Iron(III) salen-type catalysts for the cross-coupling of aryl Grignards with alkyl halides bearing beta-hydrogens

Iron(III) salen and related complexes are active catalysts for the coupling, under mild and simple reaction conditions, of aryl Grignard reagents with primary and secondary alkyl halide substrates bearing beta-hydrogens.     

Iron-catalyzed Grignard cross-coupling with alkyl halides possessing beta-hydrogens

Tris(acetylacetonato)iron(III) (Fe(acac)(3)) was found to be an efficient catalyst for the cross-coupling reaction between aryl Grignard reagents and alkyl halides possessing beta-hydrogens. The reaction is applicable to secondary alkyl halides as well as primary ones. [reaction: see text]     

Iron-catalyzed cross-coupling of primary and secondary alkyl halides with aryl grignard reagents

An iron-catalyzed cross-coupling reaction of a primary or secondary alkyl halide with an aryl Grignard reagent proceeds under mild conditions to give the corresponding coupling product in quantitative yield.     

Catalysts for cross-coupling reactions with non-activated alkyl halides

Despite the problems inherent to metal-catalyzed cross-coupling reactions with alkyl halides, these reactions have become increasingly important during the last few years. Detailed mechanistic investigations have led to a variety of novel procedures for the selective cross-coupling of non-activated alkyl halides bearing beta hydrogen atoms with a variety of organometallic nucleophiles under mild reaction conditions. This Minireview highlights selected examples of metal-catalyzed coupling methods and is intended to encourage chemists to exploit the potential of these approaches in organic synthesis.     

An iron-containing ionic liquid as recyclable catalyst for aryl grignard cross-coupling of alkyl halides

[reaction: see text] The ionic liquid butylmethylimidazolium tetrachloroferrate (bmim-FeCl(4)) was found to be a very effective and completely air stable catalyst for the biphasic Grignard cross-coupling with primary and secondary alkyl halides bearing beta-hydrogens. After simply decanting the product in the ethereal layer, the ionic liquid catalyst was successfully recycled four 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.     

Pd-catalyzed cross-coupling reactions of alkyl halides

Cross-coupling reactions have become indispensable tools for creating carbon-carbon (or heteroatom) bonds in organic synthesis. Like in other important transition metal catalyzed reactions, such as metathesis, addition, and polymerization, unsaturated compounds are usually employed as substrates for cross-coupling reactions. However during the past decade, a great deal of effort has been devoted to the use of alkyl halides as saturated compounds in cross-coupling reactions, which has resulted in significant progress in this undeveloped area by introducing new effective ligands. Many useful catalytic systems are now available for synthetic transformations based on C(sp(3))-C(sp(3)), C(sp(3))-C(sp(2)) and C(sp(3))-C(sp) bond formation as complementary methods to conventional C(sp(2))-C(sp(2)), C(sp(2))-C(sp) and C(sp)-C(sp) coupling. This tutorial review summarizes recent advances in cross-coupling reactions of alkyl halides and pseudohalides catalyzed by a palladium complex.     

Palladium-catalysed cross-coupling of 2-trimethylsilylpyridine with aryl halides

Palladium-catalysed cross-coupling of 2-trimethylsilylpyridine with aryl halides in the presence of stoichiometric silver(I) oxide, and catalytic TBAF allows the rapid preparation of the corresponding pyridin-2-ylaryl compounds in moderate to good yields under mild thermal conditions.     

Cobalt-catalyzed cross-coupling reactions of alkyl halides with aryl Grignard reagents and their application to sequential radical cyclization/cross-coupling reactions

Reactions of alkyl halides with arylmagnesium bromides in the presence of cobalt(II)(diphosphine) complexes are discussed. Treatment of 1-bromooctane with phenylmagnesium bromide with the aid of a catalytic amount of CoCl₂(dppp) [DPPP=1,3-bis(diphenylphosphino)propane] yielded octylbenzene in good yield. The reaction mechanism would include single electron transfer from an electron-rich cobalt complex to alkyl halide to generate the corresponding alkyl radical. The mechanism was justified by CoCl₂(dppe)-catalyzed [DPPE=1,2-bis(diphenylphosphino)ethane] sequential radical cyclization/cross-coupling reactions of 6-halo-1-hexene derivatives that yielded benzyl-substituted cyclopentane skeletons.     

Manganese-catalyzed cross-coupling reactions of aliphatic amines with aryl halides

An efficient and convenient protocol has been developed for the N-arylation of aliphatic amines with differently substituted aryl halides using a MnCl₂·4H₂O/l-proline catalyst and NaOt-Bu as the base in DMSO.     

Iron(II) complexes with functionalized amine-pyrazolyl tripodal ligands in the cross-coupling of aryl Grignard with alkyl halides

Structurally distinctive Fe(II) complexes with furan, thiophene and pyridine functionalized amine-pyrazolyl tripodal hybrid ligands have been synthesized and crystallographically characterized. The tether substituent at the central amine plays an active role in determining the coordination mode of the ligand and the metal geometry. All complexes are catalytically active towards cross-coupling of aryl Grignard reagents with primary and secondary alkyl halides with β-hydrogen under ambient conditions. ESI-MS spectra analysis revealed the ligand-stabilised Fe(II) and Mg(II) species.     

Nickel-catalyzed reductive cross-coupling of unactivated alkyl halides

A Ni-catalyzed reductive approach to the cross-coupling of two unactivated alkyl halides has been successfully developed. The reaction works efficiently for primary and secondary halides, with at least one being bromide. The mild reaction conditions allow for excellent functional group tolerance and provide the C(sp(3))-C(sp(3)) coupling products in moderate to excellent yields.     

Silver-catalyzed cross-coupling reactions of alkyl bromides with alkyl or aryl Grignard reagents

Treatment of secondary or tertiary alkyl bromides with alkyl Grignard reagents in the presence of catalytic amounts of silver bromide and potassium fluoride in CH₂Cl₂ afforded the corresponding cross-coupling products in reasonable yields. Moreover, silver showed catalytic activity for the cross-coupling reactions of alkyl bromides with aryl Grignard reagents.     

Negishi cross-coupling of secondary alkylzinc halides with aryl/heteroaryl halides using Pd-PEPPSI-IPent

Pd-PEPPSI-IPent has proven to be an excellent catalyst for the Negishi cross-coupling reaction of secondary alkylzinc reagents with a wide variety of aryl/heteroaryl halides. Importantly, β-hydride elimination/migratory insertion of the organometallic leading to the production of isomeric coupling products has been significantly reduced using the highly-hindered Ipent ligand.     

Palladium-catalyzed cross-coupling of cyclopropanols with aryl halides under mild conditions

Intra- and intermolecular palladium-catalyzed cross-coupling of cyclopropanols with aryl halides can be achieved in good yields under mild conditions.     

N-heterocyclic carbene-catalyzed cross-coupling of aromatic aldehydes with activated alkyl halides

N-Heterocyclic carbene-catalyzed umpolung of aldehydes followed by their interception with diarylbromomethanes has been reported. This conceptually novel transition-metal-free cross-coupling of aldehydes with alkyl halides works well at low catalyst loadings and under mild reaction conditions leading to the formation of diaryl acetophenone derivatives in good yields. In addition, α-halo ketones and esters can also be used as aldehyde reaction partners.     

Palladium-catalyzed cross-coupling of benzyl thioacetates and aryl halides

A method for preparing benzyl aryl thioethers utilizing an in situ deprotection of benzyl thioacetates as an alternative to free thiols as starting materials has been developed and optimized. Good to excellent yields of diverse benzyl aryl thioethers are obtained with air-stable, odor-free, and easy to prepare thioesters. A one-pot protocol for forming benzyl aryl thioethers from a benzyl halide, potassium thioacetate, and an aryl bromide has also been demonstrated.     

Palladium-catalyzed cross-coupling reaction of tricyclopropylbismuth with aryl halides and triflates

The palladium-catalyzed cross-coupling reaction of tricyclopropylbismuth with aryl and heterocyclic halides and triflates is reported. The reaction tolerates numerous functional groups and does not require anhydrous conditions. The method was successfully extended to the cross-coupling of triethylbismuth.