Manganese-catalyzed cross-coupling reaction between aryl Grignard reagents and alkenyl halides

Aryl Grignard reagents react stereospecifically with alkenyl halides in the presence of manganese chloride (10%) to afford good yields of cross-coupling products.     

Kinetic resolution of racemic Grignard reagents by nickel-catalyzed asymmetric Grignard cross-coupling

Racemic Grignard reagents, 2-phenylpropylmagnesium chloride and 2-norbornylmagnesium chloride were kinetically resolved by asymmetric cross-coupling with vinyl bromides in the presence of chiral phosphine-nickel catalysts to give optically active coupling products (~37% ee) and carboxylic acids after carbonation with carbon dioxide.     

Ligand exchange as the first irreversible step in the nickel-catalyzed cross-coupling reaction of Grignard reagents

Mechanistic studies of the Ni-catalyzed cross-coupling reaction of Grignard reagents through analysis of kinetic isotope effects and theoretical calculations indicated that the product-to-substrate ligand exchange process is the first irreversible step and affects the turnover efficiency and selectivity of the reaction. On the other hand, the oxidative addition step is the first irreversible step in Pd catalysis. This finding has useful implications for the development of efficient Ni catalysis and also illustrates the importance of the catalyst turnover step that has so far received less attention than subsequent catalytic steps.     

Traceless directing group for stereospecific nickel-catalyzed alkyl-alkyl cross-coupling reactions

Stereospecific nickel-catalyzed cross-coupling reactions of benzylic 2-methoxyethyl ethers are reported for the preparation of enantioenriched 1,1-diarylethanes. The 2-methoxyethyl ether serves as a traceless directing group that accelerates cross-coupling. Chelation of magnesium ions is proposed to activate the benzylic C-O bond for oxidative addition.     

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.     

Stereochemistry of transmetalation of alkylboranes in nickel-catalyzed alkyl-alkyl cross-coupling reactions

Deuterium-labeled alkylborane reagents 2a and 2b were prepared and subjected to cross-coupling reactions in the presence of a nickel catalyst. NMR analysis of the products indicates that transmetalation from boron to nickel proceeds with retention of configuration. These results demonstrate that alkylnickel intermediates are configurationally stable under Suzuki cross-coupling conditions.     

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.     

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-catalyzed cross-coupling reactions of alkyl halides with allylic and benzylic Grignard reagents and their application to tandem radical cyclization/cross-coupling reactions

Details of cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic Grignard reagents are disclosed. A combination of cobalt(II) chloride and 1,2-bis(diphenylphosphino)ethane (DPPE) or 1,3-bis(diphenylphosphino)propane (DPPP) is suitable as a precatalyst and allows secondary and tertiary alkyl halides--as well as primary ones--to be employed as coupling partners for allyl Grignard reagents. The reaction offers a facile synthesis of quaternary carbon centers, which has practically never been possible with palladium, nickel, and copper catalysts. Benzyl, methallyl, and crotyl Grignard reagents can all couple with alkyl halides. The benzylation definitely requires DPPE or DPPP as a ligand. The reaction mechanism should include the generation of an alkyl radical from the parent alkyl halide. The mechanism can be interpreted in terms of a tandem radical cyclization/cross-coupling reaction. In addition, serendipitous tandem radical cyclization/cyclopropanation/carbonyl allylation of 5-alkoxy-6-halo-4-oxa-1-hexene derivatives is also described. The intermediacy of a carbon-centered radical results in the loss of the original stereochemistry of the parent alkyl halides, creating the potential for asymmetric cross-coupling of racemic alkyl halides.     

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.     

Iron-catalysed, hydride-mediated reductive cross-coupling of vinyl halides and Grignard reagents

An iron-catalysed, hydride-mediated reductive cross-coupling reaction has been developed for the preparation of alkanes. Using a bench-stable iron(II) pre-catalyst, reductive cross-coupling of vinyl iodides, bromides and chlorides with aryl- and alkyl Grignard reagents successfully gave the products of formal sp(3)-sp(3) cross-coupling reactions.     

Enantioselective nickel-catalyzed cross-coupling reactions of trialkynylindium reagents with racemic secondary benzyl bromides

The first enantioselective sp-sp3 cross-coupling reaction between alkynyl organometals and racemic benzyl bromides is reported. The coupling is performed at room temperature by using NiBr2diglyme and (S)-(iPr)-Pybox as the catalytic system and trialkynylindium reagents as nucleophiles. The reaction is stereoconvergent, both enantiomers of the racemic benzyl bromide are converted into one enantiomer of the product, and stereospecific. The reaction takes place efficiently in good yields and with high atom economy, as the triorganoindium reagents transfer the three organic groups attached to indium (only 40 mol % of R3In is used).     

Ni- or Cu-catalyzed cross-coupling reaction of alkyl fluorides with Grignard reagents

n-Octyl fluoride underwent a cross-coupling reaction with n-propylmagnesium bromide in the presence of 1,3-butadiene using NiCl2 as a catalyst at room temperature to give undecane in moderate yields. This alkyl-alkyl cross-coupling proceeded more efficiently when CuCl2 was employed instead of NiCl2. Addition of 1,3-butadiene dramatically improved the yields of the coupling products from primary alkyl Grignard reagents in both Ni- and Cu-catalyzed reactions. Alkyl fluorides efficiently reacted with tertiary alkyl and phenyl Grignard reagents using CuCl2 in the absence of 1,3-butadiene to afford the coupling products in high yields. The competitive reaction of a mixture of alkyl halides (R-X; X = F, Cl, Br) with nC5H11MgBr showed that the reactivities of the halides increase in the order R-Cl < R-F < R-Br. In contrast, in the Cu-catalyzed reaction with PhMgBr, the reactivities increase in the order R-Cl < R-Br < R-F.     

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.     

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.     

Iron-catalyzed cross-coupling of imidoyl chlorides with Grignard reagents

[reaction: see text] A general, high yielding rapid iron-catalyzed cross-coupling reaction between Grignard reagents and imidoyl chlorides is described. These reactions are typically completed within 5 min, resulting in high yields of 71-96% using 5% iron catalyst in a THF-NMP solvent mixture. Functionalized imidoyl chlorides (e.g., R = CO(2)Me) gave excellent yields (89%).