Nickel-catalyzed reductive cyclizations and couplings

For over 50 years, nickel catalysis has been applied in cycloaddition processes. Nickel-catalyzed reductive couplings and cyclizations, however, have only recently attracted a high level of interest. This group of new reactions allows a broad range of multicomponent couplings involving two or more pi components with a main-group or transition-metal reagent. These processes allow the assembly of important organic substructures from widely available reaction components. Multiple contiguous stereocenters, polycyclic ring systems, and novel arrays of complex functionality may often be prepared from simple, achiral, acyclic precursors. With three or more reactive functional groups participating in the catalytic processes, many mechanistic questions abound, including the precise timing of bond constructions and the nature of reactive intermediates. This Review is thus aimed at providing a critical evaluation of recent progress in this rapidly developing field.     

Nickel-catalyzed couplings and cyclizations involving allenes, aldehydes, and organozincs

Cyclizations of allenyl aldehydes and intermolecular couplings of allenes and aldehydes provide a direct procedure for the preparation of homoallylic alcohols. The couplings and cyclizations involve the use of diorganozinc reagents as reducing agents and Ni(COD)₂ as the catalyst.     

Nickel-catalyzed carboxylation of organozinc reagents with CO2

An efficient nickel catalyst system for the carboxylation of organozinc reagents with CO(2) under very mild conditions has been developed. The catalyst system complements the conventional methods and enables the direct synthesis of various saturated carboxylic acid derivatives from the corresponding alkylzinc reagents and CO(2).     

Cascade cyclizations and couplings involving nickel enolates

A new strategy for effecting cascade cyclization processes using nickel enolates has been developed. Nickel enolates may be cleanly generated by the oxidative cyclization of an enal and alkyne with Ni(0), and the resulting enolate may be functionalized by a variety of alkylation processes. Partially and fully intramolecular versions of the process allow the rapid synthesis of complex polycyclics from simple achiral, acyclic precursors.     

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 monosubstitution of polyfluoroarenes with organozinc reagents using alkoxydiphosphine ligand

A new diphosphine (POP) ligand bearing an alkoxide group allows us to synthesize partially fluorinated arenes. A nickel-catalyzed cross-coupling between a polyfluoroarene and an organozinc reagent in the presence of POP selectively produces a monosubstitution product. Aryl and alkylzinc reagents smoothly take part in the reaction. It is speculated that monosubstitution is the result of accelerated product expulsion from the product/catalyst complex.     

Nickel-catalyzed cross-coupling of primary alkyl halides with phenylethynyl- and trimethylsilyethynyllithium reagents

A highly efficient alkyl-alkynyl coupling system is described which is promoted by a well-defined and moisture-stable pincer complex [NiCl{C₆H₃-2,6-(OPPh₂)₂}] (1). Non-activated alkyl halides could be efficiently coupled with phenylethynyl- and trimethylsilylethynyllithium reagents at room temperature. Compared to the alkylation of primary alkyl halides with alkynyllithium reagents in literatures, this method requires milder conditions (room temperature) and proceeds quickly. This research will make these readily available alkynyllithium reagents much more useful for organic synthesis.     

Nickel-catalyzed cross-couplings of organosilicon reagents with unactivated secondary alkyl bromides

A metal-catalyzed cross-coupling of organosilicon compounds with alkyl halides has been developed. Noteworthy attributes of the method are its scope (secondary electrophiles), its high functional-group compatibility, and the air stability of the catalyst components.     

Nickel-catalyzed asymmetric cross-couplings of racemic propargylic halides with arylzinc reagents

A stereoconvergent method for the catalytic asymmetric Negishi cross-coupling of racemic secondary propargylic halides with arylzinc reagents has been developed. Neither family of compounds has previously been shown to be a suitable partner in such coupling processes. From a practical point of view, it is noteworthy that the catalyst components (NiCl2.glyme and pybox ligand 1) are commercially available.     

Nickel-catalyzed electrochemical couplings of vinyl halides: synthetic and stereochemical aspects

Homo- and cross-coupling involving alkenyl halides have been performed efficiently using an electroassisted nickel-complex catalysis. Valuable product such as conjugated dienes, beta,gamma- or gamma,delta-unsaturated esters, ketones, or nitriles, as well as alkenylated aryl compounds are thus prepared with high yields and high stereoselectivity. Partial isomerization is only observed in a few cases, when the alkenyl halide is involved in a late step of the catalytic cycle. This is the case in the preparation of (Z,Z)-1,3-diene.     

Nickel-catalyzed carbometallation of functionalized silylalkynes by grignard reagents

Syntheses of vinylsilanes by the nickel catalyzed addition of methyl-magnesium bromide to functionalized silylalkynes are described. Simple syntheses of geraniol and farnesol are reported.     

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.     

Diastereoselective cobalt-catalyzed alkylative aldol cyclizations using trialkylaluminum reagents

Co(acac)2.2H2O serves as an effective precatalyst for alkylative aldol cyclizations of alpha,beta-unsaturated amides with ketones using trialkylaluminum reagents. These reactions provide beta-hydroxylactams containing three contiguous stereocenters with high levels of diastereoselection.     

Nickel-catalyzed cross-coupling reactions of benzylic zinc reagents with aromatic bromides, chlorides and tosylates

Benzylic zinc reagents prepared by direct insertion of zinc to benzylic chlorides in the presence of LiCl undergo smooth cross-coupling reactions with aromatic chlorides, bromides and tosylates using Ni(acac)(2) and PPh(3) as a catalyst system.     

New catalytic cycle for couplings of aldehydes with organochromium reagents

[reaction: see text] A new catalytic cycle has been developed to effect all three subgroups of Cr-mediated couplings, i.e., (1) Ni/Cr-mediated alkenylation, alkynylation, and arylation, (2) Co/Cr-mediated 2-haloallylation, alkylation, and propargylation, and (3) Cr-mediated allylation. In the presence of chiral sulfonamide ligands, good asymmetric inductions can be achieved for some of the Ni/Cr-mediated alkenylation, Co/Cr-mediated 2-haloallylation and propargylation, and Cr-mediated allylation.