (0) complex as catalyst for Suzuki cross‐coupling reaction in water was synthesized and characterized. The catalyst exhibits excellent catalytic activity and stability in the Suzuki cross‐coupling reaction. Various aryl bromides were coupled with aryl boronic acids in water, under air, and in the presence of 0.5 mol % of the catalyst to afford corresponding cross‐coupled products in high yields at 100°C. Furthermore, the heterogeneous catalyst can be readily recovered by simple filtration and reused for several times only with a slight decrease in its activity. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

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.     

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.     

Palladium‐Catalyzed Aryl Amination Reactions of 6‐Bromo‐ and 6‐Chloropurine Nucleosides

Palladium‐catalyzed C N bond forming reactions of 6‐bromo‐ as well as 6‐chloropurine ribonucleosides and the 2′‐deoxy analogues with arylamines are described. Efficient conversions were observed with palladium(II) acetate/Xantphos/cesium carbonate, in toluene at 100 °C. Reactions of the bromonucleoside derivatives could be conducted at a lowered catalytic loading [5 mol% Pd(OAc)₂/7.5 mol% Xantphos], whereas good product yields were obtained with a higher catalyst load [10 mol% Pd(OAc)₂/15 mol% Xantphos] when the chloro analogue was employed. Among the examples evaluated, silyl protection for the hydroxy groups appears better as compared to acetyl. The methodology has been evaluated via reactions with a variety of arylamines and by synthesis of biologically relevant deoxyadenosine and adenosine dimers. This is the first detailed analysis of aryl amination reactions of 6‐chloropurine nucleosides, and comparison of the two halogenated nucleoside substrates.     

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.     

Palladium‐Iminodiacetic Acid Immobilized on pH‐Responsive Polymeric Microspheres: Efficient Quasi‐Homogeneous Catalyst for Suzuki and Heck Reactions in Aqueous Solution

The pH‐responsive core‐shell microspheres of poly(styrene‐co‐methylacrylic acid) (PS‐co‐PMAA) containing a polystyrene (PS) core and a poly(methylacrylic acid) (PMAA) shell are synthesized by one‐stage soap‐free copolymerization and the catalyst system palladium‐iminodiacetic acid (IDA‐Pd) is immobilized on the outer shell‐layer of the core‐shell microspheres to form the quasi‐homogeneous and easily accessible catalyst PS‐co‐PMAA‐IDA‐Pd. This quasi‐homogeneous PS‐co‐PMAA‐IDA‐Pd catalyst is highly dispersed in the reaction medium just like a homogeneous one and can be separated like a heterogeneous catalyst by adjusting the pH of the reaction medium. Suzuki reactions employing the quasi‐homogeneous PS‐co‐PMAA‐IDA‐Pd catalyst are efficiently performed in water as the sole solvent under mild conditions such as room temperature. The PS‐co‐PMAA‐IDA‐Pd catalyst is also used in Heck reactions of a wide range of aryl halides with styrene and proves to be efficient in aqueous solution. The PS‐co‐PMAA‐IDA‐Pd catalyst has a low leaching loss and can be reused at least 4 times without loss of activity.     

Synthesis of 3,4‐Disubstituted Quinolin‐2‐(1H)‐ones via Palladium‐Catalyzed Decarboxylative Arylation Reactions

The Pd‐catalyzed decarboxylative cross‐coupling reaction of 4‐substituted quinolin‐2(1H)‐one‐3‐carboxylic acids with (hetero)aryl halides is described. With palladium(II) bromide and triphenylarsine ligand as the catalyst system, a variety of 4‐substituted 3‐(hetero)aryl quinolin‐2(1 H)‐ones and related heterocycles, such as 4‐substituted 3‐arylcoumarins can be prepared in good to excellent yields.     

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.     

Synthesis of 2,4‐ and 2,5‐Disubstituted Oxazoles via Metal‐ Catalyzed Cross‐Coupling Reactions

The rapid synthesis of 2,4‐ and 2,5‐disubstituted oxazoles via metal‐catalyzed cross‐coupling reactions is reported. The 4‐ or 5‐position of the corresponding 4‐ or 5‐halogenated 2‐butylthiooxazoles was successfully functionalized via Suzuki–Miyaura, Sonogashira and Stille cross‐coupling reactions. The 2‐position of the 2‐butylthiooxazoles obtained was further coupled to various organozinc reagents through palladium‐ or nickel‐mediated cross‐coupling reactions.     

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.