Sonogashira reaction of aryl halides with propiolaldehyde diethyl acetal catalyzed by a tetraphosphine/palladium complex

All-cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyzes the Sonogashira reaction of propiolaldehyde diethyl acetal with a variety of aryl bromides and chlorides. A minor electronic effect of the substituents of the aryl bromide was observed. Similar reaction rates were observed in the presence of activated aryl bromides such as 4-trifluoromethylbromobenzene and deactivated aryl bromides such as bromoanisole. Turnover numbers up to 95,000 can be obtained for this reaction. Even aryl chlorides and heteroarylbromides or chlorides have been successfully alkynylated with this catalyst. Moreover, a wide variety of substituents on the aryl halide such as fluoro, trifluoromethyl, acetyl, benzoyl, formyl, nitro, dimethylamino or nitrile are tolerated.     

Heck reactions of aryl bromides 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 bromides. In the presence of hex-1-en-3-ol or oct-1-en-3-ol, the β-arylated carbonyl compounds were selectively obtained. Linalool and 2-methylbut-3-en-2-ol led to the corresponding 1-arylalk-1-en-3-ol derivatives. Turnover numbers up to 69,000 can be obtained for this reaction. A minor electronic effect of the substituents of the aryl bromide was observed. Similar reaction rates were observed in the presence of activated aryl bromides such as bromoacetophenone and deactivated aryl bromides such as bromoanisole.     

Tetraphosphine/palladium catalysed Suzuki cross-coupling reactions of aryl halides with alkylboronic acids

Through the use of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides and chlorides undergoes Suzuki cross-coupling with alkylboronic acids in good yields. Several alkyl substituents such as ethyl, n-butyl, n-octyl, isobutyl or 2,2-dimethylpropyl on the alkylboronic acids have been successfully used. The functional group tolerance on the aryl halide is remarkable; substituents such as fluoro, methyl, methoxy, acetyl, formyl, benzoyl, nitro or nitrile are tolerated. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides.     

Coupling reactions of aryl bromides with 1-alkynols catalysed by a tetraphosphine/palladium catalyst

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ system catalyses efficiently the coupling reactions of aryl halides with a variety of alkynols such as propargyl alcohol, but-1-yn-4-ol, pent-1-yn-5-ol or hex-1-yn-6-ol. The catalyst can be used at low loading. Higher reaction rates were observed in the presence of but-1-yn-4-ol, pent-1-yn-5-ol or hex-1-yn-6-ol than with propargyl alcohol. The protection of the alcohol functions as an ether or a silyloxy group led generally to similar or better results than the reactions performed with the unprotected alcohols.     

Synthesis of β-aryl ketones by tetraphosphine/palladium catalysed Heck reactions of 2- or 3-substituted allylic alcohols with aryl bromides

Through the use of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides undergoes Heck reaction using 2- or 3-subtituted allylic alcohols. With these sterically congested alkenes, the selective formation of β-aryl ketones was observed when appropriate reaction conditions were used. The influence of the functional group on the aryl bromide and of the base on the selectivity is remarkable. With several substrates, much higher selectivities were obtained using NaHCO₃ instead of K₂CO₃ as base. Furthermore, this catalyst can be used at low loading with several substrates.     

Heck arylations of pent-4-enoates or allylmalonate using a palladium/tetraphosphine catalyst

The Heck reaction of aryl halides with functionalised alk-1-enes should be a powerful method for the synthesis of functionalised (E)-1-arylalk-1-ene derivatives. The major problem of this reaction is the palladium-catalysed migration of the carbon-carbon double bond along the alkyl chain when there are no substituents on the C3 carbon of the alk-1-enes. We observed that for the arylation of ethyl pent-4-enoate, ethyl 2-methylpent-4-enoate or dimethyl allylmalonate this migration could be partially or completely controlled using appropriate reaction conditions. The ramification on the alkyl chain and the substituents on the aryl halide have also an important influence on this migration. Moreover, the cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/1/2[PdCl(C₃H₅)]₂ system catalyses this reaction with a wide range of aryl bromides using very high ratio substrate/catalyst in good yields.     

Direct arylation of oxazole and benzoxazole with aryl or heteroaryl halides using a palladium-diphosphine catalyst

Through the use of PdCl(dppb)(C₃H₅) as a catalyst, a range of aryl bromides and chlorides undergoes coupling via C-H bond activation/functionalization reaction with oxazole or benzoxazole in good yields. This air-stable catalyst can be used at low loadings with several substrates. Surprisingly, better results in terms of substrate/catalyst ratio were obtained in several cases using electron-excessive aryl bromides than with the electron-deficient ones. This seems to be mainly due to the relatively low thermal stability of some of the 2-arylbenzoxazoles formed with electron-deficient aryl halides. With these substrates, in order to obtain higher yields of product, the reactions had to be performed at a lower temperature (100-120 °C) using a larger amount of catalyst. On the other hand, in the presence of the most stable products, the reactions were performed at 150 °C using as little as 0.2 mol% catalyst. Arylation of benzoxazole with heteroaryl bromides also gave the coupling products in moderate to high yields using 0.2-5 mol% catalyst. With this catalyst, electron-deficient aryl chloride such as 4-chlorobenzonitrile, 4-chloroacetophenone or 2-chloronitrobenzene have also been used successfully.     

A new palladium catalyzed protocol for atom-efficient cross-coupling reactions of triarylbismuths with aryl halides and triflates

A new palladium catalyzed protocol for an atom-efficient cross-coupling reaction of triarylbismuths with aryl halides and triflates has been described. The palladium catalytic system with Cs₂CO₃ base was found to be very efficient in DMA solvent to furnish excellent yields of cross-coupled functionalized biaryls in short reaction times.     

Suzuki-Miyaura cross-coupling of aryl and alkyl halides using palladium/imidazolium salt protocols

A simple new protocol for the high yielding Suzuki-Miyaura cross-couplings of aryl chlorides with aryl boronic acids using a palladium/imidazolium salt catalytic system is presented. The first examples of a palladium/imidazolium salt protocol for sp³-sp³ Suzuki-Miyaura couplings of alkyl halides are also disclosed.     

An efficient palladium-catalyzed Heck coupling of aryl chlorides with alkenes

Catalyst system PdCl₂(PCy₃)₂/Cs₂CO₃ in dioxane was found to be the efficient catalyst system for Heck cross-coupling reactions of deactivated, neutral, and activated aryl chlorides with a variety of alkenes under mild conditions to afford selectively E-arylated alkenes in good to excellent yields.     

Heck reaction of aryl halides with linear or cyclic alkenes catalysed by a tetraphosphine/palladium catalyst

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ system catalyses efficiently the Heck reaction of aryl halides with linear alkenes such as pent-1-ene, oct-1-ene or dec-1-ene. Selectivities up to 70% in favour of E-1-arylalk-1-ene isomers can be obtained. In the presence of cyclic alkenes the selectivities of the reactions strongly depends on the ring size. Addition to cyclohexene or cycloheptene led mainly to 1-arylcycloalk-3-ene derivatives. On the other hand, addition to cyclooctene led to 1-arylcycloalk-1-ene adducts.     

Tetraphosphine/palladium-catalyzed Heck reactions of aryl halides with disubstituted alkenes

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyses the Heck reaction of disubstituted alkenes such as methyl crotonate, ethyl cinnamate, methyl methacrylate or α-methylstyrene with a variety of aryl halides. In the presence of 1,2-disubstituted alkenes the stereoselectivities of the reactions strongly depend on the substituents of the alkenes. Selectivities up to 97% in favor of E-isomers can be obtained for the addition to methyl crotonate. With the 1,1-disubstituted alkenes methyl methacrylate or α-methylstyrene mixtures of products are obtained.     

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.     

Palladium-catalyzed highly regioselective Heck reaction of aryl nonaflates with electron-rich olefins

Highly efficient palladium-catalyzed Heck coupling of aryl nonaflates with electron-rich vinyl ethers, and enamides is described. These reactions afforded exclusively the branched products in good yields. The results indicated that aryl nonaflates are effective alternative to the frequently employed aryl triflates.     

Expedient synthesis of novel β-ketoesters from the Mizoroki–Heck coupling of ethyl 3-ethoxyacrylate with aryl and pyridyl halides

It is well known that β-ketoesters are useful intermediates for the synthesis of a range of heterocyclic templates. While there are many useful synthetic methods available to access these intermediates, there are still opportunities for the discovery of useful methodologies for their construction from novel starting materials. In this regard, we report on the discovery of a facile Pd-catalyzed Mizoroki–Heck coupling of ethyl 3-ethoxyacrylate with aryl and heteroaryl halides to form substituted alkoxyacrylates which can be hydrolyzed to form novel aryl and heteroaryl β-ketoesters.     

Sonogashira cross-coupling reactions of aryl chlorides with alkynes catalysed by a tetraphosphine-palladium catalyst

A range of aryl chlorides undergoes cross-couplings with alkynes in good yields in the presence of [PdCl(C₃H₅)]₂/cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as catalyst. A variety of aryl chlorides such as chloroacetophenone, chlorobenzonitrile, chloronitrobenzene, chloroanisole or chlorotoluene have been used successfully. The reaction also tolerates several alkynes such as phenylacetylene, dec-1-yne, ethynylcyclohexene or alk-1-ynols. Furthermore, this catalyst can be used at low loading with some substrates.     

Design of highly active heterogeneous palladium catalysts for the activation of aryl chlorides in Heck reactions

In situ generation of highly active palladium species by intermediate dissolution of Pd from solid supported catalysts has been demonstrated to be a very successful approach for the activation of aryl chlorides in Heck reactions. The new ‘heterogeneous’ Pd catalysts act as reservoir for molecular Pd species with unsaturated coordination sphere in solution. Crucial Pd leaching and re-deposition onto the support can be controlled by optimization of reaction conditions and by the properties of the catalysts. Pd is re-deposited onto the support at the end of the reaction. The catalysts, palladium supported on activated carbon, on various metal oxides or fluorides and Pd complexes in zeolites, are easy to prepare, though the preparation conditions are crucial. The catalysts convert all aryl bromides completely within minutes (TON 100,000). Aryl chlorides (even deactivated ones) are converted with high yields, within 2-6 h. The catalysts belong to the most active ones in Heck reactions at all (including best homogeneous systems) and fulfill all relevant requirements for practical applications in laboratory and industry.     

Chemoselective Heck arylation of acrolein diethyl acetal catalyzed by an oxime-derived palladacycle

A dimeric 4-hydroxyacetophenone oxime-derived palladacycle has been used as a very efficient precatalyst for the chemoselective arylation of acrolein diethyl acetal to give either cinnamaldehyde derivatives or 3-arylpropanoate esters by proper choice of the reaction conditions. The synthesis of cinnamaldehyde derivatives can be performed by Heck reaction of acrolein diethyl acetal with iodo-, bromo- or chloroarenes in N,N-dimethylacetamide (DMA) using K₂CO₃ as base at 120 °C and tetra-n-butylammonium acetate (TBAA) and KCl as additives, followed by acid workup. In the case of 3-arylpropanoate esters the corresponding arylation of acrolein diethyl acetal with iodoarenes can be performed at 90 °C in aqueous DMA using (dicylohexyl)methylamine as base, whereas for bromoarenes the reaction has to be performed at 120 °C using tetra-n-butylammonium bromide (TBAB) as additive. Alternatively, this process can be performed under microwave irradiation. These couplings take place in good yields and with lower catalyst loading than with palladium(II) acetate as well as in shorter reaction times and with lower excess of acrolein diethyl acetal.     

Selective synthesis of (E)-triethyl(2-arylethenyl)silane derivatives by reaction of aryl bromides with triethyl vinylsilane catalysed by a palladium-tetraphosphine complex

Cis, cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane / 0.5 [PdCl(C₃H₅)]₂ system catalyses the Heck reaction of vinylsilane derivatives with a range of aryl bromides with high ratio substrate/catalyst in good yields. The formation of mixtures of styrene, (E)-triethyl(2-arylethenyl)silane and triethyl(1-arylethenyl)silane derivatives was observed in some cases. Very high selectivities (up to 100%) in favour of the formation of (E)-triethyl(2-arylethenyl)silane derivatives were obtained in the presence of sodium acetate as base. With other bases such as potassium carbonate, the formation of large amounts of styrene derivatives was observed. The reaction tolerates several functions such as fluoro, trifluoromethyl, methoxy, dimethylamino, acetyl, formyl, benzoyl, carboxylate, nitro or nitrile. Moreover, turnover numbers up to 10,000 can be obtained for this reaction.     

Unsymmetric-1,3-disubstituted imidazolium salt for palladium-catalyzed Suzuki–Miyaura cross-coupling reactions of aryl bromides

A series of 1-(ferrocenylethyl)-3-substituted-imidazolium salts [3-substitute = 2,6-di(iso-propyl)phenyl (1a), 2,4,6-trimethylphenyl (1b), tert-butyl (1c), 1-Ad (1d), cyclohexyl (1e)] have been synthesized from a racemic ferrocenylethyl acetate and the corresponding N-substituted imidazole in high yields (70–94%). A combination of Pd(OAc)₂ and 1a–d was found to form an excellent catalyst system for the Suzuki–Miyaura cross-coupling reactions of aryl bromides with phenylboronic acid in the presence of Cs₂CO₃.