Transition-Metal-Mediated Cleavage and Activation of C–C Single Bonds

We report here that hydroxyphosphine ligands (PO ligands) significantly accelerate nickel-catalyzed cross-coupling reactions of unreactive aryl electrophiles and Grignard reagents. The new catalytic system based on the nickel-PO-Grignard combination allows facile activation of unreactive aryl halides such as fluorides, chlorides, polyfluorides, and polychlorides as well as phenol derivatives such as carbamates and phosphates to give the corresponding cross-coupling products in good to excellent yields. We ascribe the high catalytic activity to a nickel phosphine/magnesium alkoxide bimetallic species that forms from the nickel precatalyst, the PO ligand, and the Grignard reagent and undergoes activation of the aryl-X bond by a cooperative push-pull action of the nucleophilic nickel and Lewis acidic magnesium centers. This mechanistic conjecture was corroborated by kinetic isotope effect experiments and density functional theory calculations. Being distinct from the conventional three-centered mechanism for oxidative addition, the proposed mechanism for the C-X bond activation offers a new concept for the design of cross-coupling reactions as well as other homogeneous catalyses involving activation of electrophilic substrates.

Hydroxyphosphine Ligand for Nickel-Catalyzed Cross-Coupling through Nickel/Magnesium Bimetallic Cooperation

The enantioselective, intramolecular arylcyanation of unactivated olefins via C–CN bond activation has been accomplished using a Ni(0) catalyst and BPh3 co-catalyst. High enantioselectivities are achieved using TangPHOS as a chiral ligand. This method allows generation of two new C–C bonds and one new quaternary carbon stereogenic center in a single synthetic step, converting readily available benzonitrile substrates into 1,1-disubstituted indanes in 49–85% yield and 92–97% ee.

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Asymmetric Intramolecular Arylcyanation of Unactivated Olefins via C−CN Bond Activation

The mechanisms for Ni(dppe)Cl2-catalyzed chain-growth polymerization of 4-bromo-2,5-bis(hexyloxy)phenylmagnesium chloride and 5-bromo-4-hexylthiophen-2-ylmagnesium chloride were investigated. Rate studies utilizing IR spectroscopy and gas chromatography revealed that both polymerizations exhibit a first-order dependence on the catalyst concentration but a zeroth-order dependence on the monomer concentration. 31P NMR spectroscopic studies of the reactive organometallic intermediates suggest that the resting states are unsymmetrical NiII−biaryl and NiII−bithiophene complexes. In combination, the data implicate reductive elimination as the rate-determining step for both monomers. Additionally, LiCl was found to have no effect on the rate-determining step or molecular weight distribution in the arene polymerization.

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Mechanistic studies on Ni(dppe)Cl2-catalyzed chain-growth polymerizations: Evidence for rate-determining reductive elimination

Cyanoformates and cyanoformamides are found to add across alkynes by nickel/Lewis acid (LA) cooperative catalysis to give beta-cyano-substituted acrylates and acrylamides, respectively, in highly stereoselective and regioselective manners. The resulting adducts serve as versatile synthetic building blocks through chemoselective transformations of the ester, amide, and cyano groups as demonstrated by the synthesis of typical structures of beta-cyano ester, beta-amino nitrile, gamma-lactam, disubstituted maleic anhydride, and gamma-aminobutyric acid. The related reactions of cyanoformate thioester and benzoyl cyanide, on the other hand, are found to add across alkynes with decarbonylation in the presence of a palladium/LA catalyst.

Tülay A. Ateşin

Papers

Experimental and Theoretical Examination of C−CN Bond Activation of Benzonitrile Using Zerovalent Nickel