Oleg Vechorkin

Functional group tolerant Kumada-Corriu-Tamao coupling of nonactivated alkyl halides with aryl and heteroaryl nucleophiles: catalysis by a nickel pincer complex permits the coupling of functionalized Grignard reagents.

A nickel(II) pincer complex [((Me)NN(2))NiCl] (1) catalyzes Kumada-Corriu-Tamao cross coupling of nonactivated alkyl halides with aryl and heteroaryl Grignard reagents. The coupling of octyl bromide with phenylmagnesium chloride was used as a test reaction. Using 3 mol % of 1 as the precatalyst and THF as the solvent, and in the presence of a catalytic amount of TMEDA, the coupling product was obtained in a high yield. The reaction conditions could be applied to cross coupling of other primary and secondary alkyl bromides and iodides. The coupling is tolerant to a wide range of functional groups. Therefore, alkyl halides containing ester, amide, ether, thioether, alcohol, pyrrole, indole, furan, nitrile, conjugated enone, and aryl halide moieties were coupled to give high isolated yields of products in which these units stay intact. For the coupling of ester-containing substrates, O-TMEDA is a better additive than TMEDA. The reaction protocol proves to be efficient for the coupling of Knochel-type functionalized Grignard reagents. Thus aryl Grignard reagents containing electron-deficient and/or sensitive ester, nitrile, amide, and CF(3) substituents could be successfully coupled to nonactivated and functionalized alkyl iodides. The catalysis is also efficient for the coupling of alkyl iodides with functionalized heteroaryl Grignard reagents, giving rise to pyridine-, thiophene-, pyrazole-, furan-containing molecules with additional functionalities. Concerning the mechanism of the catalysis, [((Me)NN(2))Ni-(hetero)Ar] was identified as an intermediate, and the activation of alkyl halides was found to take place through a radical-rebound process.

Ni-Catalyzed Sonogashira Coupling of Nonactivated Alkyl Halides: Orthogonal Functionalization of Alkyl Iodides, Bromides, and Chlorides

Ni-catalyzed Sonogashira coupling of nonactivated, beta-H-containing alkyl halides, including chlorides, is reported. The coupling is tolerant to a wide range of functional groups, including ether, ester, amide, nitrile, keto, heterocycle, acetal, and aryl halide, in both coupling partners. The coupling can be selective for a specific C-X bond (X = I, Br, Cl) and allows for orthogonal functionalization of alkyl halides with multiple reactive sites.

Nickel Complexes of a Pincer NN2 Ligand: Multiple Carbon−Chloride Activation of CH2Cl2 and CHCl3 Leads to Selective Carbon−Carbon Bond Formation

A new pincer-type bis(amino)amine (NN2) ligand and its lithium and nickel complexes, including Ni(II) methyl, ethyl, and phenyl complexes, were synthesized. The Ni(II) alkyl complexes react cleanly with alkyl halides including chlorides to form C-C coupled products and Ni(II) halides. More interestingly, the Ni(II) alkyls undergo unprecedented reactions with CH2Cl2 and CHCl3 to cleave all the C-Cl bonds and replace them with C-C bonds. The reactions are highly selective and lead to the first efficient catalytic coupling of CH2Cl2 with alkyl Grignards. A conversion of 82% and a turnover number of 47 are achieved within minutes. Coupling of CD2Cl2 and 1,1-dichloro-3,3-dimethylbutane with nBuMgCl is also realized. Preliminary mechanistic study suggests a radical initiated process for these reactions.

The Nickel/Copper-Catalyzed Direct Alkylation of Heterocyclic CH Bonds†

A general and straightforward protocol for the cross-coupling of non-activated alkyl halides with heterocyclic CH bonds has been developed. The transformation is chemo- and regioselective and many functional groups on both coupling partners are tolerated. The method employs cheap nickel/copper catalysts, and expands significantly the scope of CH functionalization.

Carbon Dioxide as the C1 Source for Direct C−H Functionalization of Aromatic Heterocycles

A simple and straightforward method has been developed for the direct carboxylation of aromatic heterocycles such as oxazoles, thiazoles, and oxadiazoles using CO(2) as the C1 source. The reactions require no metal catalyst and only Cs(2)CO(3) as the base. A good functional group tolerance is achieved.

A Structure–Activity Study of Ni-Catalyzed Alkyl–Alkyl Kumada Coupling. Improved Catalysts for Coupling of Secondary Alkyl Halides

A structure-activity study was carried out for Ni catalyzed alkyl-alkyl Kumada-type cross coupling reactions. A series of new nickel(II) complexes including those with tridentate pincer bis(amino)amide ligands ((R)N(2)N) and those with bidentate mixed amino-amide ligands ((R)NN) were synthesized and structurally characterized. The coordination geometries of these complexes range from square planar, tetrahedral, to square pyramidal. The complexes had been examined as precatalysts for cross coupling of nonactivated alkyl halides, particularly secondary alkyl iodides, with alkyl Grignard reagents. Comparison was made to the results obtained with the previously reported Ni pincer complex [((Me)N(2)N)NiCl]. A transmetalation site in the precatalysts is necessary for the catalysis. The coordination geometries and spin-states of the precatalysts have a small or no influence. The work led to the discovery of several well-defined Ni catalysts that are significantly more active and efficient than the pincer complex [((Me)N(2)N)NiCl] for the coupling of secondary alkyl halides. The best two catalysts are [((H)NN)Ni(PPh(3))Cl] and [((H)NN)Ni(2,4-lutidine)Cl]. The improved activity and efficiency was attributed to the fact that phosphine and lutidine ligands in these complexes can dissociate from the Ni center during catalysis. The activation of alkyl halides was shown to proceed via a radical mechanism.

Nickel Complexes of a Pincer Amidobis(amine) Ligand: Synthesis, Structure, and Activity in Stoichiometric and Catalytic C—C Bond Forming Reactions of Alkyl Halides

The synthesis, properties, and reactivity of nickel(II) complexes of a newly developed pincer amidobis(amine) ligand ((Me)NN(2)) are described. Neutral or cationic complexes [((Me)NN(2))NiX] (X = OTf (6), OC(O)CH(3) (7), CH(3)CN (8), OMe (9)) were prepared by salt metathesis or chloride abstraction from the previously reported [((Me)NN(2))NiCl] (1). The Lewis acidity of the {((Me)NN(2))Ni} fragment was measured by the (1)H NMR chemical shift of the coordinated CH(3)CN molecule in 8. Electrochemical measurements on 1 and 8 indicate that the electron-donating properties of NN(2) are similar to those of the analogous amidobis(phosphine) (pnp) ligands. The solid-state structures of 6-8 were determined and compared to those of 1 and [((Me)NN(2))NiEt] (3). In all complexes, the (Me)NN(2) ligand coordinates to the Ni(II) ion in a mer fashion, and the square-planar coordination sphere of the metal is completed by an additional donor. The coordination chemistry of (Me)NN(2) thus resembles that of other three-dentate pincer ligands, for example, pnp and arylbis(amine) (ncn). Reactions of 2 with alkyl monohalides, dichlorides, and trichlorides were investigated. Selective C-C bond formation was observed in many cases. Based on these reactions, efficient Kumada-Corriu-Tamao coupling of unactivated alkyl halides and alkyl Grignard reagents with 1 as the precatalyst was developed. Good yields were obtained for the coupling of primary and secondary iodides and bromides. Double C-C coupling of CH(2)Cl(2) with alkyl Grignard reagents by 1 was also realized. The scope and limitations of these transformations were studied. Evidence was found for a radical pathway in Ni-catalyzed C-C cross-coupling reactions, which involves Ni(II) alkyl intermediates.

Cross-Coupling of Nonactivated Alkyl Halides with Alkynyl Grignard Reagents: A Nickel Pincer Complex as the Catalyst†

The nickel pincer complex 1 catalyzes the cross-coupling of the title compounds with remarkable substrate scope and functional group tolerance. A nickel/alkynyl species was isolated and shown to be catalytically competent. THF=tetrahydrofuran, O-TMEDA=bis[2-(N,N-dimethylaminoethyl)] ether.