Nickel-Catalyzed Cross-Electrophile Coupling Research Articles

Nickel-Catalyzed Cross-Electrophile Coupling of Vinyl Acetates and Alkyl Bromides

Nickel-Catalyzed Cross-Electrophile Coupling of Vinyl Acetates and Alkyl Bromides

Nickel-Catalyzed Reductive Cross-Coupling of Oxalates Derived from α-Hydroxy Carbonyls with Vinyl Bromides

AbstractA nickel-catalyzed cross-electrophile coupling is disclosed in which a range of vinyl bromides were utilized as electrophiles with oxalates derived from α-hydroxy carbonyls as precursors to carbonyl radical coupling partners. This method is compatible with a broad range of functional groups, providing a complementary solution for the construction of β,γ-unsaturated carbonyl compounds.

Nickel-Catalyzed Reductive Cross-Coupling of Benzylic Sulfonium Salts with Aryl Iodides

A nickel-catalyzed cross-electrophile coupling of benzylic sulfonium salts with aryl iodides has been developed, providing direct access to diarylalkanes from readily available and stable coupling partners. Preliminary mechanistic studies suggest that the C–S bond cleavage proceeds through a single-electron transfer process to generate a benzylic radical.

Unlocking the Friedel-Crafts arylation of primary aliphatic alcohols and epoxides driven by hexafluoroisopropanol

Unlocking the Friedel-Crafts arylation of primary aliphatic alcohols and epoxides driven by hexafluoroisopropanol

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

Synthesis of Multisubstituted Allenes via Nickel-Catalyzed Cross-Electrophile Coupling

Synthesis of Multisubstituted Allenes via Nickel-Catalyzed Cross-Electrophile Coupling

Nickel-Catalyzed Reductive Cross-Coupling of Heteroaryl Chlorides and Aryl Chlorides

We report a nickel-catalyzed cross-electrophile coupling reaction of aryl chlorides and heteroaryl chlorides enabled by a synergistic combination consisting of halide effects and the addition of a magnesium salt. The reaction relies on the electronic difference between the aromatic and heteroaromatic coupling partners to afford the cross-coupled biaryl products using a single catalyst. A variety of heterocycles were amenable to the reaction, as well as a wide range of aryl chlorides, with electron-deficient aryl chlorides performing the best in the reaction. Preliminary mechanistic evidence demonstrates the MgCl2 is essential to the reaction by accelerating the reduction of Ni(II), and that small quantities of iodide lead to improved yields.

A Ball-Milling-Enabled Cross-Electrophile Coupling.

The nickel-catalyzed cross-electrophile coupling of aryl halides and alkyl halides enabled by ball-milling is herein described. Under a mechanochemical manifold, the reductive C-C bond formation was achieved in the absence of bulk solvent and air/moisture sensitive setups, in reaction times of 2 h. The mechanical action provided by ball milling permits the use of a range of zinc sources to turnover the nickel catalytic cycle, enabling the synthesis of 28 cross-electrophile coupled products.

Nickel-Catalyzed Cross-Electrophile Coupling Enabled by Photoinduced Fragmentation of an EDA Complex

Nickel-Catalyzed Cross-Electrophile Coupling Enabled by Photoinduced Fragmentation of an EDA Complex

Nickel-Catalyzed Cross-Electrophile Coupling between C(sp2)–F and C(sp2)–Cl Bonds by the Reaction of ortho-Fluoro-Aromatic Amides with Aryl Chlorides

Ni-catalyzed cross-electrophile coupling between C(sp2)–F bonds in ortho-fluoro-substituted aromatic amides and C(sp2)–Cl bonds in aryl chlorides in the presence of Zn as a reductant and LiOtBu as ...

(-)-Isoscopariusin A, a Naturally Occurring Immunosuppressive Meroditerpenoid: Structure Elucidation and Scalable Chemical Synthesis.

(-)-Isoscopariusin A was isolated from the aerial parts of Isodon scoparius. Chemical synthesis and spectroscopic analysis established its structure as an unsymmetrical meroditerpenoid bearing a sterically congested 6/6/4 tricyclic carbon skeleton with seven continuous stereocenters. A gram-scale synthesis was achieved in 12 steps from commercially available (+)-sclareolide. A cobalt catalyzed, hydrogen atom transfer-based olefin isomerization was used to prepare a trisubstituted alkene, which underwent stereoselective [2+2] cycloaddition with a substituted keteniminium ion generated in situ from the corresponding amide. The cyclobutanone product was further elaborated into the fully substituted cyclobutane core through face-selective homologation, and the two side chains were installed by using nickel-catalyzed cross-electrophile coupling and carbodiimide-mediated esterification, respectively. (-)-Isoscopariusin A displayed selective inhibition of T-cell proliferation.

Nickel-Catalyzed Cross-Electrophile Coupling of the Difluoromethyl Group for Fluorinated Cyclopropane Synthesis

AbstractHerein, we report a new strategy for fluorinated cyclopropane synthesis. Photocatalytic olefin difluoromethylation is coupled with a nickel-catalyzed intramolecular cross-electrophile coupling (XEC) reaction between a difluoromethyl moiety and a benzylic ether. To the best of our knowledge, this is the first example of a XEC reaction employing a difluoromethyl group as an electrophile. A plausible mechanism is highlighted, and DFT calculations are included to support the observed stereochemical outcome.

Nickel-catalyzed cross-electrophile coupling of aryl bromides and cyclic secondary alkyl bromides with spiro-bidentate-pyox ligands

The cross-electrophile coupling catalyzed by nickel/spiro-bidentate-pyox ligands with lithium chloride as the additive was reported, which has good functional group tolerance (19 examples).

Nickel-catalyzed cross-electrophile coupling of aryl chlorides with allylic alcohols.

Nickel-catalyzed cross-electrophile coupling of aryl chlorides with allylic alcohols proceeds readily under mild conditions in the presence of zinc powder and MgCl2 to produce allylarenes in 25-92% yields. The reaction shows high regioselectivity and E/Z-selectivity, giving linear allylation products with an E configurated double bond when 1- or 3-arylallyl alcohols were used as the substrates. Functional groups including F, CF3, COOEt, NMe2, OMe, SiMe3, OH and vinyl groups as well as nitrogen-containing heterocycles were tolerated.

Nickel-Catalyzed Cross-Electrophile Coupling Reactions for the Synthesis of gem-Difluorovinyl Arenes

A nickel-catalyzed cross-electrophile coupling reaction between (hetero)aryl bromides and 2,2-difluorovinyl tosylate is presented. This protocol provides facile incorporation of the gem-difluorovinyl moiety in organic molecules. The method features mild reaction conditions, good functional group tolerance, and excellent yields. Furthermore, mechanistic experiments and DFT studies indicate a Ni(0)/Ni(II) catalytic cycle, thus differing from the currently accepted catalytic cycle for nickel-catalyzed C(sp2)–C(sp2) cross-electrophile coupling reactions.

Nickel-Catalyzed Cross-Electrophile Coupling of Aryl Chlorides with Primary Alkyl Chlorides.

Alkyl chlorides and aryl chlorides are among the most abundant and stable carbon electrophiles. Although their coupling with carbon nucleophiles is well developed, the cross-electrophile coupling of aryl chlorides with alkyl chlorides has remained a challenge. We report here the first general approach to this transformation. The key to productive, selective cross-coupling is the use of a small amount of iodide or bromide along with a recently reported ligand, pyridine-2,6-bis(N-cyanocarboxamidine) (PyBCamCN). The scope of the reaction is demonstrated with 35 examples (63 ± 16% average yield), and we show that the Br- and I- additives act as cocatalysts, generating a low, steady-state concentration of more-reactive alkyl bromide/iodide.

Enantioselective Three-Component Fluoroalkylarylation of Unactivated Olefins through Nickel-Catalyzed Cross-Electrophile Coupling.

A nickel-catalyzed, enantioselective, three-component fluoroalkylarylation of unactivated alkenes with aryl halides and perfluoroalkyl iodides has been described. This cross-electrophile coupling protocol utilizes a chiral nickel/BiOx system as well as a pendant chelating group to facilitate the challenging three-component, asymmetric difunctionalization of unactivated alkenes, providing direct access to valuable chiral β-fluoroalkyl arylalkanes with high efficiency and excellent enantioselectivity. The mild conditions allow for a broad substrate scope as well as good functional group toleration.

Nickel-Catalyzed Chain-Walking Cross-Electrophile Coupling of Alkyl and Aryl Halides and Olefin Hydroarylation Enabled by Electrochemical Reduction.

The first electrochemical approach for nickel-catalyzed cross-electrophile coupling was developed. This method provides a novel route to 1,1-diarylalkane derivatives from simple and readily available alkyl and aryl halides in good yields and excellent regioselectivity under mild conditions. The procedure shows good tolerance for a broad variety of functional groups and both primary and secondary alkyl halides can be used. Furthermore, the reaction was successfully scaled up to the multigram scale, thus indicating potential for industrial application. Mechanistic investigation suggested the formation of a nickel hydride in the electroreductive chain-walking arylation, which led to the development of a new nickel-catalyzed hydroarylation of styrenes to provide a series of 1,1-diaryl alkanes in good yields under mild reaction conditions.

Nickel-Catalyzed Alkyl-Alkyl Cross-Electrophile Coupling Reaction of 1,3-Dimesylates for the Synthesis of Alkylcyclopropanes.

Cross-electrophile coupling reactions of two Csp3-X bonds remain challenging. Herein we report an intramolecular nickel-catalyzed cross-electrophile coupling reaction of 1,3-diol derivatives. Notably, this transformation is utilized to synthesize a range of mono- and 1,2-disubstituted alkylcyclopropanes, including those derived from terpenes, steroids, and aldol products. Additionally, enantioenriched cyclopropanes are synthesized from the products of proline-catalyzed and Evans aldol reactions. A procedure for direct transformation of 1,3-diols to cyclopropanes is also described. Calculations and experimental data are consistent with a nickel-catalyzed mechanism that begins with stereoablative oxidative addition at the secondary center.

Nickel catalyzed deoxygenative cross-coupling of benzyl alcohols with aryl-bromides

A nickel-catalyzed cross-electrophile coupling of benzyl alcohols with aromatic bromides has been developed. This deoxygenative cross-coupling occurs under mild reaction conditions at ambient temperature affording diarylmethanes, or 1,3-diarylpropenes from benzyl allyl alcohols. The system demonstrated good chemoselectivity tolerating an assortment of reactive functional groups.