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Cobalt-catalyzed cross-coupling of alkynyl Grignard reagents with alkenyl triflates
Abstract
Alkenyl triflates in combination with Co(acac)(3) as a catalyst were found to be excellent coupling partners of alkynyl Grignard reagents, where no special additives (even a phosphine ligand) but a common solvent, THF, are required to obtain variously substituted enynes.
... Only triflate 11 was isolated as a solution in tetrahydrofuran (THF) (Scheme 5). The vinylation of alkynylmagnesium bromide 14 can be performed using vinyl nonaflate in the presence of a cobalt catalyst to produce enyne 15 (Scheme 6) [108]. The optimized reaction conditions have a significantly broader scope, although enyne 15 was prepared in a near-quantitative isolated yield. ...
This review summarizes the applications of vinyl sulfonate and vinyl acetate as green alternatives for vinyl bromide in cross-coupling reactions. In the first part, the preparation of vinyl sulfonates and their cross-coupling reactions are briefly discussed. Then, a brief review of vinyl acetate cross-coupling reactions, including cyclization reactions, the Fujiware–Moritani reaction, and transvinylation reactions are described.
Conjugated alkynes are valuable intermediates in the synthesis of natural products, agrochemicals, pharmaceuticals, fine chemicals, and organic molecular materials. Since its introduction in 1975, the palladium‐catalyzed Sonogashira reaction has become the primary choice for the construction of sp–sp ² carbon–carbon bonds in aryl‐, heteroaryl‐, and alkenyl‐substituted alkynes. A vast range of reaction conditions have been explored to expand and optimize the scope of the Sonogashira reaction, including sustainable variants, microwave‐assisted cross couplings, and cross couplings performed in water. Research efforts also target the development of improved catalytic systems for the Sonogashira reaction, such as solid‐supported palladium catalysts and nanoparticles, the use of N ‐heterocyclic carbenes (NHCs) as ligands, as well as copper‐free variants of the reaction. This Chapter reviews the application of the palladium‐catalyzed Sonogashira cross coupling of terminal alkynes with aryl or alkenyl halides and triflates. Coupling reactions that form conjugated alkynes via alternative methods, or use different electrophiles, catalysts, or alkynes, are also briefly described.
The transition metal-catalyzed C-C and C-X (X=heteroatom) homo and cross-coupling reactions were pioneered as a momentous strategy for the total synthesis of natural products, agrochemicals, pharmaceuticals, etc. Among the various transition metal-catalyzed coupling reactions, manganese held a distinctive identity owing to its earth-abundance and eco-friendliness apart from its unique characteristics. Despite having many synthetic advancements, exploiting manganese as a catalyst for coupling reactions has recently gained pivotal gravity. An in-depth comprehension of the molecular mechanism of the chemical reaction will provide further insight to optimize the reaction conditions. The mechanisms adopted by Mn-catalyzed couplings are found to differ from other first-row transition metal counterparts. Hence in this article, we provide the state-of-the-art on the detailed theoretical aspects of manganese-catalyzed carbon-carbon (C-C) and carbon-heteroatom (C-X; X=Si) coupling reactions.
NHC-mediated deoxygenation of alcohols under photocatalytic conditions is described. The process provides various alkyl radicals, which can react with 1-Bromoalkyne via Csp3-Csp coupling reaction to afford internal alkynes in moderate...
Transition-metal-catalyzed cross-coupling reactions have been an essential strategy for the construction of C—C bonds, including in the syntheses of pharmaceuticals and natural products, since the pioneering work of Heck, Negishi, and Suzuki, among others. Of the widely applied catalysts based on group 8–10 metals, economical cobalt salts have been shown to be advantageous as an alternative to other commonly used expensive and/or toxic catalysts. In this review, cobalt-catalyzed cross-coupling reactions of organometallic reagents, such as organomagnesium or organozinc derivatives, to achieve the formation of C—C bonds, are summarized. Furthermore, various methods for the cobalt-catalyzed reductive cross coupling of C—X/C—O electrophiles have also been reported for selective C—C bond formation, and these are also discussed.
Transition metal-catalyzed formation of C–C bonds was one of the most important methods in chemical synthesis since the pioneering work of Heck, Negishi, and Suzuki. Now, cross-coupling reactions involving Csp2 electrophiles are commonplace in both industrial and academic research. With the development in this field, cheap and less toxicologically benign cobalt catalyst attracted more and more attention, and displays a high catalytic activity in many cases and a low tendency to produce homocoupling and β-elimination by-products. In this chapter, we will introduce the Co-catalyzed cross-coupling of Csp2 electrophiles with organometallic reagents (like Grignard reagent, organozinc, organoboron, etc.) to construct Csp2–C bonds, as well as the Co-catalyzed reductive cross-couplings involving two electrophiles.KeywordsCatalysisC–C bonds formationCobaltCsp2 electrophileGrignard reagentOrganoboronOrganozincReductive cross-couplings
Cobalt-catalyzed hydroalkynylation of alkynes, alkenes, and imines affords internal alkynes with various functional groups adjacent to the carbon–carbon triple bond moiety in an atom-economical manner. In addition, cross-coupling of in situ generated alkynylcobalt species from terminal alkynes, haloalkynes, and metal acetylides with (hetero)aromatic compounds and organic halides selectively provides various internal aryl- and alkylalkynes.
1 Introduction
2 Hydroalkynylation of Alkynes for 1,3-Enyne Synthesis
3 Hydroalkynylation of Polar and Nonpolar Double Bonds
4 Dehydrogenative Cross-Coupling Reaction Using Terminal Alkynes with Aromatic Compounds
5 Cross-Coupling Reactions Using Haloalkynes as the Coupling Partners
6 Cross-Coupling Reactions Using Metal Acetylides
7 Conclusion
C(aryl)-OMe bond functionalization catalyzed by cobalt(II) chloride in combination with a nacnac-type ligand and magnesium as a reductant is reported. Borylation and benzoylation of aryl methoxides are demonstrated, and C(aryl)-SMe bond borylation can be achieved under similar conditions. This is the first example of achieving these transformations using cobalt catalysis. Mechanistic studies suggest that a Grignard reagent is generated as an intermediate in a rare example of a magnesiation via a C-O bond activation reaction. Indeed, an organomagnesium species could be directly observed by electrospray ionization mass spectroscopic analysis. Kinetic experiments indicate that a heterogeneous cobalt catalyst performs the C-O bond activation.
Asymmetric cross-electrophile coupling has emerged as a promising tool for producing chiral molecules; however, the potential of this chemistry with metals other than nickel remains unknown. Herein, we report a cobalt-catalyzed enantiospecific vinylation reaction of allylic alcohol with vinyl triflates. This work establishes a new method for the synthesis of enantioenriched 1,4-dienes. The reaction proceeds through a dynamic kinetic coupling approach, which not only allows for direct functionalization of allylic alcohols but also is essential to achieve high chemoselectivity. The use of cobalt enables the reactions to proceed with high enantiospecificity, which have failed to be realized by nickel catalysts.
The Co-catalyzed reactions of 2-halobenzamides and alkynes to form isoquinolones or 2-vinyl benzamides are described. Formation of the two selective products can be fully controlled by adopted ligands. Study of...
Transition-metal-catalyzed cross-coupling of organohalides, ethers, sulfides, amines, and alcohols (and derivatives thereof) with Grignard reagents, known as the Kumada–Tamao–Corriu reaction, can be used to prepare important intermediates in the synthesis of numerous biologically active compounds. The most frequently used transition metals are nickel, palladium, and iron, but there are several examples for cross-coupling reactions catalyzed by copper, cobalt, manganese, chromium, etc. salts and complexes. The aim of this review is to summarize the most important transition-metal-catalyzed cross-coupling reactions realized in the period 2000 to 2020.
1 Introduction
2 Nickel Catalysis
3 Palladium Catalysis
4 Iron Catalysis
5 Catalysis by Other Transition Metals
5.1 Cobalt Catalysis
5.2 Copper Catalysis
5.3 Manganese Catalysis
5.4 Chromium Catalysis
6 Conclusion
Vinylsilanes were directly prepared from the corresponding vinyl triflates under magnesium-promoted reductive conditions in THF with no transition metal catalyst, and gem-bis-silylated compounds were obtained in NMP. Investigation of the redox potential of starting materials and products suggested that reductive coupling reactions of vinyl triflates might be controlled by the reduction potential. A variety of gem-bis-silylated compounds and 3-silyladipic acid esters were easily synthesized in only two steps from vinyl triflates in high yields.
An efficient Co-catalyzed 1,4-addition reaction of alkyl/aryl triflates and tosylates with activated alkenes is described. In this reaction, air-stable cobalt(II) complex, mild reducing agent Zn and simple proton source (H2O)...
Introduction Methods of Preparation of Magnesium Organometallics Transition-Metal-Catalyzed Cross-Coupling Reactions of Organomagnesium Reagents Conclusions Experimental Procedures References
This chapter provides an overview of the most recent advances in the preparation of polar organometallic compounds (containing alkali metals, magnesium, and zinc), characterized by little if no stabilization, and their reactivity with alkylating agents. After a general introduction on the direct alkylation of alkyl and alkenyl polar organometallics, the chapter focuses on allylation and carbometalation reactions, including diastereo- and enantioselective processes, and finally discusses some of the most updated examples of cross-coupling transformations employing magnesium and zinc organometallics.
Conjugated aryl and vinyl acetylenes have been known for a long time as valuable intermediates and targets in the synthesis of pharmaceuticals, natural products, molecular electronics, and machinery. The main goal of this overview is to spot the most user-friendly and practical catalytic system allowing synthesis of substituted alkynes and their recent manifold applications in organic synthesis.
The C-Br bond of 2-bromothiophene was successfully cleavaged by tetrakis(trimethylphosphine) cobalt(0). Penta-coordinate cobalt(II) bromide complex 1 (α-C4H3S)CoBr(PMe3)3 as C-Br bond activation product was obtained. The molecular and crystal structures of complex 1 were determined by single-crystal X-ray diffraction. Complex 1 belongs to the orthorhombic crystal system, space group Pnma with a = 20.428(4), b =11.036(2), c = 9.201(2) Å, V = 2074.3(7) Å3, Z = 4, Dc = 1.442 g/cm3, μ = 0.401 mm-1, F(000) = 924 and T = 273 K. Complex 1 was also characterized by elemental analysis, IR, UV-Vis, photoluminescence (PL) spectroscopy and TGA.
The stereoselective transformation of alpha-alkoxyacetoaldehydes to the corresponding (Z)-vinyl triflates was achieved by treatment with phenyl triflimide and DBU. The stereochemistry was explained by the "syn-effect," which was attributed primarily to an sigma -> pi* interaction. The,beta-alkoxy vinyl triflates obtained were applied to the stereoselective synthesis of structurally diverse (Z)-allylic alcohols via transition metal-catalyzed cross-coupling reaction and [1,2]-Wittig rearrangement.
Cobalt(II)-catalyzed C(sp(2) )O cross-coupling between aryl/heteroaryl alcohols and vinyl/aryl halides in the presence of Cu(I) has been achieved under ligand-free conditions. In this reaction, copper plays a significant role in transmetalation rather than being directly involved in the CO coupling. This unique Co/Cu-dual catalyst system provides an easy access to a library of aryl-vinyl, heteroaryl-styryl, aryl-aryl, and heteroaryl-heteroaryl ethers in the absence of any ligand or additive.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Cobalt(II) iodide, bromide, and chloride react with 1 equiv. of IPr [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] to form a series of tetrahedral dimeric (30e) complexes of cobalt(II) in good yields. These were transformed into the monomeric forms in the presence of pyridine. These complexes were characterized by SQUID, XPS, UV/Vis spectroscopy, elemental analysis, and X-ray crystallography, and were found to have high catalytic activity for Kumada–Tamao–Corriu cross-coupling reactions of aryl halides.
A divalent cobalt iodine complex bearing 1,3-bis(mesityl)imidazol-2-ylidene and pyridine ligands was synthesized and its structure was determined. The cobalt center has a typical d7-tetrahedral geometry, as expected. Catalytic application of this cobalt complex with bromoalkanes and Grignard reagents demonstrated high-yield formation of alkenes as a result of β-hydrogen elimination; in sharp contrast, the activation of alkyl halides was not successful using the larger N-heterocyclic carbene ligand, 1,3-bis(2,6-diisopropyl-phenyl)imidazol-2-ylidene. In the presence of styrene, Heck reaction proceeded with trans selectivity. The reaction of a substrate containing a bromobenzyl moiety yielded a homocoupling product.
A highly effective synthesis of 2,3-fused pyrroles from cyclic ketones has been achieved. The transformation includes a rhodium-catalyzed reaction of 4-alkenyl-1-sulfonyl-1,2,3-triazoles featuring an unusual 4π electrocyclization. The methodology was further extended to the synthesis of indoles using a one-pot reaction starting from 1-ethynylcyclohexenes.
Take your pick…︁ A practical method for the synthesis of structurally diverse rhodium vinylcarbenes from stable 1-sulfonyl-1,2,3-triazole precursors has been developed. The reaction is general for a broad range of 4-alkenyl triazoles and dienes, enabling the stereoselective synthesis of a variety of polycyclic imines, which are readily converted into amines or aldehydes in a one-pot process.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
Co(acac)3-PPh3 was found to effectively catalyze the C(sp2)-C(sp2) coupling of Grignard reagents to give alkenyl-arenes and conjugated dienes, utilizing close affinity towards alkenyl triflates.
The recent developments in cobalt catalysis are compiled in this review covering the years 2000 through 2007. Special focus is directed towards cobalt-catalysed ring-formation reactions as well as towards cobalt-catalysed (cross-) coupling reactions and synthetically useful applications thereof in the synthesis of acyclic compounds.
1 Introduction
2 Cobalt-Catalysed Cycloaddition Reactions
2.1 Cyclopropanation
2.2 Four-Membered-Ring Formation
2.3 Five-Membered-Ring Formation
2.4 Six-Membered-Ring Formation
2.5 Seven-Membered-Ring Formation
2.6 Eight-Membered-Ring Formation
2.7 Ten-Membered-Ring Formation
3 Cobalt-Catalysed Synthesis of Acyclic Compounds
3.1 Coupling Reactions between Alkenes and Alkynes
3.2 Cross-Coupling Reactions
3.3 Cobalt-Catalysed Coupling Reactions Using Grignard Reagents
3.4 Hydrocyanation, Hydrophosphination, Hydrosilylation and Hydrovinylation Reactions
3.5 Nucleophilic Substitution with Organocobalt Reagents
3.6 Cobalt-Catalysed Carbonylative Ring-Expansion and Ring-Opening Reactions
4 Miscellaneous
5 Conclusions and Outlook
Secondary amines react with N-aromatic 2-chlorides in the presence of a catalytic amount of cobalt chloride. When DPPP was added as ligand, the yield was further improved. The N-aromatic-containing tertiary amines formed are interesting due to their potential biological activity. This work represents the first cobalt-catalyzed approach to C–N bond formation involving N-aromatic 2-chlorides and secondary amines having a certain amount of versatility and functional group tolerance.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
An operationally simple cross-coupling reaction between aryl halides and alkyl halides with high selectivity has been developed. The underlying domino process utilizes CoCl2/Me4-DACH as a catalyst system. The methodology exhibits high sustainability as it obviates the need for the pre-formation and handling of stoichiometric amounts of hazardous Grignard compounds.
Matrix metalloproteinases (MMPs) are important factors in gliomas since these enzymes facilitate invasion into the surrounding brain and participate in neovascularization. In particular, the gelatinases (MMP-2 and MMP-9), and more recently MMP-25, have been shown to be highly expressed in gliomas and have been associated with disease progression. Thus, inhibition of these MMPs may represent a promising non-cytotoxic approach to glioma treatment. We report herein the synthesis and biological evaluation of a series of 4-butylphenyl(ethynylthiophene)sulfonamido-based hydroxamates. Among the new compounds tested, a promising derivative, 5a, was identified, which exhibits nanomolar inhibition of MMP-2, MMP-9, and MMP-25, but weak inhibitory activity toward other members of the MMP family. This compound also exhibited anti-invasive activity of U87MG glioblastoma cells at nanomolar concentrations, without affecting cell viability.
Cobalt(iii) complexes, [CoCl(2)(L1)(2)](PF(6)) (1, L1 = N-methyl-N-(2-pyrimidinyl)imidazolylidene), [CoCl(L2)(2)](PF(6))(2) (, L2 = N-picolyl-(2-pyrimidinyl)imidazolylidene), [Co(L3)(2)](PF(6))(3) (3, L3 = bis(N-2-pyrimidylimidazolylidenyl)methane) and [CoCl(2)(L3)](PF(6)) (4) have been prepared from the corresponding pyrimidine functionalized imidazolium salts [HL1](PF(6)), [HL2](PF(6)), and [H(2)L3](PF(6))(2)via in situ generated silver carbene complexes under mild conditions. These cobalt complexes were characterized by (1)H and (13)C NMR spectroscopy and X-ray diffraction analysis. The cobalt complexes have been found to be good catalyst precursors for Kumada-Corriu cross-coupling reactions of aryl halides and Grignard reagents at room temperature. Complex 1 is more active under the mild conditions.
In the presence of a ruthenium catalyst, alkenyl triflates were found to be transformed to the corresponding bromides, chlorides and iodides simply by treatment with a lithium halide (1.2 equiv.).
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
Cobalt-catalyzed cross-coupling reactions are very efficient for the elaboration of Csp2-Csp2 bonds and are especially interesting for couplings involving alkyl halides. Kharasch described the first cobalt-catalyzed alkenylation of aromatic Grignard reagents in 1943. In 1998, Cahiez reinvestigated the cobalt-catalyzed alkenylation of aromatic Grignard reagents. Recently, Hayashi described the cobalt-catalyzed cross-coupling between alkenyl triflates and alkenyl Grignard reagents. In 1983, Uemura described the cross-coupling between diaryltellurides (Ar2Te) and aromatic organomagnesium reagents in the presence of cobalt salts. The reaction affords poor yields, and a substantial amount of homocoupling product accruing from the Grignard reagent is produced. Iron-catalyzed cross coupling between aryl Grignard reagents and functionalized secondary alkyl bromides generally failed whereas excellent yields are obtained under cobalt catalysis.
The first cobalt-catalyzed N-arylation of nitrogen heterocycles with electrophilic aryl halides in water mediated by a combination of readily available and cheap CoCl2·6H2O with the chelating diamine was reported. Investigation of the ligand system show that the reaction proceeds through a biphasic system with the best yield achieved when the reaction is carried out using a combination of CoCl2·6H 2O and N,N'-dimethylethylenediamine (dmeda). Aryl iodides are found to be more reactive than aryl bromides as electophilic counterpart in the coupling reactions, producing the products in much higher yields. Heterocycles, such as indole and 7-azaindole are found to be effective nucleophilic counterparts for the coupling process and produce N-phenyl derivatives.
In the presence of 0.5-1 mol % of FeCl(3) with lithium bromide as a crucial additive, alkynyl Grignard reagents, prepared from the corresponding alkynes and methylmagnesium bromide, react with alkenyl bromides or triflates to give the corresponding conjugated enynes in high to excellent yields. The reaction shows wide applicability to various terminal alkynes and alkenyl electrophiles.
In the last few years, we and other groups have demonstrated that economical cobalt salts can advantageously replace expensive and toxic catalysts for cross coupling reactions. These cobalt-catalyzed reactions have considerably extended the range of functionalized compounds. A variety of sensitive functional groups can be tolerated in these coupling reactions and various organic compounds RX could be involved (R = alkyl, alkynyl, aryl, allyl and X = halides: F, Cl, Br, I and even triflates). Here, we describe our contributions in this area for the preparation of a broad range of functionalized compounds from organometallic species or by direct cross-coupling.
The reaction of trimethylsilylmethylmagnesium chloride (TMSCH2MgCl) with 1,2-dihalogenoethylene in the presence of 1 mol % of Co(II) or Co(III) acetylacetonate in THF or THF–NMP proceeded exclusively in a mono-coupling pathway to provide 3-trimethylsilyl-1-halogeno-1-propene with >99% of E geometry in high yield, which was converted to a variety of γ-substituted allylsilanes by Ni- or Pd-catalyzed coupling with organometallic compounds.
Vinyliodide (I) kondensieren mit Vinylgrignardverbindungen (II) zu den Dienen (III).
A series of 1-alkynes (RC≡CH where R=Et, n-Pr, n-Bu, n-C6H13, cyclohexyl, Ph, Me3Si, Me3SiCH2, and Me3SiOCH2) was found to dimerize regioselectively (>99%) to 2,4-disubstituted 1-buten-3-ynes in 92–99% yields by catalysis of (η5-C5Me5)2TiCl2/i-PrMgBr at 30 °C in 1–3 h. The catalyst system is also effective for the regioselective codimerization of various 1-alkynes with 1-ethynylcyclohexene or ethynylbenzene.
A new access to Z-1,3-enynes is reported through condensation of Z-vinyl carbamates with magnesium bromide acetylides under Ni(0) catalysis. Yields ranging from 40 to 80% as well as Z/E ratios from 75:25 to more than 95:5 are obtained. A new preparation of Z-vinyl carbamates from E-allyl carbamates is also described.
Organozinc halides and diorganozincs undergo cross-coupling reactions with either E- or Z-alkenyl iodides in the presence of catalytic amounts of Co(acac)2 or Co(acac)3 in THF:NMP at 55 °C leading to polyfunctional alkenes with retention of the stereochemistry of the double bond.
Alkenyl iodides, bromides and chlorides react with organomagnesium reagents in THF, in the presence of Co(acac)2 and NMP (9 to 4 equiv.), to give the cross-coupling products in good yields. The reaction is chemoselective (aryl or alkyl bromides, esters and ketones) and stereoselective (≥99.5%).
Benzylic halides coupled with 1-alkynylmagnesium halides in the presence of a catalytic amount of Co(acac)3 to provide 1-aryl-2-alkynes in moderate to good yield.
The coupling reaction of aryl iodides with terminal alkynes by using a catalyst system of CuI-PPhs in the presence of K2CO3 as base gives the corresponding arylated alkynes in excellent yields. Addition of PPh3 is essential for the reaction to proceed catalytically. Vinyl iodides also react smoothly with the alkynes to give enyne compounds with retention of the configurations. While DMF and DMSO can be used as solvents, DMSO is found to be effective for the reaction with aliphatic terminal alkynes. A reaction mechanism involving initial formation of copper acetylide species coordinated by PPh3 followed by reaction of aryl and vinyl iodides is proposed.
For Abstract see ChemInform Abstract in Full Text.
For Abstract see ChemInform Abstract in Full Text.
Reactions of 2-alkenyl methyl ether with phenyl, trimethylsilylmethyl, and allyl Grignard reagents in the presence of cobalt(II) complexes are discussed. The success of the reactions heavily depends on the combination of the substrate, ligand, and Grignard reagent. In the reaction of cinnamyl methyl ether, the formation of the linear coupling products predominates over that of the relevant branched products. In the cobalt-catalyzed allylation of allylic ethers, addition of a diphosphine ligand can change the regioselectivity, mainly providing the corresponding branched products. Rhodium complexes catalyze the reactions of allylic ethers and halides with allylmagnesium chloride and allylzinc bromide, respectively, in which the branched coupling product is the major product.
Treatment of cinnamyl methyl ether with phenylmagnesium bromide in ether in the presence of CoCl2[1,5-bis(diphenylphosphino)pentane] affords 1,3-diphenylpropene in good yield. Similar allylic substitution reaction with trimethylsilylmethylmagnesium chloride proceeded smoothly to yield homoallylsilanes. alpha,beta-Unsaturated aldehyde acetal also underwent allylic substitution.
Two new cyclic peroxides (1 and 2) and the known metabolite 3 have been found in the organic extract of the Indian sponge Acarnus bicladotylota. The structure of the new products has been assured by chemical and spectroscopic methods. The absolute stereochemistry of 1-3 has been determined by Mosher's method on the semisynthetic derivative 4.
Oral terbinafine treatment for superficial fungal infections of toe and fingernails is associated with a low incidence (1:45000) of hepatobiliary dysfunction. Due to the rare and unpredictable nature of this adverse drug reaction, the mechanism of toxicity has been hypothesized to be either an uncommon immunological or metabolically mediated effect. However, there is little evidence to support either mechanism, and toxic metabolites of terbinafine have not been identified. We incubated terbinafine with both rat and human liver microsomal protein in the presence of GSH and were able to trap an allylic aldehyde, 7,7-dimethylhept-2-ene-4-ynal (TBF-A), which corresponds to the N-dealkylation product of terbinafine. TBF-A was also prepared synthetically and reacted with excess GSH to yield conjugates with HPLC retention times and mass spectra identical to those generated in the microsomal incubations. The major GSH conjugate, characterized by (1)H NMR, corresponds to addition of GSH in a 1,6-Michael fashion. There remains a second electrophilic site on this metabolite, which can bind either to a second molecule of GSH or to cellular proteins via a 1,4-Michael addition mechanism. Moreover, we demonstrated that the formation of the GSH conjugates was reversible. We speculate that this allylic aldehyde metabolite, formed by liver enzymes and conjugated with GSH, would be transported across the canalicular membrane of hepatocytes and concentrated in the bile. The mono-GSH conjugate, which is still reactive, could bind to hepatobiliary proteins and lead to direct toxicity. Alternatively, it could modify canalicular proteins and lead to an immune-mediated reaction causing cholestatic dysfunction.
A brief overview of the scope of the four major protocols with respect to the electrophilic cross-coupling partners is presented in somewhat irrespective of relative merit and demerits among these protocols. Thus, some noteworthy recent advances in which more critical comparisons among the four protocols mentioned will made are discussed. In addition, some recent methodological developments with emphasis on searches for superior phosphine and other ligands as well as one mechanistic aspects of the Pd-catalyzed alkynylation are discussed as well.
The aerial parts of Nanodea muscosa, collected in Chile, yielded two new acetylenic acids. Their structures were elucidated by spectroscopic analyses, including 2D NMR techniques, as (13E)-octadec-13-en-11-ynoic acid (1) and (2E)-octadec-2-en-4-ynedioic acid (2). Compound 2 constitutes the first example of a conjugated ene-yne fatty diacid isolated from a natural source. Compounds 1 and 2 did not exhibit toxicity toward a panel of DNA damage checkpoint defective yeast mutants or show affinity for the 5-HT(1A), 5-HT(2A), D(2), and H(1) receptors.
[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.
[reaction: see text] We report a copper(I)-catalyzed procedure for the synthesis of 1,3-enynes. This method affords a variety of enynes in good to excellent yields. This method can tolerate a variety of functional groups, does not require the use of expensive additives, and is palladium-free.
Details of cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic Grignard reagents are disclosed. A combination of cobalt(II) chloride and 1,2-bis(diphenylphosphino)ethane (DPPE) or 1,3-bis(diphenylphosphino)propane (DPPP) is suitable as a precatalyst and allows secondary and tertiary alkyl halides--as well as primary ones--to be employed as coupling partners for allyl Grignard reagents. The reaction offers a facile synthesis of quaternary carbon centers, which has practically never been possible with palladium, nickel, and copper catalysts. Benzyl, methallyl, and crotyl Grignard reagents can all couple with alkyl halides. The benzylation definitely requires DPPE or DPPP as a ligand. The reaction mechanism should include the generation of an alkyl radical from the parent alkyl halide. The mechanism can be interpreted in terms of a tandem radical cyclization/cross-coupling reaction. In addition, serendipitous tandem radical cyclization/cyclopropanation/carbonyl allylation of 5-alkoxy-6-halo-4-oxa-1-hexene derivatives is also described. The intermediacy of a carbon-centered radical results in the loss of the original stereochemistry of the parent alkyl halides, creating the potential for asymmetric cross-coupling of racemic alkyl halides.
The Sonogashira coupling reaction catalyzed by ultrafine nickel(0) powder has been developed; terminal alkynes couple with aryl, alkenyl iodide and aryl bromide in the presence of cuprous iodide, triphenylphosphine, potassium hydroxide and ultrafine particle nickel(0) to provide the corresponding cross-coupling products with high yields.
A cobalt-diamine complex catalyzes the cross-coupling reactions of primary and secondary alkyl halides with aryl Grignard reagents. It is confirmed that oxidative addition of alkyl halide to cobalt proceeds via a radical process. Optically pure Ueno-Stork halo acetals undergo diastereoselective cross-coupling reactions, the products of which are transformed into optically active THF derivatives. A sequential radical cyclization/arylation reaction under cobalt catalysis provides extremely short access to a synthetic prostaglandin AH13205.
[reaction: see text] Organocopper compounds prepared by the transmetalation of functionalized arylmagnesium halides with CuCN.2LiCl undergo smooth cross-coupling reactions with aryl fluorides and tosylates bearing a carbonyl function in the ortho position in the presence of Co(acac)(2) (7.5 mol %), Bu(4)NI (1 equiv), and 4-fluorostyrene (20 mol %) as promoters in DME/THF/DMPU leading to polyfunctional aromatics or heterocycles.
A cobalt complex, [CoCl2(dpph)] (DPPH = [1,6-bis(diphenylphosphino)hexane]), catalyzes an intermolecular styrylation reaction of alkyl halides in the presence of Me3SiCH2MgCl in ether to yield beta-alkylstyrenes. A variety of alkyl halides including alkyl chlorides can participate in the styrylation. A radical mechanism is strongly suggested for the styrylation reaction. The sequential isomerization/styrylation reactions of cyclopropylmethyl bromide and 6-bromo-1-hexene provide evidence of the radical mechanism. Crystallographic and spectroscopic investigations on cobalt complexes reveal that the reaction would begin with single electron transfer from an electron-rich (diphosphine)bis(trimethylsilylmethyl)cobalt(II) complex followed by reductive elimination to yield 1,2-bis(trimethylsilyl)ethane and a (diphosphine)cobalt(I) complex. The combination of [CoCl2(dppb)] (DPPB = [1,4-bis(diphenylphosphino)butane]) catalyst and Me3SiCH2MgCl induces intramolecular Heck-type cyclization reactions of 6-halo-1-hexenes via a radical process. On the other hand, the intramolecular cyclization of the prenyl ether of 2-iodophenol would proceed in a fashion similar to the conventional palladium-catalyzed transformation. The nonradical oxidative addition of carbon(sp2)-halogen bonds to cobalt is separately verified by a cobalt-catalyzed cross-coupling reaction of alkenyl halides with Me3SiCH2MgCl with retention of configuration of the starting vinyl halides. The cobalt-catalyzed intermolecular radical styrylation reaction of alkyl halides is applied to stereoselective variants. Styrylations of 1-alkoxy-2-bromocyclopentane derivatives provide trans-1-alkoxy-2-styrylcyclopentane skeletons, one of which is optically pure.
[reaction: see text] This paper describes cobalt-mediated cross-coupling reactions of alkyl halides with 1-(trimethylsilyl)ethenylmagnesium bromide and 2-(trimethylsilyl)ethynylmagnesium bromide, respectively. The cobalt system allows for employing secondary as well as primary alkyl halides as the substrates. The reactions offer facile formations of alkyl-alkenyl and alkyl-alkynyl bonds. The reaction mechanism would include single-electron transfer from a cobalt complex to alkyl halide to generate the corresponding alkyl radical. The cobalt system thus enables sequential radical cyclization/alkenylation and cyclization/alkynylation reactions of 6-halo-1-hexene derivatives.
18 (m, 3 H) 13 C NMR (125 MHz, CDCl 3 ) δ 4
- Hz
Hz, 2 H), 6.82 (bs, 1 H), 7.00-7.06 (m, 1 H), 7.07-7.18 (m, 3 H). 13 C NMR (125 MHz,
CDCl 3 ) δ 4.5, 7.5, 27.5, 27.8, 93.7, 107.7, 121.2, 126.4, 126.6, 127.4, 127.7, 133.6, 134.0,
134.9. Anal. Calcd for C 18 H 24 Si: C, 80.53; H, 9.01. Found: C, 80.41; H, 8.79.
- H Akita
- A Yasuda
- Nakamura
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- T Mandai
- Y Matsumoto
- S Tsujiguchi
- J Matsuoka
- Tsuji
Mandai, T. Matsumoto, Y. Tsujiguchi, S. Matsuoka and J. Tsuji, J. Organomet. Chem., 1994,
473, 343-352.
- M Barluenga
- J M Yus
- P Concellon
- F Bernad
- Alvarez
Barluenga, M. Yus, J. M. Concellon, P. Bernad and F. Alvarez, J. Chem. Res. S, 1985,
128-129.
- L Feuerstein
- H Chahen
- M Doucet
- Santelli
Feuerstein, L. Chahen, H. Doucet and M. Santelli, Tetrahedron, 2006, 62, 112-120.
- R J Kasatkin
- Whitby
. Kasatkin and R. J. Whitby, J. Am. Chem. Soc., 1999, 121, 7039-7049.
- H Nishimura
- Y Araki
- S Maeda
- Uemura
Nishimura, H. Araki, Y. Maeda and S. Uemura, Org. Lett., 2003, 5, 2997-2999.
- N Thorand
- Krause
. Thorand and N. Krause, J. Org. Chem., 1998, 63, 8551-8553.
51 (d, J = 8.0 Hz, 2 H) 13 C NMR (125 MHz, CDCl 3 ) δ 14
- Hz
Hz, 2 H), 6.67 (bs, 1 H), 6.97 (d, J = 7.9 Hz, 1 H), 7.24-7.37 (m, 5 H), 7.51 (d, J = 8.0 Hz,
2 H). 13 C NMR (125 MHz, CDCl 3 ) δ 14.0, 19.7, 22.5, 27.5, 28.2, 28.6, 28.8, 31.4, 81.9, 89.7,
89.9, 93.7, 121.7, 123.2, 123.4, 125.9, 128.1, 128.3, 129.9, 130.4, 131.3, 131.6, 134.1, 134.6.
HRMS (APCI) Calcd for C 24 H 26 : [M+K] +, 353.166609. Found: m/z 353.166646.
(m, 4 H), 1.43 (quint, J = 7.2 Hz, 2 H), 1.57 (quint
- Mhz
MHz, CDCl 3 ) δ 0.91 (t, J = 6.9 Hz, 3 H), 1.24-1.42 (m, 4 H), 1.43 (quint, J = 7.2 Hz, 2 H),
1.57 (quint, J = 7.3 Hz, 2 H), 2.38 (t, J = 7.2 Hz, 2 H), 2.42 (t, J = 8.2 Hz, 2 H), 2.82 (t, J =
- T Mandai
- T Matsumoto
- Y Tsujiguchi
- S Matsuoka
- J Tsuji
T. Mandai, T. Matsumoto, Y. Tsujiguchi, S. Matsuoka and J. Tsuji, J. Organomet. Chem., 1994,
473, 343-352.
- J Barluenga
- M Yus
- J M Concellon
- P Bernad
- F Alvarez
J. Barluenga, M. Yus, J. M. Concellon, P. Bernad and F. Alvarez, J. Chem. Res. S, 1985,
128-129.
- M Feuerstein
- L Chahen
- H Doucet
- M Santelli
M. Feuerstein, L. Chahen, H. Doucet and M. Santelli, Tetrahedron, 2006, 62, 112-120.
- A Kasatkin
- R J Whitby
A. Kasatkin and R. J. Whitby, J. Am. Chem. Soc., 1999, 121, 7039-7049.
- T Nishimura
- H Araki
- Y Maeda
- S Uemura
T. Nishimura, H. Araki, Y. Maeda and S. Uemura, Org. Lett., 2003, 5, 2997-2999.
- S Thorand
- N Krause
S. Thorand and N. Krause, J. Org. Chem., 1998, 63, 8551-8553.
- Mizutani
- Wang
- Tsuji
- Ohmiya