Heck reactions of aryl halides with alk‐1‐en‐3‐ol derivatives catalysed by a tetraphosphine–palladium complex

cis,cis,cis‐1,2,3,4‐Tetrakis(diphenylphosphinomethyl)cyclopentane–[PdCl(C₃H₅)]₂ efficiently catalyses the Heck reaction of alk‐1‐en‐3‐ol with a variety of aryl halides. In the presence of hex‐1‐en‐3‐ol or oct‐1‐en‐3‐ol, the β‐arylated carbonyl compounds were selectively obtained. Turnover numbers up to 84 000 can be obtained for this reaction. Linalool and 2‐methylbut‐3‐en‐2‐ol led regio‐ and stereoselectively to the corresponding (E)‐1‐arylalk‐1‐en‐3‐ol derivatives. A minor electronic effect of the substituents of the aryl bromide was observed. Quite similar reaction rates were generally observed in the presence of activated aryl bromides such as bromoacetophenone and deactivated aryl bromides such as bromoanisole, indicating that, with these alkenols and this catalyst, the oxidative addition of aryl bromides to palladium is not the rate‐limiting step. It should be noted that this reaction also proceeds with sterically very congested aryl bromides such as 9‐bromoanthracene or 2,4,6‐triisopropylbromobenzene or with a vinyl bromide. On the other hand, low yields were obtained with aryl chlorides. Copyright © 2006 John Wiley & Sons, Ltd.     

Sustainable Heck–Matsuda Reaction with Catalytic Amounts of Diazonium Salts: An Experimental and Theoretical Study

The palladium‐catalyzed Heck–Matsuda reaction with a catalytic amount of an in‐situ‐generated diazonium salt proceeded under mild and sustainable conditions. The reaction proceeded at room temperature, under base‐free conditions, and only generated tBuOH, H₂O, and N₂ as by‐products. Ortho‐substituted diazonium salts were more‐efficiently coupled to methyl acrylate than their corresponding para isomers, which required the addition of anisole as an additive. In support of these experimental data, we carried out theoretical studies to gain a deeper understanding of these reaction outcomes.     

Modular One‐Step Three‐Component Synthesis of Tetrahydroisoquinolines Using a Catellani Strategy

Reported is a modular one‐step three‐component synthesis of tetrahydroisoquinolines using a Catellani strategy. This process exploits aziridines as the alkylating reagents, through palladium/norbornene cooperative catalysis, to enable a Catellani/Heck/aza‐Michael addition cascade. This mild, chemoselective, and scalable protocol has broad substrate scope (43 examples, up to 90 % yield). The most striking feature of this protocol is the excellent regioselectivity and diastereoselectivity observed for 2‐alkyl‐ and 2‐aryl‐substituted aziridines to access 1,3‐cis‐substituted and 1,4‐cis‐substituted tetrahydroisoquinolines, respectively. Moreover, this is a versatile process with high step and atom economy.     

Flexible,dicationic imidazolium salts for in situ application in palladium‐catalysed Mizoroki–Heck coupling of acrylates under aerobic conditions

The synthesis, characterization and in situ catalytic performance of new unsymmetric N,N′‐disubstituted imidazolium‐based dicationic salts in Mizoroki–Heck coupling of acrylates with aryl bromides under aerobic conditions are described. A series of flexible dicationic salts with varying steric and electronic properties were synthesized in good to excellent yields. All the salts were well characterized using spectroscopic techniques. X‐ray diffraction analysis of two salts with the same dicationic backbone and different counter anions shows that the ligand adopts two different conformations which are influenced by the nature of the anion. Thus, the ligand is capable of changing its conformation according to the change in environment due to its flexible nature. All the synthesized imidazolium salts were found to be active in in situ palladium‐catalysed Mizoroki–Heck coupling under aerobic conditions. Amongst the salts, the hydroxyl‐functionalized imidazolium salt, incorporating the features of both bidentate chelating O,O ligand and carbene, shows the maximum catalytic activity. A variety of aryl and heteroaryl methyl and ethyl cinnamates were synthesized using these imidazolium salts as preligands. In addition, NMR studies confirm in situ generation of normal N‐heterocyclic carbenes from the C‐2 position of imidazol‐2‐ylidene ring. The mercury poisoning test was also performed to ascertain the nature of catalytically active palladium species. Aerobic conditions, low catalytic loading (0.5 mol%), shorter reaction times, broad functional group tolerance and good to excellent isolated yields are some of the significant features of the novel catalytic systems described here. Copyright © 2016 John Wiley & Sons, Ltd.     

Nitro group reduction and Suzuki reaction catalysed by palladium supported on magnetic nanoparticles modified with carbon quantum dots generated from glycerol and urea

Glycerol and urea were used as green and cheap sources of carbon quantum dots (CQD) for modifying Fe₃O₄ nanoparticles (NPs). The obtained CQD@Fe₃O₄ NPs were used for the stabilization of palladium species and the prepared catalyst, Pd@CQD@Fe₃O₄, was characterized using various techniques. This magnetic supported palladium was applied as an efficient catalyst for the reduction of aromatic nitro compounds to primary amines at room temperature using very low palladium loading (0.008 mol%) and also for the Suzuki–Miyaura cross‐coupling reaction of aryl halides as well as challenging heteroaryl bromides and aryl diazonium salts with arylboronic acids and with potassium phenyltrifluoroborate. This magnetically recyclable catalyst was recovered and reused for seven consecutive runs in the reduction of 4‐nitrotoluene to p‐toluidine and for ten consecutive runs in the reaction of 4‐iodoanisole with phenylboronic acid with small decrease of activity. The catalyst reused in the Suzuki reaction was characterized using transmission electron microscopy, vibrating sample magnetometry and X‐ray photoelectron spectroscopy. Using experiments such as hot filtration and poisoning tests, it has been shown that the true catalyst works under homogeneous conditions according to the release–return pathway of active palladium species.     

Cross‐coupling reactions in water using ionic liquid‐based palladium(II)–phosphinite complexes as outstanding catalysts

Two new phosphinite ligands based on ionic liquids [(Ph₂PO)C₇H₁₄N₂Cl]Cl ( 1 ) and [(Cy₂PO)C₇H₁₄N₂Cl]Cl ( 2 ) were synthesized by reaction of 1‐(3‐chloro‐2‐hydoxypropyl)‐3‐methylimidazolium chloride, [C₇H₁₅N₂OCl]Cl, with one equivalent of chlorodiphenylphosphine or chlorodicyclohexylphosphine, respectively, in anhydrous CH₂Cl₂ and under argon atmosphere. The reactions of 1 and 2 with MCl₂(cod) (M = Pd, Pt; cod = 1,5‐cyclooctadiene) yield complexes cis‐[M([(Ph₂PO)C₇H₁₄N₂Cl]Cl)₂Cl₂] and cis‐[M(Cy₂PO)C₇H₁₄N₂Cl]Cl)₂Cl₂], respectively. All complexes were isolated as analytically pure substances and characterized using multi‐nuclear NMR and infrared spectroscopies and elemental analysis. The catalytic activity of palladium complexes based on ionic liquid phosphinite ligands 1 and 2 was investigated in Suzuki cross‐coupling. They show outstanding catalytic activity in coupling of a series of aryl bromides or aryl iodides with phenylboronic acid under the optimized reaction conditions in water. The complexes provide turnover frequencies of 57 600 and 232 800 h^?1 in Suzuki coupling reactions of phenylboronic acid with p‐bromoacetophenone or p‐iodoacetophenone, respectively, which are the highest values ever reported among similar complexes for Suzuki coupling reactions in water as sole solvent in homogeneous catalysis. Furthermore, the palladium complexes were also found to be highly active catalysts in the Heck reaction affording trans‐stilbenes. Copyright © 2014 John Wiley & Sons, Ltd.     

N‐functionalized azolin‐2‐ylidene‐palladium‐catalyzed heck reaction

Novel 1,3‐dialkylimidazolidinium, 1,3‐dialkyl‐3,4,5,6‐tetrahydropyrimidinium, and 1,3‐dialkyl‐1H‐4,5,6,7‐tetrahydrodiazepinium hexafluorophosphates ( 1a–c, 2a–c ) as N‐heterocyclic carbene precursors have been synthesized and characterized. The incorporation of saturated N‐heterocyclic carbenes into palladium precatalysts gives high‐catalyst activity in the Heck coupling of aryl bromide substrates in aqueous media. The complexes were generated in the presence of Pd(OAc)₂ by in situ deprotonation of 1,3‐dialkylazolinium salts 1, 2 . © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:82–86, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20415     

Well‐Defined N‐Heterocyclic Carbene‐Palladium Complexes as Efficient Catalysts for Domino Sonogashira Coupling/Cyclization Reaction and C‐H bond Arylation of Benzothiazole

Well‐defined and air‐stable PEPPSI (Pyridine Enhanced Precatalyst Preparation Stabilization and Initiation) themed palladium bis‐N‐heterocyclic carbene complexes have been developed for the domino Sonogashira coupling/cyclization reaction of 2‐iodophenol with a variety of terminal alkynes and C‐H bond arylation of benzothiazole with aryl iodides. The PEPPSI themed palladium complexes, 2a and 2b were synthesized in good yields from the reaction of corresponding imidazolium salts with PdCl₂ and K₂CO₃ in pyridine. The new air‐stable palladium‐NHC complexes were characterized by NMR spectroscopy, X‐ray crystallography, elemental analysis, and mass spectroscopy studies. The PEPPSI themed palladium(II) bis‐N‐heterocyclic carbene complexes 2a and 2b exhibited excellent catalytic activities for domino Sonogashira coupling/cyclization reaction of 2‐iodophenol with terminal alkynes yielding benzofuran derivatives. In addition, the palladium complexes, 2a and 2b successfully catalyzed the direct C‐H bond arylation of benzothiazole with aryl iodides as coupling partners in presence of CuI as co‐catalyst.     

Application of N,N‐bis(diphenylphosphino)aniline palladium(II) complexes as pre‐catalysts in Heck coupling reactions

Palladium(II) complexes with N,N‐bis(diphenylphosphino)aniline ligands catalyse the Heck reaction between styrene and aryl bromides, affording stilbenes in good yield. The structures of two of the complexes used as pre‐catalysts have been determined by single‐crystal X‐ray diffraction. Copyright © 2007 John Wiley & Sons, Ltd.     

Silica‐coated nano‐Fe3O4‐supported iminopyridine palladium complex as an active,phosphine‐free and magnetically separable catalyst for Heck reactions

A novel magnetic nanoparticle‐supported iminopyridine palladium complex was successfully prepared by attaching palladium acetate to iminopyridine ligand‐functionalized silica‐coated nano‐Fe₃O₄. The as‐prepared catalyst was well characterized and was evaluated in Heck reactions in terms of activity and recyclability. It was found to be highly efficient for the reactions of various aryl iodides and aryl bromides having electron‐withdrawing groups with olefins under phosphine‐free and inert atmosphere‐free conditions. Moreover, the catalyst could be conveniently recovered using an external magnet, and the recyclability was influenced by the base in the Heck reaction. The catalyst could be reused at least six times with no significant loss in activity when triethylamine acted as the base.     

Chemo‐ and Regioselective C(sp3)H Arylation of Unactivated Allylarenes by Deprotonative Cross‐Coupling

The combination of aryl bromides, allylbenzene, base and a palladium catalyst usually results in a Heck reaction. Herein we combine these same reagents, but override the Heck pathway by employing a strong base. In the presence of LiN(SiMe₃)₂, allylbenzene derivatives undergo reversible deprotonation. Transmetalation of the resulting allyllithium intermediate to LPdAr(Br) and reductive elimination provide the 1,1‐diarylprop‐2‐enes, which are not accessible by the Heck reaction. The regioselectivity in this deprotonative cross‐coupling process is catalyst‐controlled and very high.     

Phosphine-Free Tetradentate Salicylaldimine Ligand Complexed with Palladium: First Application in Heck Reactions

Heck reactions were carried out using phosphine-free tetradentate salicylaldimine ligand complexed with PdCl₂ under mild reaction conditions, short reaction time, and low palladium loading. All aryl iodides underwent coupling reactions with olefins, giving corresponding trans-products, with good to excellent yields, whereas aryl bromides gave very poor yields and aryl chlorides failed to react.     

Multicomponent,Flow Diazotization/Mizoroki–Heck Coupling Protocol: Dispelling Myths about Working with Diazonium Salts

A single pass flow diazotization/Mizoroki–Heck protocol has been developed for the production of cinnimoyl and styryl products. The factors that govern aryl diazonium salt stability have been examined in detail leading to the development of a MeOH/DMF co‐solvent system in which the diazonium salts can be generated in the presence of all other reaction components and then coupled selectively to give the desired products. Finally the key role of the reaction quench for flow reactions has been demonstrated.     

Facile Access to cis‐2,6‐Disubstituted Tetrahydropyrans by Palladium‐Catalyzed Decarboxylative Allylation: Total Syntheses of (±)‐Centrolobine and (+)‐Decytospolides A and B

cis‐2,6‐Tetrahydropyran is an important structural skeleton of bioactive natural products. A facile synthesis of cis‐2,6‐disubstituted‐3,6‐dihydropyrans as cis‐2,6‐tetrahydropyran precursors has been achieved in high regio‐ and stereoselectivity with high yields. This reaction involves a palladium‐catalyzed decarboxylative allylation of various 3,4‐dihydro‐2H‐pyran substrates. Extending this reaction to 1,2‐unsaturated carbohydrates allowed the achievement of challenging β‐C‐glycosylation. Based on this methodology, the total syntheses of (±)‐centrolobine and (+)‐decytospolides A and B were achieved in concise steps and overall high yields.     

Fe‐catalyzed hydrohalogenative cyclization of cyclohexadienone‐containing enynes

A Fe‐catalyzed hydrohalogenative cyclization of cyclohexadienone‐containing 1,n‐enynes to give three different types of compounds is discussed. 1,6‐enynes with a stoichiometric amount of FeX₃ provided cis‐hydrobenzofurans with moderate stereoselectivity, whereas the reaction with TMSX (X = Cl, Br) as the halide source in the presence of Fe catalyst improved the stereoselectivity of halide addition highly. The alkyl vs aryl shows difference that the reaction of 1,6‐enynes bearing an alkylethynyl group gave meta alkenated phenols (2 examples) whereas a similar reaction of 1,6‐enynes with an arylethynyl group delivered only cis‐hydrobenzofurans (12 examples). 1,7‐enynes afforded tricyclic products (4 examples). The different reactivity of 1,6‐ and 1,7‐enynes is probably influenced by the formation of a six‐membered chair‐like intermediate in 1,6‐enynes.     

Heck reactions of 2-substituted enol ethers with aryl bromides catalysed by a tetraphosphine/palladium complex

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyses the Heck reaction of β-substituted enol ethers with aryl bromides. Employing β-methoxystyrene, 3-ethoxyacrylonitrile or methyl 3-methoxyacrylate, the regioselective α-arylation of these enol ethers was observed in all cases, and mixtures of Z and E isomers were generally obtained, which in many cases yielded a single ketone product after acid treatment. The stereoselectivity of this reaction depends on steric and electronic factors, and better stereoselectivities in favour of Z isomers were observed with electron-rich or sterically congested aryl bromides. Better yields were obtained for this reaction with electron-rich or sterically congested aryl bromides than with electron-poor aryl bromides. This observation suggests that with these β-substituted enol ethers the rate-limiting step of the catalytic cycle is not the oxidative addition of the aryl bromide to the palladium complex.     

The synthesis of non‐symmetrical stilbene analogs of trans‐resveratrol using the same Pd catalyst in a sequential double‐Heck arylation of ethylene

We have developed a sequential and selective Pd‐catalyzed double‐Heck arylation of ethylene that results in non‐symmetrical nitro‐stilbene analogs of trans‐resveratrol at excellent yields. A catalytic system consisting of Pd(OAc)₂ and P(o‐tolyl)₃ permitted us to carry out the two consecutive Heck arylations without losing activity from the first to the second Heck reaction. After the first Heck arylation of ethylene, no isolation or additional catalyst loading is required for the second Heck arylation reaction. This protocol was applied to the synthesis of methylated trans‐resveratrol, which was obtained at a 65% overall yield. Copyright © 2011 John Wiley & Sons, Ltd.     

A Simple and Efficient Synthesis of Ethyl 1‐Aryl‐4‐formyl‐1H‐pyrazole‐3‐carboxylates

A new simple and convenient method of synthesis of ethyl 1‐aryl‐4‐formyl‐1H‐pyrazole‐3‐carboxylates from aromatic amines via diazonium salts has been developed. Hydrolysis and hydrazinolyization of these compounds has been investigated.     

Guanidine‐Functionalized Resin‐Supported Pd(0) Catalyst: Activity,Reusability, and Redeposition of Active Pd Species in Heck Vinylation

The guanidine‐functionalized resin‐supported Pd(0) catalyst [GDR·Pd(0)] is highly active in Heck reaction of aryl bromides with acrylic acid or styrene without the need to exclude air. The catalyst can be recycled at least 9 times without significant loss of activity in N‐methyl‐2‐pyrrolidone at 140 °C. The Heck reaction proceeds homogeneously with dissolved palladium species and the dissolved active palladium species can redeposit onto the surface of catalyst in the reaction. The XRD peak shifting of Pd phases in the catalyst provides the evidence for the re‐deposition of the active palladium species.     

Investigation of the Catalytic Activity of a 2‐Phenylidenepyridine Palladium(II) Complex Bearing 4,5‐Dicyano‐1,3‐bis(mesityl)imidazol‐2‐ylidene in the Mizoroki‐Heck Reaction

The phenylidenepyridine (ppy) palladacycles [PdCl(ppy)(IMes)] ( 4 ) [IMes = 1,3‐bis(mesityl)imidazol‐2‐ylidene] and [PdCl(ppy){(CN)₂IMes}] ( 6 ) [(CN)₂IMes = 4,5‐dicyano‐1,3‐bis(mesityl)imidazol‐2‐ylidene] were prepared by facile two step syntheses, starting with the reaction of palladium(II) chloride with 2‐phenylpyridine followed by subsequent addition of the NHC ligand to the precatalyst precursor [PdCl(ppy)]₂. Suitable crystals for the X‐ray analysis of the complexes 4 and 6 were obtained. It was shown that 6 has a shorter NHC‐palladium bond than the IMes complex 4 . The difference of the palladium carbene bond lengths based on the higher π‐acceptor strength of (CN)₂IMes in comparison to IMes. Thus, (CN)₂IMes should stabilize the catalytically active central palladium atom better than IMes. As a measure for the π‐acceptor strength of (CN)₂IMes compared to IMes, the selone (CN)₂IMes · Se ( 7 ) was prepared and characterized by ⁷⁷Se‐NMR spectroscopy. The π‐acceptor strength of 7 was illuminated by the shift of its ⁷⁷Se‐NMR signal. The ⁷⁷Se‐NMR signal of 7 was shifted to much higher frequencies than the ⁷⁷Se‐NMR signal of IMes · Se. Catalytic experiments using the Mizoroki‐Heck reaction of aryl chlorides with n‐butyl acrylate showed that 6 is the superior performer in comparison to 4 . Using complex 6 , an extensive substrate screening of 26 different aryl bromides with n‐butyl acrylate was performed. Complex 6 is a suitable precatalyst for para‐substituted aryl bromides. The catalytically active species was identified by mercury poisoning experiments to be palladium nanoparticles.