Nonactivated Alkyl Halides Research Articles

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.

Back Cover: Tuning Chemoselectivity in Iron‐Catalyzed Sonogashira‐Type Reactions Using a Bisphosphine Ligand with Peripheral Steric Bulk: Selective Alkynylation of Nonactivated Alkyl Halides (Angew. Chem. Int. Ed. 46/2011)

Iron complexes synthesized from iron salts and a newly developed bisphosphine ligand are described by M. Nakamura et al. in their Communication on page 10 973 ff. These complexes were used to achieve the C-center-selective alkynylation of nonactivated alkyl halides. Thus, this method uses iron complexes to forge substituted alkynes in a new practical synthesis just as the picture shows the forging of a samurai sword from iron.

Base Metal Complexes as Homogeneous Catalysts and Enzyme Mimics

This article is a short overview of some recent research activity in the Laboratory of Inorganic Synthesis and Catalysis (LSCI) at EPFL-ISIC. It summarizes the work on Ni-catalyzed cross-coupling reactions of non-activated alkyl halides. It then describes and discusses the work on the bio-mimetic chemistry of [Fe]-hydrogenase.

Kumada–Tamao–Corriu Coupling of Alkyl Halides Catalyzed by an Iron–Bisphosphine Complex

Abstract An iron(II) chloride complex possessing a sterically demanding ortho-phenylene-tethered bisphosphine ligand shows a high catalytic activity in the Kumada–Tamao–Corriu coupling of nonactivated alkyl halides with aryl Grignard reagents. Primary, secondary, and tertiary alkyl halides can participate as an electrophilic coupling partner. A radical clock experiment using (iodomethyl)cyclopropane exclusively gives the corresponding ring-opening coupling product, suggesting intermediacy of alkyl radical species.

Tuning Chemoselectivity in Iron‐Catalyzed Sonogashira‐Type Reactions Using a Bisphosphine Ligand with Peripheral Steric Bulk: Selective Alkynylation of Nonactivated Alkyl Halides

The incredible bulk: A highly C-center-selective alkynylation of nonactivated alkyl halides with the corresponding Grignard reagents is achieved by using the iron-phosphine complex 1. Primary and secondary alkyl iodides, bromides, and chlorides take part in the reaction to give the substituted alkynes in good to excellent yields. Sequential cyclization/cross-coupling reactions are also demonstrated.

Tuning Chemoselectivity in Iron-Catalyzed Sonogashira-Type Reactions Using a Bisphosphine Ligand with Peripheral Steric Bulk: Selective Alkynylation of Nonactivated Alkyl Halides

Tuning Chemoselectivity in Iron-Catalyzed Sonogashira-Type Reactions Using a Bisphosphine Ligand with Peripheral Steric Bulk: Selective Alkynylation of Nonactivated Alkyl Halides

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{C 6H 3-2,6-(OPPh 2) 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.

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.

ChemInform Abstract: Cross‐Coupling of Non‐Activated Alkyl Halides by a Nickel Pincer Complex

AbstractReview: 37 refs.

Nickel-catalyzed cross coupling of non-activated alkyl halides: a mechanistic perspective

Cross coupling of non-activated alkyl halides is a potentially transformative methodology in organic synthesis. Herein we review the recent development of nickel-catalyzed coupling of non-activated alkyl halides. The current understanding of the mechanism of these coupling reactions is highlighted. As the mechanism is ligand-dependant, the perspective is organized according to the types of ligands employed in the catalysis.

ChemInform Abstract: Iron‐Catalyzed Suzuki—Miyaura Coupling of Alkyl Halides.

AbstractA novel iron‐catalyzed Suzuki—Miyaura coupling of nonactivated alkyl halides with arylboron compounds is developed.

Cross-coupling of Grignard reagents with alkyl halides or tosylates by the use of nickel or palladium containing perovskite

Nickel and palladium-containing perovskites, LaFe 0.8Ni 0.2O 3 (LFNO) and LaFe 0.95Pd 0.05O 3 (LFPO), could be employed as effective catalyst sources for the cross-coupling of nonactivated alkyl halides and tosylates with Grignard reagents in the presence of conjugated dienes. The reaction proceeded efficiently at room temperature or below using only ca. 1 mol % of catalysts with respect to Ni or Pd and the perovskites were reused without considerable loss of activity.

Cross Coupling of Non-Activated Alkyl Halides by a Nickel Pincer Complex

Non-activated alkyl halides are challenging substrates for cross-coupling reactions because they are reluctant to undergo oxidative addition and because metal alkyl intermediates are prone to beta-H elimination. Despite recent progress, well-defined catalysts are rare. We recently prepared Ni complexes with a chelating pincer-type bis(amino)amide ligand. The chloride complex [((Me)NN2)NiCl] is an active (pre)catalyst for the coupling of non-activated alkyl halides with alkyl, aryl, and heteroaryl Grignard reagents. The catalysis tolerates a wide range of functional groups such as keto, ester, amide, acetal, indole, furan, nitrile, etc. The Ni complex also catalyzes direct alkylation of alkynes and aromatic heterocycles.

The Nickel/Copper‐Catalyzed Direct Alkylation of Heterocyclic CH 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.

ChemInform Abstract: Ni‐Catalyzed Sonogashira Coupling of Nonactivated Alkyl Halides: Orthogonal Functionalization of Alkyl Iodides, Bromides, and Chlorides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Ni-Catalyzed Sonogashira Coupling of Nonactivated Alkyl Halides

Ni-Catalyzed Sonogashira Coupling of Nonactivated Alkyl Halides

Ni-Catalyzed Sonogashira Coupling of Nonactivated Alkyl Halides

Corrected by: Ni-Catalyzed Sonogashira Coupling of Nonactivated Alkyl HalidesSynfacts 2010; 2010(01): 0127-0127DOI: 10.1055/s-0029-1219039

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.

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.

Catalysts for Cross‐Coupling Reactions with Non‐Activated Alkyl Halides

AbstractFor Abstract see ChemInform Abstract in Full Text.