In‐situ Generated and Premade 1‐Copper(I) Alkynes in Cycloadditions

The copper(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC) was discovered in 2002, which has become the most remarkable example for “click chemistry” to date. In CuAAC reaction, 1‐copper(I) alkyne has been recognized to be a key intermediate. However, many contradictory experimental results for this intermediate were reported in literature. For example, only the in‐situ generated 1‐copper(I) alkyne was used, while the premade 1‐copper(I) alkyne proved to be inefficient under the standard conditions. The kinetic studies indicated that CuAAC reaction had a strict second‐order dependence on Cu(I) and the DFT studies demonstrated that 1‐copper(I) alkyne intermediate should be a dinuclear copper(I) complex. But these results were inconsistent with the structure of the premade 1‐copper(I) alkyne. Although hundreds of structurally different ligands were reported to significantly enhance the efficiency of CuAAC reaction, their functions were assigned to prevent the oxidation and the disproportionation of Cu(I) ion. Based on the investigation of the references and our works, we proposed that the in‐situ generated 1‐copper(I) alkyne in CuAAC reaction is not identical with the premade 1‐copper(I) alkyne. The ligands may play dual roles to activate the 1‐copper(I) alkyne by blocking the polymerization of the in‐situ formed 1‐copper(I) alkynes and dissociating the polymeric structures of the premade 1‐copper(I) alkynes. As a result, we first disclosed that carboxylic acids can function as such activators and a novel carboxylic acid‐catalyzed CuAAC strategy was developed, which has been proven to be the most convenient and highly efficient CuAAC method to date. Furthermore, highly efficient and regioselective methods for the syntheses of 1,4,5‐trisubstituted 1,2,3‐triazoles were developed by using the premade 1‐copper(I) alkynes as substrates, in which the novel function of the premade 1‐copper(I) alkynes as excellent dipolarophiles was first disclosed and applied. In this article, a series of works reported by our group for the in‐situ generated and the premade 1‐copper(I) alkynes in cycloadditions are reviewed.     

Über Kupfer(I)-carboxylate und Chlorocuprate(I)

In mixtures of 7 vol. acetonitrile and 3 vol. acetic acid, solutions or suspensions of copper(II) acetate can be reduced with hydrazine hydrate to solutions of copper(I) acetate. In this way, purely white copper(I) acetate can be isolated. Other copper(I) carboxylates can be prepared by reduction of copper(II) carboxylates or by reaction of solid carboxylic acids with copper(I) acetate. By adding acetyl chloride to solutions of copper(I) acetate in acetonitrile/acetic acid mixtures, solutions of chlorocuprates(I) are formed. From these, highly pure copper(I) chloride can be obtained. By adding alkali acetate or tetramethyl ammonium chloride to solutions of chlorocuprates(I), the pure compounds Cs₃[Cu₂Cl₅], Rb₂[CuCl₃] and NMe₄[Cu₂Cl₃] were obtained.     

Sunlight‐Driven Copper‐Catalyst Activation Applied to Photolatent Click Chemistry

The synthesis, full characterization, photoreduction properties, and catalytic activity for the copper(I)‐catalyzed alkyne‐azide cycloaddition (CuAAC) reaction of a copper(II)–DMEDA (N,N′‐dimethylethylendiamine) complex is reported. Spectroscopic studies (UV/Vis, EPR) demonstrated that under daylight illumination highly effective copper(II) to copper(I) reduction occurs in this complex. These findings are in agreement with a high photoreduction quantum yield value of 0.22 in MeOH, and a value approaching unity as determined in THF. The reduction process, which can also be conducted by irradiation at 365 nm by using a standard TLC (thin layer chromatography) lamp, is ascribed to a highly efficient photoinduced electron transfer (PET) process mediated by the benzophenone photosensitizer present in the carboxylate counterion. Having deaerated the reaction mixture, the photogenerated copper(I) species proved to be highly active for the CuAAC reaction, demonstrated by reactions conducted with low catalyst loading (0.5 mol %) on a range of clickable protected and non‐protected mono‐ and disaccharides. Once initiated, the reaction can be stopped at any time on introducing air into the reaction medium. Deoxygenation followed by irradiation restores the activity, making the copper(II)–DMEDA complex a switchable catalyst of practical value.     

Coordination-synchronized trans-cis photoisomerization of bipyridylazobenzene driven by a Cu(II)/Cu(I) redox change

The trans-cis photoisomerization behavior of azobenzene-bipyridine ligand (dmpAB) was synchronized with coordination of the bipyridine moiety to copper. The coordination reaction can be reversibly controlled with reversible redox reaction of copper, to afford [Cu(dmpAB)(2)](+) in Cu(I) state and free dmpAB in Cu(II) state. UV irradiations to Cu(I) and Cu(II) samples form trans-rich and cis-rich compositions, respectively. The results enable us to control the trans-cis isomerization reversibly through Cu(II)/Cu(I) redox and a single UV light.     

Diaryliodonium salts as thermal initiators of cationic polymerization

Diaryliodonium salts (I) undergo efficient thermal decomposition in the presence of copper (II) compounds. Such systems can be employed as a novel class of latent thermal initiators for cationic polymerization. An investigation of the mechanism of the reaction demonstrated that the copper (II) compound is first reduced to the corresponding copper (I) compound, which subsequently reduces the diaryliodonium salt. The cationic polymerization of some typical monomers using these new initiators was carried out to demonstrate the scope of their utility.     

Cationic Copper(I) Complexes as Highly Efficient Catalysts for Single and Double A3‐Coupling Mannich Reactions of Terminal Alkynes: Mechanistic Insights and Comparative Studies with Analogous Gold(I) Complexes

Cationic Cu?L complexes (L=Buchwald‐type phosphane) with N co‐ligands have been characterised by structural and spectroscopic properties. These copper(I) complexes are extremely active catalysts, far more active than analogous gold(I) complexes, to promote the single and double A³ coupling of terminal alkynes, pyrrolidine and formaldehyde. The activity data show the possible ways in which the solvent can influence the catalytic performance by limiting complex solubility, by solvent decomposition or instability of the copper(I) redox state. Isolation of copper(I) complexes that are likely to be the key catalytic species has allowed light to be shed on the reaction mechanism.     

Copper-promoted enantioselective Reformatsky-type reaction with ketones

Controlled living polymerization of a broad range of monomers is a radical process known as ATRP (atom transfer radical polymerization) and is mediated by a variety of metals. A complex of copper has been found to be the most efficient catalyst, with a copper(I)/copper(II) catalytic cycle. The radical, enantioselective catalytic Reformatsky reaction mediated by Me₂Zn can be efficiently promoted by copper(I) complexes avoiding the use of other promoters such as air and oxidant, giving more reproducible and affordable conditions. The CuCN-mediated enantioselective addition of ethyliodoacetate to functionalized ketones is described in this paper.     

Synthesis of glucose-tagged triazolium ionic liquids and their application as solvent and ligand for copper(I) catalyzed amination

Glucose-linked 1,2,3-triazolium ionic liquids have been synthesized as a new class of chiral solvents by copper(I) catalyzed regioselective cycloaddition of a glucose azide with a glucose alkyne followed by quaternization with methyl iodide. The tagging of glucose to triazolium core makes these molecules act as reusable ligand and solvent in copper(I) catalyzed amination of aryl halides with aqueous ammonia. While the free hydroxyl groups of sugar help in stabilizing copper(I) species during the reaction thus acting as a ligand, the triazolium salt which makes it a liquid at room temperature serves as a reusable solvent. These chiral ionic liquids derived from low-cost natural sources can find utility in various transition-metal catalyzed reactions, and can be explored for asymmetric synthesis in future.     

Iron(II)/copper(I)-mediated stereoselective carbozincation of ynamides. One-pot synthesis of α-allyl-tetrasubstituted-enamides

The iron(II) chloride- and copper(I) iodide-mediated carbozincation of a panel of substituted ynamides is described in this article. The reaction is totally regio- and stereoselective. Experiments showed that the reaction mediated with Fe(II) was more substrate dependent than the reaction performed with Cu(I). Interestingly, in the presence of allylbromide, stereoselective carboallylation can be achieved for the first time in a one-pot procedure, leading to skipped dienamides.     

Reversible binding of dioxygen by the copper(I) complex with tris(2-dimethylaminoethyl)amine (Me6tren) ligand

At low temperatures, the mononuclear copper(I) complex of the tetradentate tripodal aliphatic amine Me(6)tren (Me(6)tren = tris(2-dimethylaminoethyl)amine) [Cu(I)(Me(6)tren)(RCN)](+) first reversibly binds dioxygen to form a 1:1 Cu-O(2) species which further reacts reversibly with a second [Cu(I)(Me(6)tren)(RCN)](+) ion to form the dinuclear 2:1 Cu(2)O(2) adduct. The reaction can be observed using low temperature stopped-flow techniques. The copper superoxo complex as well as the peroxo complex were characterized by resonance Raman spectroscopy. The spectral characteristics and full kinetic and thermodynamic results for the reaction of [Cu(I)(Me(6)tren)(RCN)](+) with dioxygen are reported.     

Synthesis of Interlocked Diazacoronand System

Abstract

New 2,9-disubstituted 1,10-phenanthroline derivatives have been obtained, retaining the ability to form stable complexes with transition metals. Due to special, pseudotetrahedral topography of the copper(I) complexes the subsequent ring formation reaction can lead to copper(I) catenates. Thus, the known 2,9-bis(p-hydroxyphenyl)-1,10-phenanthroline ligand, was elongated by the reaction with tert-butyl bromoacetate, forming a diester capable of undergoing a double amidation reaction. Such synthetic strategy can provide the corresponding diazacoronands as well as amide-containing interlocked catenane systems, when a three-dimensional template effect of copper atom is employed.     

Modulating catalytic activity of polymer‐based cuAAC “click” reactions

The copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) reaction is used to synthesize complex polymer architectures. In this work, we demonstrate the control of this reaction at 25 °C between polystyrene (PSTY) chains through modulating the catalytic activity by varying the combinations of copper source (i.e., Cu(I)Br or copper wire), ligand (PMDETA and/or triazole ligand), and solvent (toluene or DMF). The fastest rate of CuAAC was found using Cu(I)Br/PMDETA ligand in toluene, reaching near full conversion after 15 min at 25 °C. For the same catalysts system, DMF also gave fast rates of “click” (95% conversion in 25 min). Cu(0) wire in toluene gave a conversion of 98% after 600 min, a much higher rate than that observed for the same catalyst system used in DMF. When the PSTY had a chemically bound triazole ring close to the site of reaction, the rate of CuAAC in toluene increased significantly, 97% in 180 min at 25 °C, in agreement with our previously published results. This suggests that rapid rates can be obtained using copper wire and will have direct applications to the synthesis of compound where air, removal of copper, and reuse of the copper catalyst are required. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Copper(I)-catalyzed synthesis of 2,5-disubstituted furans and thiophenes from haloalkynes or 1,3-diynes

A regioselective synthesis of 2,5-disubstituted furans using copper(I) catalyst from haloalkynes in a one-pot procedure has been reported. This chemistry proceeds through the hydration reaction of 1,3-diynes, which can be readily prepared from the coupling reaction of haloalkynes in the presence of CuI. The procedure also can be used for the facile synthesis of 2,5-disubstituted thiophenes.     

Practical one-pot synthesis of 5-alkynyl-1,2,3-triazoles via heterogeneous copper(I)-catalyzed tandem three-component click/alkynylation reaction

An efficient and practical route to 5-alkynyl-1,2,3-triazoles has been developed via heterogeneous tandem CuAAC/alkynylation reaction of organic azides, alkynes and 1-bromoalkynes by using an L-proline-functionalized MCM-41-anchored copper(I) complex [L-Proline-MCM-41-CuCl] as catalyst under mild conditions. The reaction produces a wide variety of 5-alkynyl-1,2,3-triazoles in mostly good to excellent yields. The new immobilized copper(I) complex can be readily prepared from commercially available and inexpensive reagents and displays the same catalytic activity as CuCl. The L-Proline-MCM-41-CuCl catalyst is also easy to recover via a simple filtration process and can be reused at least seven times without apparent loss of activity.     

Reaction of arylthallium (III) compounds with Copper (II) and (I) cyanides. Synthesis of aryl cyanide

Various kinds of arylthallium(III) salts react with copper (II) or (I) cyanide in acetonitrile or pyridine to give the corresponding aryl cyanides in good yield. In acrylonitrile the reaction using copper(I) cyanide was revealed to be of an ionic concerted intermolecular and not radical type.     

Functional monomers and polymers. XXXV. Oxidation of hydroquinone catalyzed by Cu(II)–polyelectrolyte complexes

Oxidation of hydroquinone catalyzed by copper(II) complexes of poly-1-vinylimidazole, vinylamine-vinylacetamide copolymer, and polyethyleneimine was studied in aqueous solution at 25°C. The rate of oxidation was determined spectrophotometrically over several pH values. The rate of copper(II) reduction was evaluated from copper(I)–cuproin complex formation, and the reoxidation of copper(I) to copper(II) was observed by visible spectroscopy. Among the copper(II) complexes, poly-1-vinylimidazole complex exhibited excellent catalytic activity, which amounted to over 20 times that of aqueous copper(II) ion solution, while the reduction of copper(II) in the former system was slower than that in the latter system. The reoxidation of copper(I) to copper(II) was found to be completed immediately in the presence of polymer ligands such as poly-1-vinylimidazole, while copper(I) ion was only slowly reoxidized. The discussion of the reaction mechanism emphasizes the importance of the reoxidation process.     

Efficient synthesis of 2-substituted-1,2,3-triazoles

In this three-component reaction, alkynes undergo a copper(I)-catalyzed cycloaddition with sodium azide and formaldehyde to yield 2-hydroxymethyl-2 H-1,2,3-triazoles, which are useful intermediates that can be readily converted to polyfunctional molecules. The hydroxymethyl group can also be removed, providing convenient access to N H-1,2,3-triazoles. The reaction is experimentally simple and readily scalable.     

Controlled anodic generation of the catalyst in kinetic continuous flow analysis

Controlled anodic dissolution of copper in a separate generator cell yields well-defined concentrations of catalyst, depending on the voltage applied. This adjustable generation of copper catalyst makes it possible to determine iron over a wide range of concentration (10–1500 μg Fe³⁺ ml^-1) via the iron(III)—thiosulphate reaction. By the copper(II)-catalyzed hydrogen peroxide—hydroquinone reaction, EDTA can be determined as an inhibitor (0.5–5 μg ml^-1) and cadmium(II) as a reactivator (1–10 μg ml^-1). As zinc(II) forms complexes with 2,2'-bipyridine, which activates copper in this reaction, it can be determined (5–50 μg Zn²⁺ ml^-1) by measuring the decrease in activation. The electrogeneration of silver ion as a catalyst is also described. The sulphanilic acid—peroxodisulphate reaction is catalyzed by silver(I), which is again activated by 2,2'-bipyridine. Zinc(II) can be determined (0.29–2.9 mg Zn²⁺ ml^-1) by the same principle as in the copper(II)-catalyzed reaction.     

Exceptional affinity of nanostructured organic-inorganic hybrid materials towards dioxygen: confinement effect of copper complexes

We report the exceptional reactivity towards dioxygen of a nanostructured organic-inorganic hybrid material due to the confinement of copper cyclam within a silica matrix. The key step is the metalation reaction of the ligand, which can occur before or after xerogel formation through the sol-gel process. The incorporation of a Cu(II) center into the material after xerogel formation leads to a bridged Cu(I)/Cu(II) mixed-valence dinuclear species. This complex exhibits a very high affinity towards dioxygen, attributable to auto-organization of the active species in the solid. The remarkable properties of these copper complexes in the silica matrix demonstrate a high cooperative effect for O(2) adsorption; this is induced by close confinement of the two copper ions leading to end-on mu-eta(1):eta(1)-peroxodicopper(II) complexes. The anisotropic packing of the tetraazamacrocycle in a lamellar structure induces an exceptional reactivity of these copper complexes. We show for the first time that the organic-inorganic environment of copper complexes in a silica matrix fully model the protecting role of protein in metalloenzymes. For the first time an oxygenated dicopper(II) complex can be isolated in a stable form at room temperature, and the reduced Cu(2) (I,I) species can be regenerated after several adsorption-desorption cycles. These data also demonstrate that the coordination scheme and reactivity of the copper cyclams within the solid are quite different from that observed in solution.     

Stabilisation of copper(II) tertiary-phosphine or -arsine complexes—II. Role of inductive effect and reaction conditions in stabilising copper(II)-arsine complexes of hybrid oxygen-arsenic ligands from o-R2AsC6H4CO2H

The characterization of the products of reactions between anhydrous/hydrated copper(II) acetate and the title acids having R = Me, C₆H₁₁, Ph and p-tolyl in different solvents and at different temperatures with the help of elemental analysis, TGA, DTA, room temperature magnetic susceptibility, IR, and UV-VIS and EPR spectral data reveal that a competition exists between the chelation of arsine to copper(II) on one side and the reduction of copper(II) to copper(I) and the subsequent chelation of the arsine to copper(I) and/or that of the arsine oxide to copper(II) on the other. This competition which is expected to be normally governed by the inductive effect of group R is disturbed by the change in reaction conditions leading to the conclusion that the reaction conditions rather than the inductive effect of the group R control the mode of reaction.