Nickel-catalyzed Three-component Coupling Research Articles

Synthesis of gem-Difluorinated 1,4-Dienes via Nickel-Catalyzed Three-Component Coupling of (Trifluoromethyl)alkenes, Alkynes, and Organoboronic Acids.

Herein, a nickel-catalyzed defluorinative three-component coupling of trifluoromethyl alkenes, internal alkynes, and organoboronic acids is presented. The protocol provides a highly efficient and selective route for the synthesis of structurally diverse gem-difluorinated 1,4-dienes under mild conditions. Mechanistic studies suggest that C-F bond activation proceeds probably through the oxidative cyclization of trifluoromethyl alkenes with Ni(0) species, sequential addition to alkynes, and β-fluorine elimination.

Direct and modular access to allylic amines via nickel-catalyzed three-component coupling

We herein report direct and modular access to allylic amines via Ni(0)-catalyzed three-component coupling of commercially available and inexpensive aldehydes, amines, and alkenes, without the additional steps for isolation of unstable imines.

DFT calculations rationalize regioselectivity and chemodivergence in nickel-catalyzed couplings of aldehyde, alkyne, and dialkylsilane/trialkylsilane

DFT calculations were performed to understand the regioselectivity and chemodivergence in the nickel-catalyzed three-component coupling of aldehyde, alkyne, and dialkylsilane/trialkylsilane to synthesize silylated allylic alcohols and silacyclopentenes. The calculated results proposed a new mechanism for the formation of silacyclopentenes, rationalized the observed regioselectivity and chemodivergence, and identified the both the regioselectivity-determining step and the rate-determining step.

Nickel-Catalyzed Three-Component Cross-Electrophile Coupling of 1,3-Dienes with Aldehydes and Aryl Bromides.

We herein report a Ni-catalyzed three-component cross-electrophile coupling of 1,3-dienes with aldehydes and aryl bromides using manganese metal as the reducing agent. This efficient protocol accomplishes dicarbofunctionalization of 1,3-dienes to synthesize diverse structural 1,4-disubstituted homoallylic alcohols by forming two new C-C bonds in one time. Mechanistic study suggests that an allyl-nickel(I) species is involved in the catalytic cycle.

Ni-Catalyzed Coupling of Butadiene, Aldimines, and Arylboronic Acids to Homoallylic Amines under Base-Free Conditions

Herein, we report a nickel-catalyzed three-component coupling of butadiene, aldimines, and arylboronic acids to form synthetically important homoallylic amines. The starting materials are stable an...

Nickel-Catalyzed Carboalkenylation of 1,3-Dienes with Aldehydes and Alkenylzirconium Reagents: Access to Skipped Dienes.

A regio- and stereoselective nickel-catalyzed three-component coupling reaction of aldehydes, 1,3-dienes, and alkenylzirconium reagents was realized. The ligand- and additive-free protocol afforded a convenient approach to the synthesis of skipped diene compounds bearing various functionals (e.g., hydroxyl, carbonyl, halide) and heterocyclic groups. The products were readily transformed into structurally diverse polyenes. The utility of this reaction was also demonstrated by the one-pot operation and scale-up preparation.

Ni(0)-Catalyzed Three-Component Coupling Reaction of Tetrafluoroethylene and N-Sulfonyl-Substituted Imines with Silanes via Aza-Nickelacycles.

A nickel-catalyzed three-component coupling reaction of tetrafluoroethylene (TFE) and N-sulfonyl-substituted imines with silanes that furnishes a variety of fluorine-containing amines is disclosed. Stoichiometric experiments revealed that the aza-nickelacycles generated upon oxidative cyclization of TFE and N-sulfonyl-substituted imines on Ni(0) were identified as the key intermediates in this catalytic reaction. A single-crystal X-ray diffraction analysis of such an aza-nickelacycle revealed that the O atom of the N-sulfonyl group stabilizes the key intermediate via coordination to the nickel center.

Ni-Catalyzed Dimerization and Hydroperfluoroarylation of 1,3-Dienes.

A nickel-catalyzed three-component coupling reaction between perfluoroarenes and two molecules of a 1,3-diene in the presence of an alkyl Grignard reagent, which acted as a hydride source, provided 3-perfluoroarylated-1,7-octadienes via 1,3-diene dimerization and subsequent perfluoroarylation upon C-F bond cleavage. The reaction proceeded smoothly in a regioselective manner by simply combining NiCl2 and PPh3 as a catalyst and tolerated various functional groups on the perfluoroarenes. When substituted perfluoroarenes were employed, the reaction selectively occurred at the para-position. Mechanistic studies revealed that an anionic Ni complex, generated upon the reaction of Ni(0) with two molecules of a 1,3-diene and an alkyl Grignard reagent, played an important role in the C-C bond forming step with perfluoroarenes. The C-F bond cleavage was found to be a relatively fast step in the catalytic cycle.

Mechanism for Three-Component Ni-Catalyzed Carbonyl–Ene Reaction for CO2 Transformation: What Practical Lessons Do We Learn from DFT Modelling?

In the present study, we use computational quantum chemistry to examine the nickel-catalyzed three-component coupling for transforming CO2 into a homoallylic alcohol. We find that the reaction is limited by several Ni-assisted atom transfer reactions in the catalytic cycle, in which a new product formation pathway is found from our calculations. Our results also point towards several key factors for an efficient reaction. Thus, substrates that would lead to a stabilized alkene facilitate a key step in the catalytic cycle. The optimal phosphine ligand should provide a good balance between directing stereochemistry with its steric bulk and enabling the reaction without being excessively bulky. Our calculations also highlight the importance of carefully chosen substrates and ligands in order to avoid potential side reactions, and that knowing the conformational preference in the substrate alone may not be sufficient for predicting the stereochemistry.

Mechanism and Origin of Et2Al(OEt)-Induced Chemoselectivity of Nickel-Catalyzed Three-Component Coupling of One Diketene and Two Alkynes

Density functional theory (DFT) calculations have been performed to unravel the mechanism of Lewis-acid-induced Ni(cod)2-catalyzed selective coupling reactions of one diketene and two alkynes. Complex mixtures (unsymmetrical phenylacetic acid P1, symmetrical phenylacetic acid P2 and (3E)-4-ethyl-5-methylene-3-heptenoic acid P3) were obtained in the absence of Et2Al(OEt). P1 formation involves C(sp2)-O oxidative addition of diketene, twice alkyne insertion, intramolecular C═C insertion, acidolysis, and β-H elimination. For P2/P3 formation, the common key issue related to the C═C double bond cleavage of the substrate diketene was explored and found that it was accomplished via a four-membered-ring-closure/four-membered-ring-opening process. And then, P2 was produced via the second alkyne insertion while P3 was accessed by a stoichiometric reaction with HCl. The Et2Al(OEt)-induced chemoselectivity was also probed. It is found that the Ni–O (from Al reagent) bonding facilitates the second alkyne insertion, an...

ChemInform Abstract: Chiral Ditopic Cyclophosphazane (CycloP) Ligands: Synthesis, Coordination Chemistry, and Application in Asymmetric Catalysis.

A series of dichlorocyclophosphazanes [{ClP(μ-NR)}2 ] containing chiral and achiral R groups was obtained from simple commercially available amines and PCl3 . Their condensation reactions with axially chiral biaryl diols yielded ansa-bridged chiral cyclophosphazane (CycloP) ligands. This highly modular methodology allows extensive elaboration of the ligand set, in which the chirality can be introduced at the diol bridge and/or the amido R group. This provides the possibility to observe match and mismatch effects in catalysis. A series of twenty CycloP ligands was synthesized and characterized by multinuclear NMR spectroscopy, HRMS, elemental analysis, and in selected cases, single-crystal X-ray diffraction. These studies show that all of the ditopic CycloP ligands are C2 symmetric, rendering their metal coordination sites symmetry equivalent. Two well-established enantioselective reactions were explored by using late-transition metal CycloP complexes as catalysts; the gold-catalyzed hydroamination of γ-allenyl sulfonamides and the asymmetric nickel-catalyzed three-component coupling of a diene and an aldehyde. The steric demands of the CycloP ligands have a subtle influence on the reactivity and selectivity observed in both reactions. Good enantiomeric ratios (e.r.) as high as 89:11 in the gold-catalyzed reaction and 92:8 in the nickel-catalyzed bis-homoallylation reaction were observed.

Nickel-Catalyzed Ligand-Free Systhesis of Benzoxazoles and Oxazolines via Isocyanide Insertion

An efficient route for the synthesis of the title compounds via nickel-catalyzed three-component coupling reaction of various iodobenzenes, an amino alcohol, and tert-butylisocyanide is given.

Nickel-Catalyzed Ring-Opening Three-Component Coupling of Methylenecyclopropane with Aldehydes and Silanes

A nickel-catalyzed three-component coupling between methylenecyclopropane, aldehydes, and silanes afforded silylated allylic alcohols that possess an alkyl substituent at the 2-position via cleavage of the proximal C-C bond of methylenecyclopropane.

Highly Selective Nickel-Catalyzed Three-Component Coupling of Alkynes with Enones and Alkenyl Boronic Acids: A Novel Route to Substituted 1,3-Dienes

A highly regio- and stereoselective nickel-catalyzed three-component coupling of alkynes with enones and alkenyl boronic acids to afford highly substituted 1,3-dienes is described. The reaction can also be extended to cyclization of enynes with coupling to alkenyl boronic acids. A possible reaction mechanism involving a five-membered nickelacycle as a key intermediate is proposed.

Asymmetric Synthesis of γ-Siloxyenamides via Chiral Auxiliary-Mediated Diastereoselective Coupling of Ynamides, Aldehydes, and Silane by Nickel Catalyst

The nickel-catalyzed three-component coupling of optically active oxazolidinone-derived ynamides (I) and (V), aldehydes, and silane (III) proceeds via oxanickelacycle to afford γ-siloxyenamides (IV), (VI), and (VIII) in a regio- and stereoselective manner.

Diastereoselective Coupling of 1,3-Diene, Ketone, and Organometallic Reagents by Nickel Catalyst: Stereoselective Construction of Tetrasubstituted Carbon Centers

Abstract A nickel-catalyzed three-component coupling of 1,3-diene, ketone, and organoboron or organosilicon reagents was investigated. While the coupling reaction using PhB(OH)2 afforded a 1,3-syn-substituted 4-penten-1-ol derivative as a single diastereomer, the reaction in the presence of tetraorganosilicon reagent under similar conditions exclusively produced the corresponding 1,3-anti isomer. In both reactions, a tetrasubstituted carbon center was constructed in a highly diastereoselective manner.

Nickel-Catalyzed Enantioselective Three-Component Coupling of Bis-1,3-dienes, Aldehydes, and Dimethylzinc

Nickel-catalyzed three-component coupling of bis-1,3-dienes, aldehyde, and dimethylzinc was investigated. In the presence of catalytic amounts of Ni(acac)2 and PPh3, bis-1,3-dienes smoothly react with an aldehyde and dimethylzinc via intramolecular cyclodimerization of bis-1,3-diene moiety. The reaction proceeds through formation of a cyclic bis-allylnickel complex, insertion of an aldehyde, and addition of dimethylzinc to the resulting oxanickellacycle intermediate. An enantioselective coupling was also achieved by the use of a chiral monodentate phosphine ligand, H-MOP.