Direct catalytic asymmetric mannich reactions of malonates and beta-keto esters

The first catalytic asymmetric direct Mannich reaction of malonates and beta-keto esters has been developed. Malonates react with an activated N-tosyl-alpha-imino ester catalyzed by chiral tert-butyl-bisoxazoline/Cu(OTf)(2) to give the Mannich adducts in high yields and with up to 96% ee. These reactions create a chiral quaternary carbon center and it is demonstrated that this new direct Mannich reactions provides for example a new synthetic procedure for the formation of optically active beta-carboxylic ester alpha-amino acid derivatives. A series of different beta-keto esters with various ester substituents has been screened as substrates for the catalytic asymmetric direct Mannich reaction and it was found that the best results in terms of yield, diastereo- and enantioselectivity were obtained when tert-butyl esters of beta-keto esters were used as the substrate. The reaction of different beta-keto tert-butyl esters with the N-tosyl-alpha-imino ester gave the Mannich adducts in high yields, diastereo- and enantioselectivities (up to 95% ee) in the presence of chiral tert-butyl-bisoxazoline/Cu(OTf)(2) as the catalyst. To expand the synthetic utility of this direct Mannich reaction a diastereoselective decarboxylation reaction was developed for the Mannich adducts leading to a new synthetic approach to attractive optically active beta-keto alpha-amino acid derivatives. Based on the stereochemical outcome of the reactions, various approaches of the N-tosyl-alpha-imino ester to the chiral bisoxazoline/Cu(II)-substrate intermediate are discussed.     

Borondipyrromethene-derived Cu2+ sensing chemodosimeter for fast and selective detection

Here, we report a new Cu(2+)-selective fluorescent turn-on probe BODIPY-EP, in which the 2-pyridinecarboxylic acid is connected to a 6-hydroxyindole-based BODIPY platform through an ester linkage. The ester bond of BODIPY-EP is selectively hydrolyzed by the reaction with Cu(2+) under mild and neutral conditions to generate BODIPY-OH, showing strong characteristic fluorescence of BODIPY-OH. The favorable features of BODIPY-EP towards Cu(2+) include fast response, large fluorescence enhancement and high selectivity. We further demonstrated that the membrane-permeable probe reacts with intracellular Cu(2+) and exhibits bright fluorescence in living cells.     

Transition metal ion-assisted photochemical generation of alkyl halides and hydrocarbons from carboxylic acids

Near-UV photolysis of aqueous solutions of propionic acid and aqueous Fe(3+) in the absence of oxygen generates a mixture of hydrocarbons (ethane, ethylene and butane), carbon dioxide, and Fe(2+). The reaction becomes mildly catalytic (about five turnovers) in the presence of oxygen which converts a portion of alkyl radicals to oxidizing intermediates that reoxidize Fe(2+). The photochemistry in the presence of halide ions (X(-) = Cl(-), Br(-)) generates ethyl halides via halogen atom abstraction from FeX(n)(3-n) by ethyl radicals. Near-quantitative yields of C(2)H(5)X are obtained at ≥0.05 M X(-). Competition experiments with Co(NH(3))(5)Br(2+) provided kinetic data for the reaction of ethyl radicals with FeCl(2+) (k = (4.0 ± 0.5) × 10(6) M(-1) s(-1)) and with FeBr(2+) (k = (3.0 ± 0.5) × 10(7) M(-1) s(-1)). Photochemical decarboxylation of propionic acid in the presence of Cu(2+) generates ethylene and Cu(+). Longer-chain acids also yield alpha olefins as exclusive products. These reactions become catalytic under constant purge with oxygen which plays a dual role. It reoxidizes Cu(+) to Cu(2+), and removes gaseous olefins to prevent accumulation of Cu(+)(olefin) complexes and depletion of Cu(2+). The results underscore the profound effect that the choice of metal ions, the medium, and reaction conditions exert on the photochemistry of carboxylic acids.     

Catalytic Enantioselective Benzilic Ester Rearrangement

We report the first examples of catalytic enantioselective benzilic ester rearrangement reaction. In the presence of a catalytic amount of Cu(OTf)₂ and a chiral box ligand under mild conditions, reaction of 2,3‐diketoesters with alcohols afforded structurally diverse α‐aryl(alkyl) substituted‐α‐hydroxy malonates (tartronic esters) in good to excellent yields with high enantioselectivities. Preliminary mechanistic studies indicated that hemiketalization, rather than the dynamic kinetic resolution of hemiketal, was the enantiodetermining step under our reaction conditions.     

Kinetic determination of ultramicro amounts of copper

A new catalytic reaction is proposed and a kinetic method developed for the determination of ultramicro amounts of Cu(II) on the basis of its catalytic activity in oxidation of the 2-thiosemicarbazone of sodium 1,2-naphthoquinone-4-sulphonate by hydrogen peroxide in the presence of ascorbic acid. Under optimal conditions the sensitivity of the method is 0.25 ng/ml. The relative error is 4.8-18.2% for the concentration range 5-0.8 ng/ml. Most foreign ions do not change the rate of the catalysed reaction. Co(2+) and I(-) catalyse the reaction, Ni(2+) extensively inhibits it, and in the presence of EDTA only the uncatalysed reaction takes place.     

A new paradigm for carbon-carbon bond formation: aerobic, copper-templated cross-coupling

Thiol esters and boronic acids react to produce ketones under aerobic conditions in the presence of catalytic quantities of a CuI or CuII salt. The reaction occurs at reasonable rates between room temperature and 50 degrees C at neutral pH using thiol esters derived from bulky 2 degrees amides of thiosalicylamides such as those based on N-tert-butyl-2-mercaptobenzamide. In this mechanistically unprecedented reaction system, the carbon-carbon bond formation occurs through templating of the thiol ester and the boronic acid at copper; the system is rendered catalytic in copper under the aerobic conditions.     

Catalytic asymmetric Mannich reactions of glycine derivatives with imines. A new approach to optically active alpha,beta-diamino acid derivatives

Imines of glycine alkyl esters react with imines in a diastereo- and highly enantioselective Mannich reaction in the presence of chiral copper(I) complexes as the catalyst to give optically active alpha,beta-diamino acid derivatives. A series of imines of glycine esters derived from glycine and aromatic carbonyl compounds has been screened as substrates for the Mannich reaction with different imines in the presence of various combinations of metal salts and chiral ligands. The benzophenone imine of glycine esters was found to react with N-protected imines in a diastereoselective fashion giving functionalized alpha,beta-diamino acid esters with excellent enantioselectivities. The most effective chiral catalysts are chiral copper(I) complexes having phosphino-oxazoline (P,N)-ligands, and among these ligands, those derived from (1R,2S)-dihydroxy-1,2,3,4-tetrahydronaphthalene gave the best results. The scope of this new catalytic asymmetric reaction of the benzophenone imine glycine esters is demonstrated for the reaction with different N-protected-C-aryl and C-alkyl imines giving the Mannich adducts with excellent optical purity. Furthermore, the synthetic aspects of the reaction are presented by converting the Mannich adducts into alpha,beta-diamino acid derivatives. The relative and absolute configuration of the Mannich adduct have been determined and based on the stereochemical outcome of the reaction a tetrahedral chiral-copper(I)-imino glycine alkyl ester intermediate is proposed. In this intermediate the Re-face of the benzophenone imine glycine ester is shielded by the chiral ligand leaving the Si-face available for approach of the Si-face of the imine. A series of semiempirical calculations has been performed to support the structure of the tetrahedral chiral-copper(I) complex and to account for the influence of the substituents in the chiral phosphino-oxazoline ligands.     

Synthesis of gallic acid: Cu(2+)-mediated oxidation of 3-dehydroshikimic acid

With the elaboration of high-yielding, high-titer syntheses of 3-dehydroshikimic acid from glucose using recombinant Escherichia coli, oxidation of this hydroaromatic becomes a potential route for synthesis of gallic acid. Conversion of 3-dehydroshikimic acid into gallic acid likely proceeds via initial enolization of an alpha-hydroxycarbonyl and oxidation of the resulting enediol. 3-Dehydroshikimate enolization in water was catalyzed by inorganic phosphate while Zn(2+) was used to catalyze enolization in acetic acid. Enediol oxidation employed Cu(2+) as either the stoichiometric oxidant or as a catalyst in the presence of a cooxidant. Gallic acid was produced in a yield of 36% when 3-dehydroshikimic acid in phosphate-buffered water reacted for 35 h with H2O2 and catalytic amounts of CuSO(4). 3-Dehydroshikimate-containing, phosphate-buffered culture supernatants reacted with stoichiometric amounts of CuCO(3)Cu(OH)(2) and Cu(x)(H(3-x)(PO4)(2) to give gallic acid in yields of 51% in 5 h and 43% in 12 h, respectively. Solutions of 3-dehydroshikimic acid in acetic acid reacted with stoichiometric amounts of Cu(OAc)(2) to afford a 74% yield of gallic acid in 36 h. Acetic acid solutions of 3-dehydroshikimic acid could also be oxidized by air using catalytic quantities of Cu(OAc)(2). ZnO accelerated these oxidations leading to a 67% yield of gallic acid in 4 h when an acetic acid solution of 3-dehydroshikimic acid was reacted with O(2) and a catalytic amount of Cu(OAc)(2).     

（R）—N—乙酰四氢噻唑—2—硫酮—4—羧酸与醇的反应

（Ｒ）－Ｎ－乙酰四氢噻唑－２－硫酮－４－羧酸与醇反应，在ＳＯＣｌ２存在下得到乙酸酯及四氢噻唑－２－硫酮－４－羧酸酯；在碳酸钾存在下得到乙酸酯及四氢噻唑－２－硫酮－４－羧酸；在二环己基碳二亚胺（ＤＣＣ）存在下得到缩水产物Ｎ－乙酰四氢噻唑－２－硫酮－４－羧酸酯。     

An effective new synthesis of 4-aminopyrrole-2-carboxylates

[reaction: see text] A series of 4-amino-1H-pyrrole-2-carboxylic acid benzyl esters has been synthesized in 61-84% yields on treatment of N-PhF-4-oxoproline benzyl ester and its 3-alkyl-substituted derivatives with different primary and secondary amines and a catalytic amount of TsOH in THF. 4-Hydroxy-1H-pyrrole-2-carboxylic acid benzyl esters were prepared in 59 and 70% yields by treatment of N-PhF-4-oxoproline benzyl esters with ammonium hydroxide in THF.     

Structure and catalytic properties of magnesia-supported copper salts of molybdovanadophosphoric acid

The structure and stability of magnesia-supported copper salts of molybdovanadophosphoric acid (Cu(2)PMo(11)VO(40)) were characterized by different techniques. The catalyst was prepared in ethanol by impregnation because this solvent does not hurt texture of the water-sensitive MgO and Cu(2)PMo(11)VO(40). The Keggin-type structure compound may be degraded partially to form oligomerized polyoxometalate when supported on MgO. However, the oligomers can rebuild as the Keggin structure again after thermal treatment in air or during the reaction. Meanwhile, the V atoms migrate out of the Keggin structure to form a lacunary structure, as observed by Fourier transform IR spectroscopy. Moreover, the presence of Cu(2+) as a countercation showed an affirmative influence on the migration of V atoms, and the active sites derived from the lacunary species generated after release of V from the Keggin anion. The electron paramagnetic resonance data imply that V(5+) autoreduces to V(4+) in the fresh catalyst, and during the catalytic reaction a large number of V(4+) ions are produced, which enhance the formation of O(2-) vacancies around the metal atoms. These oxygen vacancies may also improve the reoxidation function of the catalyst. This behavior is correlated to higher catalytic properties of this catalyst. The oxidative dehydrogenation of hexanol to hexanal was studied over this catalyst. After reaction at 553.2 K for 50 h, catalytic properties did not decrease and exhibited higher selectivity (>96.0%) toward hexanal.     

Monomeric metal aqua complexes in the interlayer space of montmorillonites as strong Lewis acid catalysts for heterogeneous carbon-carbon bond-forming reactions

Montmorillonite-enwrapped copper and scandium catalysts (Cu(2+)- and Sc(3+)-monts) were easily prepared by treating Na(+)-mont with the aqueous solution of the copper nitrate and scandium triflate, respectively. The resulting Cu(2+)- and Sc(3+)-monts showed outstanding catalytic activities for a variety of carbon-carbon bond-forming reactions, such as the Michael reaction, the Sakurai-Hosomi allylation, and the Diels-Alder reaction, under solvent-free or aqueous conditions. The remarkable activity of the mont catalysts is attributable to the negatively charged silicate layers that are capable of stabilizing metal cations. Furthermore, these catalysts were reusable without any appreciable loss in activity and selectivity. The Cu(2+)-mont-catalyzed Michael reaction proceeds via a ternary complex in which both the 1,3-dicarbonyl compound and the enone are coordinated to a Lewis acid Cu(2+) center.     

Synthesis of derivatives of 2-amino-3-ethoxycarbonylthiophene

A number of alkylidene esters are synthesized from the corresponding ketones and cyanoacetic ester, and treatment of the esters with sulfur in the presence of a catalytic amount of diethylamine gives 2-amino-3-ethoxycarbonylthiophene derivatives.     

Factors that control catalytic two- versus four-electron reduction of dioxygen by copper complexes

The selective two-electron reduction of O(2) by one-electron reductants such as decamethylferrocene (Fc*) and octamethylferrocene (Me(8)Fc) is efficiently catalyzed by a binuclear Cu(II) complex [Cu(II)(2)(LO)(OH)](2+) (D1) {LO is a binucleating ligand with copper-bridging phenolate moiety} in the presence of trifluoroacetic acid (HOTF) in acetone. The protonation of the hydroxide group of [Cu(II)(2)(LO)(OH)](2+) with HOTF to produce [Cu(II)(2)(LO)(OTF)](2+) (D1-OTF) makes it possible for this to be reduced by 2 equiv of Fc* via a two-step electron-transfer sequence. Reactions of the fully reduced complex [Cu(I)(2)(LO)](+) (D3) with O(2) in the presence of HOTF led to the low-temperature detection of the absorption spectra due to the peroxo complex [Cu(II)(2)(LO)(OO)] (D) and the protonated hydroperoxo complex [Cu(II)(2)(LO)(OOH)](2+) (D4). No further Fc* reduction of D4 occurs, and it is instead further protonated by HOTF to yield H(2)O(2) accompanied by regeneration of [Cu(II)(2)(LO)(OTF)](2+) (D1-OTF), thus completing the catalytic cycle for the two-electron reduction of O(2) by Fc*. Kinetic studies on the formation of Fc*(+) under catalytic conditions as well as for separate examination of the electron transfer from Fc* to D1-OTF reveal there are two important reaction pathways operating. One is a rate-determining second reduction of D1-OTF, thus electron transfer from Fc* to a mixed-valent intermediate [Cu(II)Cu(I)(LO)](2+) (D2), which leads to [Cu(I)(2)(LO)](+) that is coupled with O(2) binding to produce [Cu(II)(2)(LO)(OO)](+) (D). The other involves direct reaction of O(2) with the mixed-valent compound D2 followed by rapid Fc* reduction of a putative superoxo-dicopper(II) species thus formed, producing D.     

Isolated Cu2+ ions: active sites for selective catalytic reduction of NO

Cu chabazite catalysts show remarkable low temperature activity in selective catalytic reduction (SCR) of NO. This high activity is due to the unique character of the zeolite framework that allows only the presence of one type of isolated mononuclear Cu(2+) species. These Cu(2+) species are the active sites for SCR.     

Synthesis of derivatives of 2-amino-3-ethoxycarbonylthiophene

A number of alkylidene esters are synthesized from the corresponding ketones and cyanoacetic ester, and treatment of the esters with sulfur in the presence of a catalytic amount of diethylamine gives 2-amino-3-ethoxycarbonylthiophene derivatives.     

Catalytic method of synthesis of phosphorus acids esters from zinc phosphide and alcohol

Ecologically safe effective catalytic method for preparing phosphorous and phosphoric acid esters by oxidation of zinc phosphide with oxygen in the solution of copper(II) halides in butanol at 50–70°C is developed. It is found that in the presence of Cu(II) chloride a mixture of dibutyl hydrogen phosphite and tributyl phosphate is formed, while at the catalysis with Cu(II) bromide tributyl phosphate is mainly obtained. Promoting action of hydrogen chloride on the reaction rate and yield of organophosphorus compounds is established. Optimal reaction conditions are found and redox mechanism of catalytic process is assumed.     

Quantitative analysis of multiple urinary biomarkers of carcinoid tumors through gold-nanoparticle-assisted laser desorption/ionization time-of-flight mass spectrometry

A highly selective and sensitive coumarin-based chemodosimeter 1 for Cu(2+) in water is reported in this work. 1 was designed and facilely synthesized by a one-step reaction with coumarin as a fluorophore and 2-picolinic acid as the binding moiety, which showed very week fluorescence in buffer solution, and its fluorescence was considerably enhanced by the addition of Cu(2+) at room temperature in 5 min. Mechanism study suggested that Cu(2+) promoted the hydrolysis of 1 via the catalytic sensing cycle, generating a highly fluorescent product 7-hydroxycoumarin with fluorescence signal greatly amplified. The probe exhibited remarkably selective fluorescence enhancement to Cu(2+) over other metal ions at 454 nm, with a detection limit of 35 nM Cu(2+). Under optimal condition, 1 was successfully used for the determination of Cu(2+) in fetal equine serum and two water samples.     

Functional mimicry of carboxypeptidase A by a combination of transition state stabilization and a defined orientation of catalytic moieties in molecularly imprinted polymers

An artificial model for the natural enzyme carboxypeptidase A has been constructed by molecular imprinting in synthetic polymers. The tetrahedral transition state analogues (TSAs 4 and 5) for the carbonate hydrolysis have been designed as templates to allow incorporation of the main catalytic elements, an amidinium group and a Zn(2+) or Cu(2+) center, in a defined orientation in the transition state imprinted active site. The complexation of the functional monomer and the template in presence of Cu(2+) through stoichiometric noncovalent interaction was established on the basis of (1)H NMR studies and potentiometric titration. The Cu(2+) center was introduced into the imprinted cavity during polymerization or by substitution of Zn(2+) in Zn(2+) imprinted polymers. The direct introduction displayed obvious advantages in promoting catalytic efficiency. With substrates exhibiting a very similar structure to the template, an extraordinarily high enhancement of the rate of catalyzed to uncatalyzed reaction (k(cat)/k(uncat)) of 10(5)-fold was observed. If two amidinium moieties are introduced in proximity to one Cu(2+) center in the imprinted cavity by complexation of the functional monomer 3 with the template 5, the imprinted catalysts exhibited even higher activities and efficiencies for the carbonate hydrolysis with k(cat)/k(uncat) as high as 410,000. These are by far the highest values obtained for molecularly imprinted catalysts, and they are also considerably higher compared to catalytic antibodies. Our kinetic studies and competitive inhibition experiments with the TSA template showed a clear indication of a very efficient imprinting procedure. In addition, this demonstrates the important role of the transition state stabilization during the catalysis of this reaction.     

Copper(I) iodide-catalysed arylation of acetoacetate to yield 2-arylacetic acid esters

The C-C coupling reaction between ethyl acetoacetate and aryl halides in the presence of CuI is described. The effects of solvent, ligands such as vicinal diamines and amino acids, base and temperature are reported. The arylated acetoacetate ester is deacylated under the reaction conditions resulting in the generation of 2-arylacetic acid esters, constituting a mild alternative to direct arylation of carboxylate esters.