Cross-coupling Reactions Of Alkyl Halides Research Articles

Air-Stable Iron-Based Precatalysts for Suzuki-Miyaura Cross-Coupling Reactions between Alkyl Halides and Aryl Boronic Esters.

The development of an air-stable iron(III)-based precatalyst for the Suzuki-Miyaura cross-coupling reaction of alkyl halides and unactivated aryl boronic esters is reported. Despite benefits to cost and toxicity, the proclivity of iron(II)-based complexes to undergo deactivation via oxidation or hydrolysis is a limiting factor for their widespread use in cross-coupling reactions compared to palladium-based or nickel-based complexes. The new octahedral iron(III) complex demonstrates long-term stability on the benchtop as assessed by a combination of 1H NMR spectroscopy, Mössbauer spectroscopy, and its sustained catalytic activity after exposure to air. The improved stability of the iron-based catalyst facilitates an improved protocol in which Suzuki-Miyaura cross-coupling reactions of valuable substrates can be assembled without the use of a glovebox and access a diverse scope of products similar to reactions assembled in the glovebox with iron(II)-based catalysts.

The Effect of Added Ligands on the Reactions of [Ni(COD)(dppf)] with Alkyl Halides: Halide Abstraction May Be Reversible.

The reactions of dppf-nickel(0) with alkyl halides proceed via three-coordinate nickel(0) intermediates of the form [Ni(dppf)(L)]. The effects of the identity of the added ligand (L) on catalyst speciation and the rates of reactions of [Ni(COD)(dppf)] with alkyl halides have been investigated using kinetic experiments and density functional theory calculations. A series of monodentate ligands have been investigated in attempts to identify trends in reactivity. Sterically bulky and electron-donating ligands are found to decrease the reaction rate. It was found that (i) the halide abstraction step is not always irreversible and the subsequent recombination of a nickel(I) complex with an alkyl halide can have a significant effect on the overall rate of the reaction and (ii) some ligands lead to very stable [Ni(dppf)(L)2] species. The yields of prototypical (dppf)nickel-catalyzed Kumada cross-coupling reactions of alkyl halides are significantly improved by the addition of free ligands, which provides another important variable to consider when optimizing nickel-catalyzed reactions of alkyl halides.

Unexpected Nickel Complex Speciation Unlocks Alternative Pathways for the Reactions of Alkyl Halides with dppf-Nickel(0).

The mechanism of the reactions between dppf-Ni0 complexes and alkyl halides has been investigated using kinetic and mechanistic experiments and DFT calculations. The active species is [Ni(κ2-dppf)(κ1-dppf)], which undergoes a halide abstraction reaction with alkyl halides and rapidly captures the alkyl radical that is formed. The rates of the reactions of [Ni(COD)(dppf)] with alkyl halides and the yields of prototypical nickel-catalyzed Kumada cross-coupling reactions of alkyl halides are shown to be significantly improved by the addition of free dppf ligand.

Iron-catalyzed Alkyl–Alkyl Negishi Coupling of Organoaluminum Reagents

The first iron-catalyzed cross-coupling reaction of alkyl halides with alkylaluminum reagents (alkyl–alkyl Negishi coupling) is developed using an iron/bisphosphine catalyst system. The reaction sh...

Visible light-driven cross-coupling reactions of alkyl halides with phenylacetylene derivatives for C(sp3)-C(sp) bond formation catalyzed by a B12 complex.

Visible light-driven cross-coupling reactions of alkyl halides with phenylacetylene and its derivatives catalyzed by the cobalamin derivative (B12) with the [Ir(dtbbpy)(ppy)2]PF6 photocatalyst at room temperature are reported. The robust B12 catalyst and Ir photocatalyst provided high turnover numbers of over 33 000 for the reactions.

Cross-coupling Reaction of Alkyl Halides with Alkyl Grignard Reagents Catalyzed by Cp-Iron Complexes in the Presence of 1,3-Butadiene

Iron-catalyzed cross-coupling reaction of alkyl halides with alkyl Grignard reagents by the combined use of cyclopentadienyl ligand and 1,3-butadiene additive is described. The reaction smoothly proceeds at room temperature using unactivated alkyl bromides and fluorides via non-radical mechanism, which is in sharp contrast with hitherto known Fe-catalyzed cross-coupling reactions of alkyl halides.

Iron Pincer Complexes as Catalysts and Intermediates in Alkyl–Aryl Kumada Coupling Reactions

Iron-catalyzed alkyl–aryl Kumada coupling has developed into an efficient synthetic method, yet its mechanism remains vague. Here, we apply a bis(oxazolinylphenyl)amido pincer ligand (Bopa) to stabilize the catalytically active Fe center, resulting in isolation and characterization of well-defined iron complexes whose catalytic roles have been probed and confirmed. Reactivity studies of the iron complexes identify an Fe(II) “ate” complex, [Fe(Bopa-Ph)(Ph)2]−, as the active species for the oxidative addition of alkyl halide. Experiments using radical-probe substrates and DFT computations reveal a bimetallic and radical mechanism for the oxidative addition. The kinetics of the coupling of an alkyl iodide with PhMgCl suggests that formation of the “ate” complex, rather than oxidative addition, is the turnover-determining step. This work provides insights into iron-catalyzed cross-coupling reactions of alkyl halides.

The Cobalt-Catalyzed Cross-Coupling Reaction of Alkyl Halides with Alkyl Grignard Reagents: A New Route to Constructing Quaternary Carbon Centers­

The cross-coupling of alkyl (pseudo)halides with alkyl Grignard reagents is catalyzed efficiently by a cobalt(II) chloride–lithium iodide–1,3-diene catalytic system, which provides a new synthetic tool for constructing sp3 carbon chains. This system is particularly useful for creating quaternary carbon centers via the use of tertiary alkyl Grignard reagents. Various functional groups including esters, amides and carbamates are well tolerated.

Imidazolidinium ferrate complexes: Synthesis and catalytic properties

Abstract The new well-defined and air stable anionic iron complexes bearing an imidazolidinium ligand (2a–d) have been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction studies. Starting from FeBr2, [imidazolidinium][FeBr4] complexes 2a and 2b were prepared. The reaction of imidazolidinium chlorides with Fe(OAc)2, followed by a recrystallization in the air led to bis(imidazolidinium) μ-oxido-bis[trichloroferrate(III)] complexes 2c and 2d. The catalytic activity of these novel complexes has been evaluated in the cross-coupling reactions of alkyl halides with Grignard reagents.

Zinc‐Catalyzed Borylation of Primary, Secondary and Tertiary Alkyl Halides with Alkoxy Diboron Reagents at Room Temperature

A new catalytic system based on a Zn(II) NHC precursor has been developed for the cross-coupling reaction of alkyl halides with diboron reagents, which represents a novel use of a Group XII catalyst for CX borylation. This approach gives borylations of unactivated primary, secondary, and tertiary alkyl halides at room temperature to furnish alkyl boronates, with good functional-group compatibility, under mild conditions. Preliminary mechanistic investigations demonstrated that this borylation reaction seems to involve one-electron processes.

NickelButadiene Catalytic System for the Cross‐Coupling of Bromoalkanoic Acids with Alkyl Grignard Reagents: A Practical and Versatile Method for Preparing Fatty Acids

Fatty acids are essential to natural life because they act as key components in biological membranes and glycerides, as well as in various biologically active agents, such as prostaglandins and endocannabinoids. For the construction of structurally diverse carbon frameworks of fatty acids, transition-metal-catalyzed cross-coupling reactions appear to be the most straightforward and efficient methods for carbon carbon bond formation and they have been employed in the synthesis of a wide variety of fatty acids with unsaturated bonds. However, these methods are limited to reactions at sp or sp carbon atoms, in which the stereochemistry of the olefinic moieties that are being introduced must be controlled. In contrast to these reactions, cross-coupling reactions between sp-hybridized carbon centers appear to be a useful and, potentially, more-promising tool, because they are applicable to the synthesis of both saturated and unsaturated fatty acids and they are free from the problems associated with double-bond stereochemistry. However, owing to the lower tolerance of the carboxylic group toward organometallic reagents, including transition-metal complexes, protected carboxy groups or their synthetic equivalents are often employed. Herein, we report a convenient and efficient one-pot procedure for the construction of carbon frameworks of fatty acids by using the nickelcatalyzed cross-coupling of alkyl halides that contain a carboxy functionality with Grignard reagents in the presence of 1,3-butadiene as an additive, in combination with an in situ protection procedure. As an example of a synthetic application of this method, the regioisomers of elaidic acid were synthesized through an iterative cross-coupling procedure. In our previous studies, we reported that the Ni-catalyzed cross-coupling reactions of alkyl halides with alkyl Grignard reagents in the presence of butadienes were effective for the construction of hydrocarbon skeletons that contained aprotic polar functionalities, such as ketones, esters, and nitriles. When alkyl halides that contained a carboxylic acid group are subjected to this cross-coupling reaction, without employing tedious protection-deprotection processes, the deprotonation of the carboxylic acid group is unavoidable. Thus, to develop a simple and straightforward route to fatty acids with various carbon chains, we examined the Ni-catalyzed cross-coupling reactions of 6-bromohexanoic acid (1a) with excess amounts of nBuMgCl under various conditions and we found that the expected decanoic acid was obtained in quantitative yield as the sole product, with no evidence of any undesirable side reactions, when the reaction was conducted at 0 8C for 1 h in the presence of 2.4 equivalents of nBuMgCl (Scheme 1). In this reaction, a

Iron-Catalyzed Cross-Coupling Reaction of Alkyl Halides with Biphenyl Grignard Reagent

Iron-Catalyzed Cross-Coupling Reaction of Alkyl Halides with Biphenyl Grignard Reagent

Fe-catalysed Kumada-type alkyl–alkyl cross-coupling. Evidence for the intermediacy of Fe(i) complexes

A novel Fe–NHC catalytic system allows the alkyl–alkyl cross-coupling reaction of alkyl halides and alkylmagnesium reagents has been developed. To our knowledge, this is the first Fe-catalysed Kumada-type coupling for the formation of C(sp3)–C(sp3) bonds in the presence of functional groups. The process takes place under mild conditions, avoiding the formation of β-elimination products. Mechanistic studies suggest the intermediacy of Fe(I) complexes, formed by reduction with the Grignard reagent, as the active species.

ChemInform Abstract: Pd‐Catalyzed Cross‐Coupling Reactions of Alkyl Halides

AbstractReview: 87 refs.

Cross-coupling Reaction of Grignard Reagents with Alkyl Halides Catalyzed by Green, Economical Copper Bromide Catalyst

For the first time a systematic research on the catalytic activity of CuXn(X=Cl, Br, I; x=1,2) for the cross-coupling reaction of alkyl halides with Grignard reagents was carried out and environmentally friendly, economical CuBr2showed highest catalytic activity among the catalyst. The conditions of the cross-coupling reaction were studied. The suitable amount of catalyst, reaction temperature and time are 0.3% mol (based on alkyl halide), 67°C (reflux), 6 h, respectively. Under the optimal conditions, the yields of the cross-coupling could reach up to 93%. Moreover, Grignard reagent with an electron-rich group reacted rapidly and with an electron-withdrawing group reacted sluggishly.

Pd-catalyzed cross-coupling reactions of alkyl halides

Cross-coupling reactions have become indispensable tools for creating carbon-carbon (or heteroatom) bonds in organic synthesis. Like in other important transition metal catalyzed reactions, such as metathesis, addition, and polymerization, unsaturated compounds are usually employed as substrates for cross-coupling reactions. However during the past decade, a great deal of effort has been devoted to the use of alkyl halides as saturated compounds in cross-coupling reactions, which has resulted in significant progress in this undeveloped area by introducing new effective ligands. Many useful catalytic systems are now available for synthetic transformations based on C(sp(3))-C(sp(3)), C(sp(3))-C(sp(2)) and C(sp(3))-C(sp) bond formation as complementary methods to conventional C(sp(2))-C(sp(2)), C(sp(2))-C(sp) and C(sp)-C(sp) coupling. This tutorial review summarizes recent advances in cross-coupling reactions of alkyl halides and pseudohalides catalyzed by a palladium complex.

Cross-Coupling Reaction of Alkyl Halides with Grignard Reagents Catalyzed by Ni, Pd, or Cu Complexes with π-Carbon Ligand(s)

Transition metal-catalyzed cross-coupling reactions of organic halides and pseudo-halides containing a C-X bond (X = I, Br, Cl, OTf, OTs, etc.) with organometallic reagents are among the most important transformations for carbon-carbon bond formation between a variety of sp, sp(2), and sp(3)-hybridized carbon atoms. In particular, researchers have widely employed Ni- and Pd-catalyzed cross-coupling to synthesize complex organic structures from readily available components. The catalytic cycle of this process comprises oxidative addition, transmetalation, and reductive elimination steps. In these reactions, various organometallic reagents could bear a variety of R groups (alkyl, vinyl, aryl, or allyl), but the coupling partner has been primarily limited to sp and sp(2) carbon compounds: alkynes, alkenes, and arenes. With alkyl coupling partners, these reactions typically run into two problems within the catalytic cycle. First, oxidative addition of alkyl halides to a metal catalyst is generally less efficient than that of aryl or alkenyl compounds. Second, the alkylmetal intermediates formed tend to undergo intramolecular beta-hydrogen elimination. In this Account, we describe our efforts to overcome these problems for Ni and Pd chemistry. We have developed new catalytic systems that do not involve M(0) species but proceed via an anionic complex as the key intermediate. For example, we developed a unique cross-coupling reaction of alkyl halides with organomagnesium or organozinc reagents catalyzed by using a 1,3-butadiene as the additive. This reaction follows a new catalytic pathway: the Ni or Pd catalyst reacts first with R-MgX to form an anionic complex, which then reacts with alkyl halides. Bis-dienes were also effective additives for the Ni-catalyzed cross-coupling reaction of organozinc reagents with alkyl halides. This catalytic system tolerates a wide variety of functional groups, including nitriles, ketones, amides, and esters. In addition, we have extended the utility of Cu-catalyzed cross-coupling reactions. With 1-phenylpropyne as an additive, Cu-catalyzed reactions of alkyl chlorides, fluorides, and mesylates with Grignard reagents proceed efficiently. These new catalytic reactions use pi-carbon ligands such as pi-allyl units or alkynes instead of heteroatom ligands such as phosphines or amines. Overall, these reactions provide new methodology for introducing alkyl moieties into organic molecules.

Vanadium-Catalyzed Cross-Coupling Reactions of Alkyl Halides with Aryl Grignard Reagents

Abstract Vanadium(III) chloride catalyzed cross-coupling reactions of alkyl halides with arylmagnesium bromides. Various arylmagnesium bromides, except for an ortho-substituted arylmagnesium reagent, could be used for the reaction. Among alkyl halides tested, cyclohexyl halides and primary alkyl halides were good substrates. The reactions likely proceed via carbon-centered radical intermediates.

Highly Selective Synthetic Reactions by the Combined Use of Organometallic Reagents and Radical Species

Abstract During these thirty years, we have pursued new methodologies in organic synthesis and developed many synthetically useful reactions. Among them, four topics are described in this article. (1) Regio- and stereoselective silylmetalation of acetylenes has been examined. Whereas platinum- or copper-catalyzed silylmagnesation of terminal acetylenes afforded (E)-1-silyl-1-alkene exclusively, palladium-catalyzed silylalumination with PhMe2Si-AlEt2 provided 2-silyl-1-alkenes with high regioselectivity. (2) Triethylborane induced radical addition of Ph3SnH to acetylenes gave 1-triphenylstannyl-1-alkenes in the presence of small amount of oxygen. The reaction has two distinguishing characteristics. One feature is that Et3B can initiate the radical reaction at low temperature, such as −78 °C. (3) The other distinctive feature of Et3B-induced radical reaction is that many solvents could be used for the reaction. Thus, water was chosen as a solvent, and Et3B-induced atom-transfer radical cyclization of iodo acetals and iodoacetates in water was examined. (4) Three types of organometallic ate complexes, R3MnMgBr, R3MgLi, and R3Co(L2)MgBr, were prepared and used for organic synthesis. Treatment of gem-dibromocyclopropane with trialkylmanganate provided alkylated cyclopropane after aqueous workup. Aryl and alkenyl halides could be converted into the corresponding magnesium reagents by the action of trialkylmagnesate via halogen–magnesium exchange. Finally, synthetic reactions catalyzed by cobalt complexes are described. Without suffering from β-elimination, cobalt complexes allow cross-coupling reactions of alkyl halides with Grignard reagents.

Fluoride-mediated selective cross-coupling reactions of alkyl halides and trimethyl(perfluoroalkyl)silanes, Me 3SiR f (R f = CF 3, C 2F 5) in the absence of any catalysts

A temperature range of −18 °C to room temperature was found to be effective for selective fluoride-mediated cross-coupling reactions of trimethyl(perfluoroalkyl)silanes, Me 3SiCF 3 and Me 3SiC 2F 5, and alkyl halides, RX (X = Br, I) in the absence of any catalyst.