Search

When appropriate reaction conditions are used, very high yields of (E)-l-arylalk-1-en-3-one derivatives can be obtained by palladium-catalysed reactions of alk-1-en-3-ones with aryl bromides. The tetraphosphine cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane in combination with [Pd(C 3 H s )Cl] 2 was found to be a very efficient catalyst for this reaction. In general, higher reaction rates were observed with electron-poor aryl bromides, but the electron-rich aryl bromides 1-bromo-4-(dimethylamino)benzene and 4-bromoanisole also led to the arylated enones in high yields. Even with sterically very congested aryl bromides such as 9-bromoanthracene, 1-bromo-2,4,6-trimethylbenzene or l-bromo-2,4,6-triisopropylbenzene, the expected (E)-1-arylalk-l-en-3-ones were obtained in moderate to good yields. These enones appear to be unstable under the reaction conditions, and the addition of a small amount of hydroquinone to the reaction mixture was found to be crucial, especially for the vinylation of electron-deficient aryl bromides. A variety of alk-1-en-3-ones has been employed, and better results in terms of substrate/ catalyst ratios were obtained when oct-1-en-3-one or hex-1-en-3-one was used than when but-1-en-3-one or pent-1-en-3-one was used. It should be noted that several reactions can be performed with as little as 0.1-0.001 mol% catalyst.

A wide variety of 1,3-dienes have been prepared by the Heck vinylation of vinyl bromides using [Pd(η 3 -C 3 H 5 )Cl] 2 / CIS, CIS, CIS-1,2,3,4-tetrakis[(diphenylphosphino)methyl]cyclopentane (Tedicyp) as the catalyst precursor. Both α- and β-substituted vinyl bromides undergo the Heck reaction with functionalised alkenes such as acrylates, enones, styrenes or a vinyl sulfone, and also with nonfunctionalised alkenes such as dec-1-ene, leading stereoselectively, in most cases, to the corresponding E- or E, E-1,3-dienes in good yields. Furthermore, this catalyst can be used at low loading for several reactions.

Palladium associated with cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane (Tedicyp) was found to promote the direct 2-arylation of a variety of thiophene derivatives via CH functionalisation in good yields using very low catalyst loadings. Electron-deficient, electron-excessive or sterically-congested aryl bromides are tolerated. Moreover, several substituents on the aryl bromide or thiophene derivatives such as acetyl, formyl, nitrile, nitro, ester, methoxy, fluoro or trifluoromethyl are tolerated. The most reactive aryl bromides were coupled with thiophenes derivatives using as little as 0.1–0.01 mol % 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.

The tetraphosphine cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane in combination with [Pd(C 3 H 5 )Cl] 2 affords a very efficient catalyst for the Heck reaction of alk-1-en-3-ones with aryl bromides. If appropriate reaction conditions are used (NaOAc as base, hydroquinone as stabilising agent and DMF as solvent) high yields of (E)-1-aryl alk-1-en-3-one derivatives are obtained. In general, higher reaction rates were observed with electron-poor aryl bromides, but the electron-rich aryl bromides 4-N,N-dimethylaminobromobenzene and 4-bromoanisole also led to the arylated enones. Even with sterically very congested aryl bromides such as 9-bromoanthracene, 2,4,6-trimethylbromo-benzene or 2,4,6-triisopropylbromobenzene, the expected (E)-1-aryl alk-1-en-3-ones were obtained in moderate to good yields. Moreover, several reactions can be performed with as little as 0.1% catalyst.

The tetraphosphine all‐cis‐1,2,3,4‐tetrakis(diphenylphosphinomethyl)cyclopentane (Tedicyp) in combination with [Pd(C3H5)Cl]2 affords a very efficient catalyst for the coupling of cyclopropylboronic acid with aryl bromides and aryl chlorides. Higher reactions rates were observed with aryl bromides than with aryl chlorides; however, even in the presence of 1–0.4% of catalyst, a few aryl chlorides gave the coupling products in good yields. A wide variety of substituents such as alkyl, methoxy, trifluoromethyl, acetyl, benzoyl, formyl, carboxylate, nitro, and nitrile on the aryl halides are tolerated. The coupling reaction of sterically very congested aryl bromides such as bromomesitylene or 2,4,6‐triisopropylbromobenzene also proceeds in good yields.

All- cis -1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C 3 H 5 )] 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.

A system combining the tetraphosphine cis,cis,cis-1,2,3,4-tetrakis((diphenylphosphino)methyl)cyclopentane (Tedicyp) and [Pd(C3H5)Cl]2 was found to promote the direct arylation of furans via C−H functionalization in good yields using very low catalyst loadings.

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphanylmethyl)cyclopentane/[PdCl(C3H5)]2 efficiently catalyses the Heck reaction of α- and β-substituted enol ethers with aryl bromides. The arylation of 1-phenyl-1-(trimethylsilyloxy)ethylene led directly to the 2-aryl-1-phenylethanones. Similar reaction rates were observed with electron-rich, electron-deficient or sterically congested aryl bromides. Heck reaction with benzyl isopropenyl ether gave a mixture of isomers. However, this mixture gave selectively the 1-arylpropanones after hydrolysis. Employing β-methoxystyrene, 3-ethoxyacrylonitrile or methyl 3-methoxyacrylate, the regioselective α-arylation of these enol ethers was observed in all cases, but 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. Higher yields were obtained for this reaction with electron-rich or sterically congested aryl bromides than with electron-poor aryl bromides. These observations suggest that the rate-limiting step of the catalytic cycle is not the oxidative addition of the aryl bromide to the palladium complex with these substituted enol ethers.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

The tetraphosphine all-cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane in combination with [Pd(C 3 H 5 )Cl] 2 affords a very efficient catalyst for the alkynylation of aryl bromides with propargylamines. Higher reactions rates were observed with N,N-dialkylpropargylamines than with N-methylpropargylamine or propargylamine. A wide variety of substituents such as alkyl, phenyl, methoxy, dimethylamino, fluoro, trifluoromethyl, acetyl, benzoyl, formyl, carboxylate, nitro, or nitrile, on the aryl bromides are tolerated. High turnover numbers can be obtained with most of these aryl bromides. The coupling reaction of sterically very congested aryl bromides such as 9-bromoanthracene or 2,4,6-triisopropylbromobenzene also proceeds in good yields.

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 with acrolein ethylene acetal. With this acetal, the selective formation of 3-arylpropionic acids/esters was observed. 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.