Nickel-catalyzed cross-coupling reaction of alkynyl bromides with Grignard reagents

We describe a convenient method for the synthesis of 1,2-disubstituted acetylenes via a cross-coupling reaction of （bromoethynyl）benzene with Grignard reagents. The reaction of （bromoethynyl）benzene （1 mmol） with Grignard reagent （1.3 mmol） mediated by NiCl2 （4 mol%） and （p-CH3Ph）3P （8 mol%） in THF could produce 1,2-disubstituted acetylenes in good yields at room temperature.     

Nickel-catalyzed cross-coupling between functionalized primary or secondary alkylzinc halides and primary alkyl halides.

In the presence of Bu(4)NI (3 equiv) and 4-fluorostyrene (20 mol %), unreactive primary and secondary alkylzinc iodides undergo nickel-catalyzed cross-couplings with various primary alkyl iodides or bromides. More reactive secondary dialkylzincs and the mixed zinc organometallics RZnTMSM undergo the cross-coupling reaction in the absence of Bu(4)NI. The bicyclic secondary diorganozinc 6 prepared via boron-zinc exchange reacts with high retention of configuration. Free NH-groups are tolerated in the cross-coupling allowing the synthesis of aminated products.     

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.     

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.     

Nickel-catalyzed cross-coupling of unactivated alkyl halides and tosylate carrying a functional group with alkyl and phenyl Grignard reagents

By the use of catalytic amounts of a nickel salt and a 1,3-butadiene, primary and secondary alkyl Grignard reagents undergo cross-coupling with alkyl bromides, iodide, and tosylate carrying a functional group such as amide, ester, and ketone at 0 °C in THF. The present procedure provides a simple, convenient, and practical method for construction of carbon chains in the presence of various functional groups. PhMgBr also gave the corresponding coupling product in a moderate yield.     

An unprecedented iron-catalyzed cross-coupling of primary and secondary alkyl Grignard reagents with non-activated aryl chlorides

The use of N-heterocyclic carbene ligands in the iron-catalyzed cross-coupling of alkyl Grignards has allowed, for the first time, coupling of non-activated, electron rich aryl chlorides. Surprisingly, the tetrahydrate of FeCl₂ was found to be a better pre-catalyst than anhydrous FeCl₂. Primary Grignard reagents coupled in excellent yields while secondary Grignard reagents coupled in modest yields. The use of acyclic secondary Grignard reagents resulted in the formation of isomers in addition to the desired product. These isomeric products were formed via reversible β-hydrogen elimination, indicating that the cross-coupling proceeds through an ionic pathway.     

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.     

Nickel-catalyzed cross-coupling of potassium aryl- and heteroaryltrifluoroborates with unactivated alkyl halides

A method for the cross-coupling of alkyl electrophiles with various potassium aryl- and heteroaryltrifluoroborates has been developed. Nearly stoichiometric amounts of organoboron species could be employed to cross-couple a large variety of challenging heteroaryl nucleophiles. Several functional groups were tolerated on both the electrophilic and the nucleophilic partners. Chemoselective reactivity of C(sp(3))-Br bonds in the presence of C(sp(2))-Br bonds was achieved.     

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.     

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.     

Cobalt- and rhodium-catalyzed cross-coupling reaction of allylic ethers and halides with organometallic reagents

Reactions of 2-alkenyl methyl ether with phenyl, trimethylsilylmethyl, and allyl Grignard reagents in the presence of cobalt(II) complexes are discussed. The success of the reactions heavily depends on the combination of the substrate, ligand, and Grignard reagent. In the reaction of cinnamyl methyl ether, the formation of the linear coupling products predominates over that of the relevant branched products. In the cobalt-catalyzed allylation of allylic ethers, addition of a diphosphine ligand can change the regioselectivity, mainly providing the corresponding branched products. Rhodium complexes catalyze the reactions of allylic ethers and halides with allylmagnesium chloride and allylzinc bromide, respectively, in which the branched coupling product is the major product.     

Nickel-catalyzed N-heterocycle-directed cross-coupling of fluorinated arenes with organozinc reagents

Nickel-catalyzed N-heteroaromatics, such as pyridine, pyrazine or pyrimidine-directed cross-coupling of fluorinated arenes with organozinc reagents in the presence of sodium and PCy₃ was reported.     

Copper-catalyzed cross-coupling of nonactivated secondary alkyl halides and tosylates with secondary alkyl Grignard reagents

Practical catalytic cross-coupling of secondary alkyl electrophiles with secondary alkyl nucleophiles under Cu catalysis has been realized. The use of TMEDA and LiOMe is critical for the success of the reaction. This cross-coupling reaction occurs via an S(N)2 mechanism with inversion of configuration and therefore provides a general approach for the stereocontrolled formation of C-C bonds between two tertiary carbons from chiral secondary alcohols.     

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.     

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.     

Copper-mediated cross-coupling of functionalized arylmagnesium reagents with functionalized alkyl and benzylic halides

[reaction: see text]. Functionalized arylmagnesium halides, prepared via an iodine-magnesium exchange, undergo a smooth cross-coupling reaction with functionalized primary alkyl iodides and benzylic bromides in the presence of CuCN.2LiCl, either in stoichiometric (with trimethyl phosphite as an additive) or catalytic quantities.     

Preparation of unsymmetrical terphenyls via the nickel-catalyzed cross-coupling of alkyl biphenylsulfonates with aryl Grignard reagents

Unsymmetrical terphenyl derivatives were prepared by sequential transition metal-catalyzed cross-coupling reactions of neopentyl bromobenzenesulfonates with arylboronic acids and arylmagnesium bromides in good yields. Biphenylsulfonates undergo nickel-catalyzed coupling reactions more rapidly than the corresponding benzenesulfonates. The stepwise palladium- and nickel-catalyzed reaction of the bromobenzenesulfonates appears to be a promising and conceptually straightforward route for preparing unsymmetrical terphenyls.