Coupling Reactions Of Alkyl Halides Research Articles

Oxidative Substitution of Organocopper(II) by a Carbon-Centered Radical.

Copper-catalyzed coupling reactions of alkyl halides are believed to prominently involve copper(II) species and alkyl radicals as pivotal intermediates, with their exact interaction mechanism being the subject of considerable debate. In this study, a visible light-responsive fluoroalkylcopper(III) complex, [(terpy)Cu(CF3)2(CH2CO2tBu)] Trans-1, was designed to explore the mechanism. Upon exposure to blue LED irradiation, Trans-1 undergoes copper-carbon bond homolysis, generating Cu(II) species and carbon-centered radicals, where the carbon-centered radical then recombines with the Cu(II) intermediate, resulting in the formation of Cis-1, the Cis isomer of Trans-1. Beyond this, a well-defined fluoroalkylcopper(II) intermediate ligated with a sterically hindered ligand was isolated and underwent full characterization and electronic structure studies. The collective experimental, computational, and spectroscopic findings in this work strongly suggest that organocopper(II) engages with carbon-centered radicals via an "oxidative substitution" mechanism, which is likely the operational pathway for copper-catalyzed C-H bond trifluoromethylation reactions.

Nickel-Catalyzed Multicomponent Coupling Reaction of Alkyl Halides, Isocyanides and H2O: An Expedient Way to Access Alkyl Amides

We herein describe a Ni-catalyzed multicomponent coupling reaction of alkyl halides, isocyanides, and H2O to access alkyl amides. Bench-stable NiCl2(dppp) is competent to initiate this transformation under mild reaction conditions, thus allowing easy operation and adding practical value. Substrate scope studies revealed a broad functional group tolerance and generality of primary and secondary alkyl halides in this protocol. A plausible catalytic cycle via a SET process is proposed based on preliminary experiments and previous literature.

A Copper‐Catalyzed Sonogashira Coupling Reaction of Diverse Activated Alkyl Halides with Terminal Alkynes Under Ambient Conditions

AbstractWe describe a copper‐catalyzed Sonogashira coupling reaction of alkyl halides with terminal alkynes under ambient conditions, efficiently providing a versatile tool for the construction of substituted alkynes. A new proline‐based N,N,P‐ligand is utilized to promote the transformation under a mild reaction condition. Diverse alkyl halides, such as primary and secondary (hetero)benzyl chlorides and bromides, secondary and tertiary α‐bromo amides and propargylic bromide, are applicable to provide a wide array of alkynes.magnified image

Visible Light-Driven Cross Coupling Reactions Catalyzed By B12 Complex with Photosensitizer

Organometallic B12 compounds are unique metal complexes having a cobalt-carbon σ-bond present in biological systems [1]. Cleavage of the metal-organic σ-bond initiates many B12-dependent enzymatic reactions. The alkylated cobalt complex is generally formed by the reaction of the Co(I) state of the complex with electrophiles such as an organic halide in vivo. Therefore, the reductive formation of the Co(I) species followed by formal oxidative addition of the organic halide to form the alkylated cobalt complex are key steps for the development of the B12 catalyzed enzymatic reactions. Our group has been reported the photosensitizing formation of the Co(I) species of the B12 derivative, heptamethyl cobyrinate perchlorate, using various photosensitizers (PSs) such as, [Ru(bpy)3]Cl2 or cyclometalated iridium(III) complexes and performed various B12 model reactions such as 1,2-migration of functional groups, dechlorination and so on [2,3]. Here, a visible light driven Heck-type coupling reaction of alkyl halides with styrene and its derivatives catalyzed by the cobalamin derivative (B12) with the [Ru(bpy)3]Cl2 photosensitizer at room temperature is reported. The catalytic efficiencies of the B12 catalyst were compared to that of other cobalt complexes such as cobaloxime. Various control experiments supported a radical-based mechanism similar to those for typical B12 model reactions. An unique coupling reaction combined with 1,2-migration of the functional group is also reported. Mild reaction conditions using an environmentally benign cobalt catalyst derived from the natural B12 provided a practical protocol for the synthetic organic chemistry of the B12 catalyzed reaction system. [1] Reviews: a) H. Shimakoshi, Y. Hisaeda, Current Opinion in Electrochem. 2018, 8, 24; b) H. Shimakoshi, Y. Hisaeda, ChemPlusChem. 2017, 82, 17 (Back cover). [2] H. Tian, H. Shimakoshi, T. Ono, Y. Hisaeda, ChemPlusChem 2019, in press (Front cover). [3] H. Shimakoshi, Y. You, Y. Hisaeda et al, Dalton Trans. 2018, 47, 675 (Front cover).

Visible Light‐Driven, Room Temperature Heck‐Type Reaction of Alkyl Halides with Styrene Derivatives Catalyzed by B12 Complex

AbstractA visible light driven Heck‐type coupling reaction of alkyl halides with styrene and its derivatives catalyzed by the cobalamin derivative (B12) with the [Ru(bpy)3]Cl2 photosensitizer at room temperature is reported. The catalytic efficiencies of the B12 catalyst were compared to that of other cobalt complexes such as cobaloxime. Various control experiments supported a radical‐based mechanism similar to those for typical B12 model reactions. A unique coupling reaction combined with 1,2‐migration of the functional group is also reported. Mild reaction conditions using an environmentally benign cobalt catalyst derived from the natural B12 provided a practical protocol for the synthetic organic chemistry of the B12 catalyzed reaction system.magnified image

Copper Catalyzed Asymmetric Sonogashira Coupling Reaction of Alkyl Halides

Copper Catalyzed Asymmetric Sonogashira Coupling Reaction of Alkyl Halides

Nickel-catalyzed coupling reaction of alkyl halides with aryl Grignard reagents in the presence of 1,3-butadiene: mechanistic studies of four-component coupling and competing cross-coupling reactions.

We describe the mechanism, substituent effects, and origins of the selectivity of the nickel-catalyzed four-component coupling reactions of alkyl fluorides, aryl Grignard reagents, and two molecules of 1,3-butadiene that affords a 1,6-octadiene carbon framework bearing alkyl and aryl groups at the 3- and 8-positions, respectively, and the competing cross-coupling reaction. Both the four-component coupling reaction and the cross-coupling reaction are triggered by the formation of anionic nickel complexes, which are generated by the oxidative dimerization of two molecules of 1,3-butadiene on Ni(0) and the subsequent complexation with the aryl Grignard reagents. The C-C bond formation of the alkyl fluorides with the γ-carbon of the anionic nickel complexes leads to the four-component coupling product, whereas the cross-coupling product is yielded via nucleophilic attack of the Ni center toward the alkyl fluorides. These steps are found to be the rate-determining and selectivity-determining steps of the whole catalytic cycle, in which the C-F bond of the alkyl fluorides is activated by the Mg cation rather than a Li or Zn cation. ortho-Substituents of the aryl Grignard reagents suppressed the cross-coupling reaction leading to the selective formation of the four-component products. Such steric effects of the ortho-substituents were clearly demonstrated by crystal structure characterizations of ate complexes and DFT calculations. The electronic effects of the para-substituent of the aryl Grignard reagents on both the selectivity and reaction rates are thoroughly discussed. The present mechanistic study offers new insight into anionic complexes, which are proposed as the key intermediates in catalytic transformations even though detailed mechanisms are not established in many cases, and demonstrates their synthetic utility as promising intermediates for C-C bond forming reactions, providing useful information for developing efficient and straightforward multicomponent reactions.

Efficient phosphine-mediated formal C(sp3)-C(sp3) coupling reactions of alkyl halides in batch and flow.

The construction of C(sp3)-C(sp3) bond is an essential chemical transformation in synthetic chemistry due to its abundance in organic scaffolds. Here we demonstrate a valuable adaptation of the Wittig-type chemical procedure to efficiently facilitate C(sp3)-C(sp3) bond formation utilizing a range of alkyl building blocks. Additionally the method is amenable with flow synthesis to afford coupled products in good to excellent yields without laborious purification process.

Stereospecific Intramolecular Reductive Cross-Electrophile Coupling Reactions for Cyclopropane Synthesis.

The stereospecific reductive cross-electrophile coupling reaction of 2-aryl-4-chlorotetrahydropyrans to afford disubstituted cyclopropanes is reported. This ring contraction presents surprises with respect to the stereochemical outcome of reaction of the alkyl halide moiety. While cross-coupling and reductive cross-electrophile coupling reactions of alkyl halides are typically stereoablative, using a chiral catalyst to set the stereocenter, this transformation proceeds with high stereochemical fidelity at the alkyl halide and ether bearing stereogenic centers. This approach provides straightforward access to highly substituted cyclopropanes in two steps from commercially available aldehydes.

Acceleration of CuI-catalyzed coupling reaction of alkyl halides with aryl Grignard reagents using lithium chloride

In the presence of LiCl, CuI-catalyzed coupling reaction of R(alkyl)-X with Ar(aryl)MgBr at rt was completed within 2h. Effective leaving groups X in R-X were Br, I, OTs, but not Cl. Grignard reagents ArMgBr with both standard and bulky Ar such as 2-MeC6H4, 2-MeOC6H4, and 2,6-(Me)2C6H3 afforded the desired products in good yields. Ester and cyano groups in R-X were tolerated. Coupling reaction with R(alkyl)-MgBr proceeded as well.

ChemInform Abstract: Silver‐Catalyzed Coupling Reactions of Alkyl Halides with Indenyllithiums.

AbstractThe reaction, catalyzed by AgBr, is applied to a wide range of secondary and tertiary alkyl halides to afford the corresponding indene or fluorene [cf.

Silver-catalyzed coupling reactions of alkyl halides with indenyllithiums

Coupling reactions of tertiary and secondary alkyl halides with indenyllithiums proceeded effectively in the presence of a catalytic amount of silver bromide to provide tertiary- and secondary-alkyl-substituted indene derivatives in good yields.

Cobalt-Catalyzed Reductive Coupling of Saturated Alkyl Halides with Activated Alkenes

[reaction: see text] An efficient cobalt-catalyzed reductive coupling reaction of alkyl halides with electron-withdrawing alkenes (CH(2)=CR(1)EWG, EWG = electron-withdrawing group) in the presence of water and zinc powder in acetonitrile to give the corresponding Michael-type addition product (RCH(2)CR(1)EWG) was described. The methodology is versatile such that unactivated primary, secondary, and tertiary alkyl bromides and iodides and various conjugated alkenes including acrylates, acrylonitrile, methyl vinyl ketone, and vinyl sulfone all successfully participate in this coupling reaction. For the alkyl halides used in the reaction, the iodides generally gave better yields compared to those of the corresponding bromides. It is a unique method employing CoI(2)dppe, zinc, and alkyl halides, affording conjugate addition products in high yields. Mechanistically, the reaction appears to follow an oxidative addition driven route rather than the previously reported radical route.

Zr-Catalyzed Coupling Reaction of Alkyl Halides, Tosylates, and Sulfates with β-Phenethyl Grignard Reagents via Styrene-Zirconate Intermediates

β-Phenethylmagnesium chlorides react with alkyl halides, tosylates, and sulfates in the presence of a catalytic amount of Cp 2 ZrCl 2 to afford 2-arylalkanes via alkylation of styrene-zirconate intermediates at the benzylic position. Competitive reaction using mixtures of alkyl halides (alkyl-X; X = F, Cl, Br) showed that the reactivities of the halides increase in the order of alkyl-Cl < alkyl-F < alkyl-Br with the relative rates of 1: ] 9:428.

Cobalt‐Catalyzed Three‐Component Coupling Reaction of Alkyl Halides, 1,3‐Dienes, and Trimethylsilylmethylmagnesium Chloride.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Cobalt-catalyzed three-component coupling reaction of alkyl halides, 1,3-dienes, and trimethylsilylmethylmagnesium chloride.

[reaction: see text] A combination of CoCl(2) and 1,6-bis(diphenylphosphino)hexane catalyzes a novel three-component coupling reaction of alkyl bromides, 1,3-dienes, and silylmethylmagnesium chloride, yielding homoallylsilanes in good to excellent yields. The reaction involves a radical species from alkyl halides.

Phosphonium Chloride Catalyzed Dehydrochlorinative Coupling Reactions of Alkyl Halides with Hydridochlorosilanes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Cobalt‐Catalyzed Coupling Reaction of Alkyl Halides with Allylic Grignard Reagents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Phosphonium Chloride-Catalyzed Dehydrochlorinative Coupling Reactions of Alkyl Halides with Hydridochlorosilanes

The dehydrochlorinative Si−C coupling reactions of various primary and secondary alkyl chlorides with hydridochlorosilanes in the presence of tetrabutylphosphonium chloride as catalyst gave the coupling products with elimination of HCl as a gas. Coupling reactions of activated alkyl chlorides such as benzyl chlorides proceeded at 130 °C, while unactivated organic chlorides such as silylalkyl chlorides and secondary alkyl chlorides required higher reaction temperatures of 150 or 170 °C and longer reaction times. Primary alkyl chlorides reacted with trichlorosilane (1) to give coupling products in good to excellent yields, but secondary alkyl chlorides reacted at a slower rate and gave lower yields of products. Coupling reactions with methyldichlorosilane instead of 1 proceeded at slower rates and gave lower yields of products.

Cobalt-catalyzed coupling reaction of alkyl halides with allylic grignard reagents.

Facile construction of quaternary carbon centers: The cobalt-catalyzed coupling reaction of not only primary and secondary but also tertiary alkyl halides with allylic Grignard reagents proceeds smoothly (see scheme; dppp=1,3-bis(diphenylphosphanyl)propane; R=primary, secondary, or tertiary alkyl group). A radical mechanism is proposed for the oxidative addition of alkyl halides to cobalt. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z19929_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.