Copper-catalyzed cross-coupling of functionalized alkyl halides and tosylates with secondary and tertiary alkyl grignard reagents

Added value: A copper-based method is highly efficient for the cross-coupling of alkyl electrophiles with secondary and tertiary alkyl Grignard reagents. The method is distinguished by its broad substrate scope and high functional group tolerance.     

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.     

Iron-catalyzed cross-coupling of aryltrimethylammonium triflates and alkyl Grignard reagents

Fe(acac)₃ effectively catalyzes reaction of aryltrimethylammonium triflates with β-hydrogen-containing primary or secondary alkyl Grignard reagents in a mixed solvent of THF and NMP at room temperature. A series of functional groups are tolerated under the reaction conditions.     

Iron-catalyzed cross-coupling of alkenyl sulfides with Grignard reagents

[reaction: see text] The iron-catalyzed cross-coupling reaction of alkenyl sulfides with Grignard reagents is described. While the cross-coupling proceeds efficiently at alkenyl-S bonds, almost no cross-coupling takes place at aryl-S bonds, attesting to a unique selectivity of iron catalysis. The beneficial effect of potentially coordinating 2-pyrimidyl group on sulfur is also described.     

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.     

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]     

Cross-couplings of alkyl halides with heteroaromatic halides, in water at room temperature

Zn-mediated, Pd-catalyzed cross-coupling reactions between heteroaromatic and alkyl halides can be done at room temperature in pure water using a commercially available Pd catalyst and PTS, a nanomicelle-forming amphiphile. Notably, zinc metal inserts selectively into a carbon sp³-halide bond, while palladium adds oxidatively to a carbon sp²-bond.     

Ionic liquids as reagents and solvents in conjunction with microwave heating: rapid synthesis of alkyl halides from alcohols and nitriles from aryl halides

We show that using ionic liquids as reagents in conjunction with microwave heating it is possible to prepare primary alkyl halides from the corresponding alcohols rapidly. Using ionic liquids as solvents in conjunction with microwave heating it is possible to prepare aryl nitriles from the corresponding aryl bromides or iodides. The scope and limitations of using microwave-promotion as a tool in these reactions is discussed.     

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.     

Synthesis of nickel-salicylideneimines complexes and catalyzing cross-coupling reaction of aryl halides and Grignard reagents

A series of nickel-salicylideneimines complexes were prepared in wild way and these complexes were stable to air and moisture. The nickel-salicylideneimines complexes exhibited good activity in catalyzing Grignard reagents with aryl halids to biphenyl derivatives and the more fluorine atoms contained by N-substituted benzene moiety could function the better activity.     

Nickel-catalyzed cross-coupling reaction of grignard reagents with alkyl halides and tosylates: remarkable effect of 1,3-butadienes

A new method for the cross-coupling reaction of Grignard reagents with alkyl chlorides, bromides, and tosylates has been developed by the use of a nickel catalyst in the presence of a diene as an additive. This reaction proceeds efficiently at 0-25 degrees C in THF using primary and secondary alkyl and aryl Grignard reagents. Nickel complexes bearing no phosphine ligands, such as NiCl2, Ni(acac)2, and Ni(COD)2, afford the coupling products in good yields, whereas NiCl2(PPh3)2 and NiCl2(dppp) were less effective. 1,3-Butadiene shows the highest activity as an additive for the present coupling reaction. A plausible reaction pathway was proposed.