Cu-catalyzed Cross-coupling Reactions Research Articles

Copper-Catalyzed Homocoupling of Boronic Acids: A Focus on B-to-Cu and Cu-to-Cu Transmetalations

Controlling and understanding the Cu-catalyzed homocoupling reaction is crucial to prompt the development of efficient Cu-catalyzed cross-coupling reactions. The presence of a coordinating base (hydroxide and methoxide) enables the B-to-Cu(II) transmetalation from aryl boronic acid to CuIICl2 in methanol, through the formation of mixed Cu-(μ-OH)-B intermediates. A second B-to-Cu transmetalation to form bis-aryl Cu(II) complexes is disfavored. Instead, organocopper(II) dimers undergo a coupled transmetalation-electron transfer (TET) allowing the formation of bis-organocopper(III) complexes readily promoting reductive elimination. Based on this mechanism some guidelines are suggested to control the undesired formation of homocoupling product in Cu-catalyzed cross-coupling reactions.

C–N cross-coupling organic transformations catalyzed via copper oxide nanoparticles: A review (2016-present)

• Role of copper oxide nanoparticles as catalyst in organic transformations. • C–N coupling reactions catalysed by CuO nanoparticles. • Year wise comprehensive overview of the CuO- catalyzed C–N coupling reactions from 2016 to present. Molecules that contain nitrogen are very important because of their tremendous role in the synthesis of heterocycles, medicinal chemistry, natural products, ligands, and catalyst synthesis. In synthetic chemistry research, Cu-catalyzed cross-coupling reactions that create C–N bonds have become a significant method for the fabrication of anilines and aniline derivatives as well as the most important class of nitrogen-containing compounds. The demand for nitrogen-containing molecules increases day by day in material chemistry and chemical biology. The C–N bond formation is crucial because it allows the entrance of nitrogen into the organic compounds, and it is extremely vital in aromatic compounds and has proven difficult for synthetic chemists. Nanomaterials catalyzed C–N coupling have attracted researchers very much due to their greener approach. The present review depicts a comprehensive overview of the copper oxide nanoparticles catalyzed C–N bond formation (2016-Present). This would be very useful for the researcher working with Cu-containing nanoparticles in catalysis, cross-coupling reactions, etc.

Unsymmetric monothiooxalamides from S8, bromodifluoro reagents and anilines: Synthesis and applications

Unsymmetric monothiooxamides as very special and important scaffolds have been widely existing in natural products and bioactive molecules. However, the efficient construction of such compounds are very rare. Herein, we report a simple and practical strategy to achieve unsymmetric monothiooxalamides via S8-mediated defluorination and vulcanization of amines with bromodifluoroalkylative reagents under mild conditions. And the potential applications of such compounds as ligands has been demonstrated in Cu-catalyzed cross coupling reactions. The fluorinated quinoxalinones, benzooxazinone, α-phenyliminoamides, as well as 2-amidobenzothiazoles are obtained in-situ from unsymmetric monothiooxalamides, in which bromodifluoroalkylative reagents undertake selective triple cleavage. Moreover, we also discover that N-aryl-2-amidobenzothiazoles have aggregation-induced luminescence (AIE) characteristics, which might have great potential in the fields of sensing, imaging, diagnosis and treatment.

Unlocking the Friedel-Crafts arylation of primary aliphatic alcohols and epoxides driven by hexafluoroisopropanol

Unlocking the Friedel-Crafts arylation of primary aliphatic alcohols and epoxides driven by hexafluoroisopropanol

Copper-Catalyzed Methoxylation of Aryl Bromides with 9-BBN-OMe.

A Cu-catalyzed cross-coupling reaction between aryl bromides and 9-BBN-OMe to provide aryl methyl ethers under mild conditions is reported. The oxalamide ligand BHMPO plays a key role in the transformation. Various functional groups on bromobenzenes are well tolerated, providing the desired anisole products in moderate to high yields.

Two benzothiadiazole-based compounds as multifunctional fluorescent sensors for detection of organic amines and anions

Two benzothiadiazole-based compounds, namely 4,7-di(1H-1,2,4-triazol-1-yl)benzo-[2,1,3]thiadiazole (1) and 4,7-di(1H-pyrazol-1-yl)benzo-[2,1,3]thiadiazole (2), have been constructed with Cu-catalyzed cross-coupling reactions. The fluorescence studies show that compound 1 has high selectivity and sensitivity toward TEA (triethylamine), EDA (ethylenediamine), TMEDA (N,N,N’,N’-tetramethylethylenediamine), MnO4− and ClO− by fluorescence quenching, and compound 2 also has high selectivity and sensitivity toward TEA and TMEDA via fluorescence quenching. The calculated detection limits of 1 for TEA, EDA, TMEDA, MnO4− and ClO− are 0.129, 0.635, 0.320, 9.820 and 12.740 μM, respectively. Meanwhile, the detection limits of compound 2 for TEA and TMEDA are 0.400 and 0.278 μM, respectively. Interestingly, compounds 1 and 2 are the first fluorescent sensors for the selective recognition of TMEDA.

Phthalimide-Carried Disulfur Transfer To Synthesize Unsymmetrical Disulfanes via Copper Catalysis

A versatile Cu-catalyzed cross-coupling reaction to various unsymmetrical disulfanes has been presented, from phthalimide-carried disulfur transfer reagents and commercially available boronic acids...

Two benzothiadiazole-based fluorescent sensors for selective detection of Cu2+ and OH– ions

Two benzothiadiazole-based compounds, namely 4,7-di(1H-imidazol-1-yl)benzo-[2,1,3]thiadiazole (1) and 4,7-di(1H-pyrazol-1-yl)benzo-[2,1,3]thiadiazole (2), have been synthesized via Cu-catalyzed cross-coupling reaction, which can be used to detect Cu2+ and OH– by fluorescence quenching with high selectivity and sensitivity, respectively. The detection limits were determined to be 0.11 μM for Cu2+ and 55 μM for OH–. Furthermore, two compounds have cell permeability and 1 could be used for Cu2+ detection in living cells.

Synthesis of 3-Substituted 3-Bromo-1-phenylallenes from Alkynylcycloheptatrienes.

A new method has been developed for the preparation of 3-bromo-1-phenylallenes from 7-alkynylcycloheptatrienes and N-bromosuccinimide. Trisubstituted bromoallenes were obtained at room temperature in moderate to excellent yields. Functionalization of the carbon-bromine bond via Pd- or Cu-catalyzed cross-coupling reactions easily provided substituted allenes.

Cu-catalyzed cross-coupling reactions of vinyl epoxide with organoboron compounds: access to homoallylic alcohols.

Copper-catalyzed cross-coupling reactions of vinyl epoxide with arylboronates to obtain aryl-substituted homoallylic alcohols are described. The reaction selectivity was different to that of previously reported vinyl epoxide ring-opening reactions using aryl nucleophiles. The reaction proceeded under mild conditions, affording aryl-substituted homoallylic alcohols with high selectivity and in good to excellent yields. The reaction provides convenient access to aryl-substituted homoallylic alcohols from vinyl epoxide

Three-Coordinate Copper(II) Aryls: Key Intermediates in C-O Bond Formation.

Copper(II) aryl species are proposed key intermediates in Cu-catalyzed cross-coupling reactions. Novel three-coordinate copper(II) aryls [CuII]-C6F5 supported by ancillary β-diketiminate ligands form in reactions between copper(II) alkoxides [CuII]-OtBu and B(C6F5)3. Crystallographic, spectroscopic, and DFT studies reveal geometric and electronic structures of these Cu(II) organometallic complexes. Reaction of [CuII]-C6F5 with the free radical NO(g) results in C-N bond formation to give [Cu](η2-ONC6F5). Remarkably, addition of the phenolate anion PhO- to [CuII]-C6F5 directly affords diaryl ether PhO-C6F5 with concomitant generation of the copper(I) species [CuI](solvent) and {[CuI]-C6F5}-. Experimental and computational analysis supports redox disproportionation between [CuII]-C6F5 and {[CuII](C6F5)(OPh)}- to give {[CuI]-C6F5}- and [CuIII](C6F5)(OPh) unstable toward reductive elimination to [CuI](solvent) and PhO-C6F5.

The Role of PEG on Pd- and Cu-Catalyzed Cross-Coupling Reactions

Carbon–carbon and carbon–heteroatom coupling reactions are among the most important transformations in organic synthesis as they enable complex structures to be formed from readily available compounds under different routes and conditions. Several metal-catalyzed cross-coupling reactions have been developed creating many efficient methods accessible for the direct formation of new bonds between differently hybridized carbon atoms.During the last decade, much effort has been devoted towards improvement of the sustainability of these reactions, such as catalyst recovery and atom efficiency. Polyethylene glycol (PEG) can be used as a medium, as solid-liquid phase transfer catalyst, or even as a polymer support. PEG has been investigated in a wide variety of cross-coupling reactions either as an alternative solvent to the common organic solvents or as a support for catalyst, substrate, and ligand. In this review we will summarize the different roles of PEG in palladium- and copper-catalyzed cross-coupling reactions, with the focus on Heck, Suzuki–Miyaura, Sonogashira, Buchwald–Hartwig, Stille, Fukuyama, and homocoupling reactions. We will highlight the role of PEG, the preparation of PEGylated catalysts and substrates, and the importance for the reaction outcome and applicability.1 Introduction2 PEG in Heck Reactions3 PEG in Homocoupling Reactions4 PEG in Suzuki–Miyaura Reactions5 PEG in Sonogashira Reactions6 PEG in Buchwald–Hartwig Reactions7 PEG in Stille Reactions8 PEG in Fukuyama Reactions9 PEG in Miscellaneous Cross-Coupling Routes10 Conclusions

ChemInform Abstract: Maximizing the Reactivity of Phenolic and Aminic Radical‐Trapping Antioxidants: Just Add Nitrogen!

AbstractReview: 37 refs.

Maximizing the reactivity of phenolic and aminic radical-trapping antioxidants: just add nitrogen!

Hydrocarbon autoxidation, the archetype free radical chain reaction, challenges the longevity of both living organisms and petroleum-derived products. The most important strategy in slowing this process is via the intervention of radical-trapping antioxidants (RTAs), which are abundant in nature and included as additives to almost every petroleum-derived product as well as several other commercial products. Accordingly, a longstanding objective of many academic and industrial scientists has been the design and development of novel RTAs that can outperform natural and industrial standards, such as α-tocopherol, the most biologically active form of vitamin E, and dialkylated diphenylamines, respectively. Some time ago we recognized that attempts to maximize the reactivity of phenolic RTAs had largely failed because substitution of the phenolic ring with electron-donating groups to weaken the O-H bond and accelerate the rate of H atom transfer to radicals leads to compounds that are unstable in air. We surmised that incorporating nitrogen into the phenolic ring would render them more stable to one-electron oxidation, enabling their substitution with strong electron-donating groups. Guided by computational chemistry, we demonstrated that replacing the phenyl ring in very electron-rich phenols with either 3-pyridyl or 5-pyrimidyl rings leads to phenolic-like RTAs with good air stability and great reactivity. In fact, rate constants determined for the reactions of some compounds with peroxyl radicals were almost 2 orders of magnitude greater than those for α-tocopherol and implied that the reactions proceeded without an enthalpic barrier. Following extensive thermochemical and kinetic characterization, we took our studies of these compounds to more physiologically relevant media, such as lipid bilayers and human low density lipoproteins, where the heterocyclic analogues of vitamin E shone, displaying unparalleled abilities to inhibit lipid peroxidation and prompting their current investigation in animal models of degenerative disease. Moreover, we carried out studies of these compounds in several industrially relevant contexts and in particular demonstrated that they could be used synergistically with less reactive, less expensive, phenolic RTAs. More recently, our attention has turned to the application of these ideas to maximizing the reactivity of diarylamine RTAs that are common in additives to petroleum-derived products, such as lubricating oils, transmission and hydraulic fluids, and rubber. In doing so, we have developed the most reactive diarylamines ever reported. The 3-pyridyl- and 5-pyrimidyl-containing diarylamines are easily accessed using Pd- and/or Cu-catalyzed cross-coupling reactions, and display an ideal compromise between reactivity and stability. The most reactive compounds are characterized by rate constants for reactions with peroxyl radicals that are independent of temperature, implying that-as for the most reactive heterocyclic phenols-these reactions proceed without an enthalpic barrier. Unprecedented reactivity was also observed when hydrocarbon autoxidations were carried out at elevated temperatures, real-world conditions where diarylamines are uniquely effective because of a catalytic RTA activity that makes use of the hydrocarbon substrate as a sacrificial reductant. Our studies to date suggest that heterocyclic diarylamines have real potential to increase the longevity of petroleum-derived products in a variety of applications where diphenylamines are currently used.

Cu-Catalyzed cross-coupling reactions of epoxides with organoboron compounds

A copper-catalyzed cross-coupling reaction of epoxides with arylboronates is described. This reaction is not limited to aromatic epoxides, because aliphatic epoxides are also suitable substrates. In addition, N-sulfonyl aziridines can be successfully converted into the products. This reaction provides convenient access to β-phenethyl alcohols, which are valuable synthetic intermediates.

Enantioselective synthesis of chiral isotopomers of 1-alkanols by a ZACA-Cu-catalyzed cross-coupling protocol.

Chiral compounds arising from the replacement of hydrogen atoms by deuterium are very important in organic chemistry and biochemistry. Some of these chiral compounds have a non-measurable specific rotation, owing to very small differences between the isotopomeric groups, and exhibit cryptochirality. This particular class of compounds is difficult to synthesize and characterize. Herein, we present a catalytic and highly enantioselective conversion of terminal alkenes to various β and more remote chiral isotopomers of 1-alkanols, with ≥99 % enantiomeric excess (ee), by the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA) and Cu-catalyzed cross-coupling reactions. ZACA-in situ iodinolysis of allyl alcohol and ZACA-in situ oxidation of TBS-protected ω-alkene-1-ols protocols were applied to the synthesis of both (R)- and (S)-difunctional intermediates with 80-90 % ee. These intermediates were readily purified to provide enantiomerically pure (≥99 % ee) compounds by lipase-catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of various chiral isotopomers of 1-alkanols in excellent enantiomeric purity (≥99 % ee) by introducing deuterium-labeled groups by Cu-catalyzed cross-coupling reactions without epimerization.

ChemInform Abstract: Cu‐Mediated Enamide Formation in the Total Synthesis of Complex Peptide Natural Products

AbstractReview: 131 refs.

Cu-mediated enamide formation in the total synthesis of complex peptide natural products

Cu-mediated C(sp(2))-N bond formation has received intense interest recently, and has been applied to the total synthesis of a wide variety of structurally complex natural products. This review covers the synthetic assembly of peptide natural products in which Cu-mediated enamide formation is the key transformation. The total syntheses of cyclopeptide alkaloids, pacidamycin D, and yaku'amide A exemplify the versatility of the Cu-catalyzed cross-coupling reaction in comparison to other synthetic methods.

The synthesis of chiral fluorinated 4-alkyl-4′-[(4-alkylphenyl)ethynyl]biphenyls

Abstract We have designed, synthesized, and evaluated the physical properties of new fluorinated phenyltolane based chiral liquid crystal materials with 2-methylbutyl chains. This type of fluoro-substitution in chemical combination with a phenyltolane core brings a surprising improvement to the mesomorphic properties. The investigated compounds exhibit broad temperature ranges for the N∗ phase and very low melting points. All homologues exhibited Blue Phase. We have applied a Cu-catalyzed cross-coupling reaction between aryl Grignard reagents and alkyl bromides for the synthesis of the products.

A Very Active Cu-Catalytic System for the Synthesis of Aryl, Heteroaryl, and Vinyl Sulfides

cis-1,2-Cyclohexanediol (L3) has been shown to be an efficient and versatile bidentate O-donor ligand that provides a highly active Cu-catalytic system. It was more effective than diols such as trans-1,2-cyclohexanediol or ethylene glycol. This commercially available cis-1,2-cyclohexanediol ligand facilitated the Cu-catalyzed cross-coupling reactions of alkyl, aryl, or heterocyclic thiols with either alkyl, aryl, heterocyclic, or substituted vinyl halides. This new catalytic system promoted the mild and efficient stereo- and regiospecific synthesis of biologically important vinyl sulfides. The yields obtained using electron-rich substituted vinyl sulfides with this catalyst system are generally 75-98%. Most importantly, this singular catalyst system is extremely versatile and provides entry into a wide range of sulfides. This method is particularly noteworthy given its mild reaction conditions, simplicity, generality, and exceptional level of functional group tolerance.