Baeyer—Villiger Oxidation in Supercritical CO2 with Potassium Peroxomonosulfate Supported on Acidic Silica Gel.

Supercritical carbon dioxide (scCO2) is an efficient reaction medium to perform the Baeyer-Villiger oxidation with hydrated silica-supported potassium peroxomonosulfate (h-SiO2.KHSO5) under flow-through conditions. Hydration modulates the reactivity of the active surface by softening the acidity of the KHSO4 present in the supported reagent. The reaction in scCO2 is much more efficient than in n-hexane under similar conditions, which is attributed to better transport and solvating properties of the supercritical medium with regard to n-hexane.

ChemInform Abstract: Palladium-Catalyzed Suzuki Carbonylative Reaction of α-Halomethyl Oxime Ethers: A Regioselective Route to Unsymmetrical 1,3-Oxyiminoketones.

ChemInform Abstract: Switchable Palladium-Catalyst Reaction of Bromomethyl Sulfoxides, CO, and N-Nucleophiles: Aminocarbonylation at Csp3versus Oxidative Carbonylation of Amines.

Pd2(dba)3/ Xantphos-catalyzed coupling of the sulfoxides (I) and (V) with amines and carbon monoxide allows a new and efficient access to amides of type (IV) and (VI).

First synthesis of the chiral mixed O/S ligands, 1,2-sulfinyl thiols: application as chiral proton sources in enantioselective protonations of enolates

Abstract A suitable method for the preparation of the chiral mixed O/S ligands 1,2-sulfinyl thiols is described. These compounds have then been used as a chiral proton source in the enantioselective protonation of 2-methyl tetralone enolate and the results are compared with those obtained from the analogous alcohols. A theoretical model is proposed to explain the different behaviors exhibited in the protonation reaction for each of these proton sources. Configurational assignments for the new chiral thiols have been carried out by means of X-ray analysis.

ChemInform Abstract: Modified Photobehavior of Carboxylic Acid Derivatives Induced by Protonation.

Abstract A series of carboxylic acid derivatives 1–6 containing a second interacting function have been converted into the corresponding O -protonated species or acylium ions upon treatment with 96% sulfuric acid or oleum, respectively, at room temperature. The resulting stable cations have been spectroscopically characterized and submitted to irradiation. Cis-trans photoisomerization was observed in the ionic speciesderived from trans -crotonic, fumaric and maleic acids, and maleic anhydride. By contrast protonated crotonolactone 5a+ was found to be photostable. Finally, protonated α-bromobutyrolactone 6a+ was clean and efficiently dehydrohalogenated to 5a+ upon irradiation. Since the norm…

Cover Picture: Measuring the Relative Reactivity of the Carbon–Hydrogen Bonds of Alkanes as Nucleophiles (Angew. Chem. Int. Ed. 42/2018)

Reactions at Interfaces: Oxygenation of n-Butyl Ligands Anchored on Silica Surfaces with Methyl(trifluoromethyl)dioxirane

The oxygenation of n-butyl and n-butoxy chains bonded to silica with methyl(trifluoromethyl)dioxirane (1) revealed the ability of the silica matrix to release electron density toward the reacting C(2)-H σ-bond through the Si-C(1) and Si-O(1) σ-bonds connecting the alkyl chain to the surface (silicon β-effect). The silica surface impedes neither the alkyl chain adopting the conformation required for the silicon β-effect nor dioxirane 1 approaching the reactive C(2) methylene group. Reaction regioselectivity is insensitive to changes in the solvation of the reacting system, the location of organic ligands on the silica surface, and the H-bonding character of the silica surface. Reaction rates…

Unprecedented Palladium-Catalyzed Cross-Coupling Reaction of α-Bromo Sulfoxides with Boronic Acids

[reaction: see text] A new Suzuki-type palladium-catalyzed reaction of boronic acids with alpha-bromo sulfoxides has been developed using a protocol similar to the well-documented reaction of boronic acids with aryl halides. Both cross-coupling and homocoupling processes were observed. The best yields in cross-coupling products were obtained when the presence of oxygen was carefully excluded using degassed solvents. The oxidative addition palladium complex intermediate could be isolated and characterized by X-ray single-crystal diffraction.

Gold(I)-Catalyzed Intermolecular Cycloaddition of Allenamides with α,β-Unsaturated Hydrazones: Efficient Access to Highly Substituted Cyclobutanes

α,β-Unsaturated N,N-dialkyl hydrazones undergo a mild [2 + 2] cycloaddition to allenamides when treated with a suitable gold catalyst. The method, which represents the first application of N,N-dialkyl hydrazones in gold catalysis, is compatible with a wide variety of substituents at the alkenyl moiety of the hydrazone component, proceeds with excellent levels of regio- and diastereoselectivity, and provides densely substituted cyclobutanes with good to excellent yields.

Epoxidation of Olefins with a Silica-Supported Peracid in Supercritical Carbon Dioxide under Flow Conditions

Anhydrous 2-percarboxyethyl-functionalized silica (2b), a recyclable supported peracid, is a suitable reagent to perform the epoxidation of alkenes 1 in supercritical carbon dioxide at 250 bar and 40 °C under flow conditions. This procedure simplifies the isolation of the reaction products and uses only carbon dioxide as a solvent under mild conditions. The solid reagent 2b can be easily recycled by a reaction with 30% hydrogen peroxide in an acid medium.

Aryl radicals by copper(II) oxidation of hydrazines: A new method for the oxidative and reductive arylation of alkenes

Abstract A new source of aryl radicals interesting from the preparative point of view has been found in the reaction of arylhydrazines and copper(II) sulfate. The process allows selectively both the reductive and oxidative arylation of alkenes.

Catalytic Functionalization of Methane and Light Alkanes in Supercritical Carbon Dioxide

International audience; The development of catalytic methods for the effective functionalization of methane yet remains a challenge. The best system known to date is the so-called Catalytica Process based on the use of platinum catalysts to convert methane into methyl bisulfate with a TOF rate of 10−3 s. In this contribution, we report a series of silver complexes containing perfluorinated tris(indazolyl)borate ligands that catalyze the functionalization of methane into ethyl propionate upon reaction with ethyl diazoacetate (EDA) by using supercritical carbon dioxide (scCO2) as the reaction medium. The employment of this reaction medium has also allowed the functionalization of ethane, prop…

ChemInform Abstract: Selective “One-Pot” Synthesis of Functionalized Cyclopentenones.

Reaction of squaric acid derivatives with vinyl magnesium bromide followed by treatment with trifluoroethanol allows a new and stereoselective access to functionalized cyclopentenones of type (III)/ (V).

Silica-Immobilized NHC-Gold(I) Complexes: Versatile Catalysts for the Functionalization of Alkynes under Batch and Continuous Flow Conditions

Immobilized sterically demanding NHC-Au(I) complexes silica-[(IPrR)Au]Cl and silica-[(IAdPrR)Au]Cl are synthesized and characterized. These complexes are suitable catalysts in typical homogeneous Au(I)-catalyzed alkyne reactions such as hydration, hydroamination, hydroarylation, or cycloisomerization. The results obtained with the immobilized catalysts in reactions in batch are comparable to those obtained with their homogeneous counterparts with the advantage of easily recovered and recycled in successive reactions. Their catalytic activity decreases when reused in batch reactions, probably because of crushing that is associated with magnetic stirring. In contrast, these immobilized cataly…

Direct observation and thermal transformations of dications derived from dibenzotropylium ions

Abstract Carboxylic acid 1 and its derivatives 2 , 3 treated with triflic acid below −20°C afford the dications 1H 2+2- 3H 2+2. Cyclodehydration above 20°C (or in the gas-phase, CIMS of 3 ) leads to the diprotonated ketone 4H 2+2.

ChemInform Abstract: Gold(I)-Catalyzed Reactions of 1-(ortho-Alkynylaryl)ureas: Highly Selective Heterocyclization and Synthesis of Mixed N,O-Acetals.

Treatment of alkynylureas (I) with trifluoroethanol in the presence of a Au/Ag catalytic system provides N-6-exo-dig heterocyclization products (III) and in some cases open chain acetals as side products.

Synthesis of chiral β-disulfoxides and their racemization with strong bases

Abstract β-Disulfoxides can be obtained from different α-sulfunylcarbanions and sulfinates. While α-unsubstituted and monosubstituted β-disulfoxides are configurationally stable in the presence of strong bases, α,α-disubstituted β-disulfoxides epimerize through an intermolecular mechanism.

Competition between decarboxylation and isomerization in the C3H5O 2+ energy surface. Justification of the experimental results by molecular orbital calculations on the solvated ions

In constrast with recent molecular orbital calculations on the decarboxylation of O-protonated 2-oxetanone, this experimental work indicates that no decarboxylation of this cation occurs in sulphuric acid solution up to 150°C, but instead a clean isomerization to protonated acrylic acid takes place. Parallel theoretical work shows that the gas-phase model is too crude to account successfully for the experimental facts obtained in acidic media. However, the latter are well reproduced when the effect of the solvent is taken into account. The present findings do not necessarily invalidate the reaction mechanism currently accepted to explain the rate enhancement and change of stereochemistry ac…

Chemical and spectroscopical evidence for an electron‐transfer mechanism in the reaction of arenesulfonyl chlorides with anions

The reaction of amide and amidate anions 2 with p-toluenesulfonyl chloride (1) under different reaction conditions gives rise to the total or partial reduction of the acyl halide to p-toluenesulfinic acid (5) and acylation compounds in variable amounts depending on the crowding at the anionic center. This indicates that a Single-Electron Transfer (SET) mechanism is involved in the reactions of 1 with anions. Unpaired electron species are detected by ESR in the course of the reactions.

Supercritical Carbon Dioxide: A Promoter of Carbon-Halogen Bond Heterolysis

as the leaving groupdeparts from the carbon atom prior to the entrance of thenucleophile. Polar protic solvents with high dielectric con-stants promote polar bond heterolysis by providing effectiveH-bonding and electron-pair donation interactions to theleaving group and the incipient carbocation, respectively.Then, the solvent captures the carbocation intermediate togive the corresponding S

A new and versatile method for iodofunctionalization of 1,3-dienes

Abstract We wish to report the reactions of conjugated dienes with I(py) 2 BF 4 . This simple and general method allows the regiospecific 1,2-addition of iodine and a nucleophile to terminal dienes and the 1,4-addition to internal dienes.

ChemInform Abstract: 1,4-Regioselective Iodofunctionalizations of 1,3-Butadiene.

1,3-Butadiene (I) is treated with a iodonium tetrafluoroborate in the presence of HBF4 and aqueous acetonitrile (II) or benzene (IV), yielding the 1,4-adducts (III) or (V).

ChemInform Abstract: Preparation of N,O-Aminals as Synthetic Equivalents of H2C=NAr and (H2C=NHAr)+ Ions: Neutral- and Acid-Promoted Transformations.

A general method for the synthesis of N,O-aminals derived from primary aromatic amines is described. The reactivity of these compounds under neutral and acidic conditions has been studied and the title compounds can be envisaged as general purpose H2CNAr or (H2CNHAr)+ equivalents. N,O-Aminals have been converted into perhydrotriazines by moderate heating and into bis(4-aminoaryl)methane derivatives or N-benzylarylamines, respectively when heated in acidic media with pH control. Reduction of N,O-acetals with sodium cyanoborohydride has revealed that the C–O bond is broken exclusively in acidic media.

Synthesis of an enantiopure 2-arylcyclohexanols from prochiral enol acetates by an enantioselective protonation/diastereoselective reduction sequence

Abstract The enantioselective protonation with 2-sulfinyl alcohols of lithium enolates of 2-arylcyclohexanones with different substituents on the phenyl group takes place with excellent enantioselectivities (89–99%). Chiral 2-phenylcyclohexanone and 2-arylcyclohexanones carrying electron donor substituents on the aromatic ring are converted into the corresponding trans -2-arylcyclohexanols by diastereoselective reduction with sodium naphthalenide in the presence of acetamide. The stereochemical integrity of the tertiary stereocenter is fully preserved using this reduction procedure. Interestingly, the chiral proton source is not consumed in the synthesis.

1,4-regioselective iodofunctionalizations of 1,3-butadiene

Abstract Addition reactions of benzene and acetonitrile to 1,3-butadiene are described. This new iodofunctionalization process proceeds “via” iodonium ion-allylic cation equilibrium and gives regioselectively 1,4-adducts, which can be alternatively obtained by acid treatment of the 1,2-derivative 8 .

Modified photobehavior of carboxylic acid derivatives induced by protonation

Abstract A series of carboxylic acid derivatives 1–6 containing a second interacting function have been converted into the corresponding O -protonated species or acylium ions upon treatment with 96% sulfuric acid or oleum, respectively, at room temperature. The resulting stable cations have been spectroscopically characterized and submitted to irradiation. Cis-trans photoisomerization was observed in the ionic speciesderived from trans -crotonic, fumaric and maleic acids, and maleic anhydride. By contrast protonated crotonolactone 5a+ was found to be photostable. Finally, protonated α-bromobutyrolactone 6a+ was clean and efficiently dehydrohalogenated to 5a+ upon irradiation. Since the norm…

Remarkable effect of lithium bromide in the enantioselective protonation with α-sulfinyl alcohols

Abstract The favourable effect of lithium bromide enhancing the facial enantioselectivity in the protonation of methyl tetralone enolate with α-sulfinyl alcohols is described. Theoretical calculations allow to propose a model to explain the stereochemical course of the protonation reaction.

Gold(I)-catalyzed intermolecular oxyarylation of alkynes: unexpected regiochemistry in the alkylation of arenes.

The reaction between acetylenes and sulfoxides, studied as a test case for gold-catalyzed intermolecular addition, provides the oxyarylation compounds 3 in good yields. Unpredictably, in all cases a single regioisomer arising from the electrophilic aromatic alkylation at the position adjacent to the sulfur atom is obtained instead of the expected Friedel−Crafts regioisomer. A new concerted mechanism based on DFT calculations is proposed to account for the products in this intermolecular gold(I)-catalyzed reaction.

ChemInform Abstract: Oppenauer Oxidation of Secondary Alcohols with 1,1,1-Trifluoroacetone as Hydride Acceptor.

1,1,1-Trifluoroacetone (2a) reacts as a hydride-acceptor in the Oppenauer oxidation of secondary alcohols (1) in the presence of diethylethoxyaluminum. The oxidant allows for selective oxidation of secondary alcohols in the presence of primary alcohols.

Use of Saccharomyces cerevisiae as a whole cell system for aldol condensation in organic medium: Study of the factors affecting the biotransformation

Abstract Saccharomyces cerevisiae has been employed as a whole cell catalyst for a number of asymmetric transformations. This work explores the ability of this microorganism to carry out the asymmetric aldol condensation between 4-nitrobenzaldehyde and acetone. For this purpose, lyophilized cells of the FY86 laboratory strain from stationary phase cultures were employed. This reaction shows stereoselectivity, and its progress is affected by the water concentration in the medium, temperature and the growth stage of the yeast culture. Cell lysis experiments indicate that activity responsible for this biotransformation is located in the soluble fraction.

ChemInform Abstract: A Simple and Efficient Route to 1,4-Diketones from Squaric Acid.

Abstract Squaric acid derivatives react with organolithium compounds at room temperature to afford with excellent yields after hydrolysis, symmetrical and unsymmetrically substituted oxygenated 1,4 diketones bearing alkyl, aryl or heteroaryl groups at the carbonyl positions. In the case of aromatic or heteroaromatic ketones the enol tautomers are also obtained.

Influence of structural factors and enzyme type on the reactivity and enantioselectivity of the enzymatic esterification of bicyclic meso dialcohols

The meso dialcohols 1–7, obtained from the Diels-Alder adducts furan/maleic anhydride, furan/dimethyl acetylenedi-carboxylate, and cyclopentadiene/maleic anhydride, were subjected to enzymatic esterification in organic solvents. A mixture of the corresponding chiral monoacetates and the meso diacetates was obtained. It has been found that reaction rate and enantioselectivity markedly depend on substrate structure, temperature, enzyme type, and nature of the solvent. The presence of an oxygen bridge and an exo configuration are the two structural features which lead to the highest enantioselectivity values.

A Quantitative Model for Alkane Nucleophilicity Based on C−H Bond Structural/Topological Descriptors

A first quantitative model for calculating the nucleophilicity of alkanes is described. A statistical treatment was applied to the analysis of the reactivity of 29 different alkane C−H bonds towards in situ generated metal carbene electrophiles. The correlation of the recently reported experimental reactivity with two different sets of descriptors comprising a total of 86 parameters was studied, resulting in the quantitative descriptor‐based alkane nucleophilicity (QDEAN) model. This model consists of an equation with only six structural/topological descriptors, and reproduces the relative reactivity of the alkane C−H bonds. This reactivity can be calculated from parameters emerging from th…

ChemInform Abstract: First Synthesis of the Chiral Mixed O/S Ligands, 1,2-Sulfinyl Thiols: Application as Chiral Proton Sources in Enantioselective Protonations of Enolates.

Abstract A suitable method for the preparation of the chiral mixed O/S ligands 1,2-sulfinyl thiols is described. These compounds have then been used as a chiral proton source in the enantioselective protonation of 2-methyl tetralone enolate and the results are compared with those obtained from the analogous alcohols. A theoretical model is proposed to explain the different behaviors exhibited in the protonation reaction for each of these proton sources. Configurational assignments for the new chiral thiols have been carried out by means of X-ray analysis.

On the Reactivity of C(sp3)–H σ-Bonds: Oxygenation with Methyl(trifluoromethyl)­dioxirane

The reactivity of C–H σ-bonds of a series of 2-substituted adamantanes 2 towards methyl(trifluoromethyl)dioxirane (1) shows a consistent dependence on the electron-withdrawing ability, either inductive or by resonance, of the substituent. The results are interpreted in terms of the ability of the substrate molecule to delocalize the electronic perturbation of the reacting center at the beginning of the reaction path. The model shows that the electronic demand from the reacting C–H σ-bond is transmitted along the substrate through a chain of hyperconjugative interactions, the relative intensities of which depend on the σ-bonds involved. The substrate molecule simultaneously provides positive…

Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of α-Halomethyl Oxime Ethers and Site-Selective Cross-Coupling of Dihalo Derivatives

The Pd-catalyzed cross-coupling reaction of chloromethyl oxime ethers with a wide range of aryl-, heteroaryl-, and vinylboronic acids proceeds with good yields.

Competitive gold-activation modes in terminal alkynes: an experimental and mechanistic study.

The competition between π- and dual σ,π-gold-activation modes is revealed in the gold(I)-catalyzed heterocyclization of 1-(o-ethynylaryl)urea. A noticeable effect of various ligands in gold complexes on the choice of these activation modes is described. The cationic [Au(IPr)](+) (IPr=2,6-bis(diisopropylphenyl)imidazol-2-ylidene) complex cleanly promotes the π activation of terminal alkynes, whereas [Au(PtBu3 )](+) favors intermediate σ,π species. In this experimental and mechanistic study, which includes kinetic and cross-over experiments, several σ-gold, σ,π-gold, and other gold polynuclear reaction intermediates have been isolated and identified by NMR spectroscopy, X-ray diffraction, or …

First Synthesis of β-Keto Sulfoxides by a Palladium-Catalyzed Carbonylative Suzuki Reaction

[reaction: see text] An unprecedented palladium-catalyzed three-component cross-coupling reaction between alpha-bromo sulfoxide, carbon monoxide, and aromatic boronic acids provides a new and efficient approach to the synthesis of beta-ketosulfoxides. The reaction takes place under mild conditions with a wide range of variously substituted aryl and heteroaryl boronic acids. The carbonylative cross-coupling reaction is strongly favored over competing direct cross-coupling and homocoupling processes, except with boronic acids carrying strong electron-withdrawing substituents.

Switchable palladium-catalyst reaction of bromomethyl sulfoxides, CO, and N-nucleophiles: aminocarbonylation at Csp3 versus oxidative carbonylation of amines.

The palladium-catalyzed reaction of α-bromomethyl sulfoxides, carbon monoxide, and N-nucleophiles follows different reaction pathways according to the catalytic system and the reaction conditions. The Pd-xantphos catalyst affords high yields of α-sulfinyl amides by an aminocarbonylation process and is the first example of this type of transformation for a nonbenzylic sp(3)-hybridized carbon. On the other hand, the oxidative carbonylation of amines occurs with α-bromomethyl sulfoxides, carbon monoxide, and catalytic Pd(PPh(3))(4) under aerobic conditions, yielding ureas and oxalamides from either primary or secondary amines. The reaction with ambident nucleophiles such as amino alcohols was …

Gold(I)-catalysed cascade reactions in the synthesis of 2,3-fused indole derivatives.

A gold(I)-catalysed hydroaminative/arylative cascade for the efficient synthesis of a variety of indole-fused skeletons has been developed. Factors controlling the catalyst loading required in these transformations involving 1,3-unsubstituted indole intermediates have been revealed, allowing isolation of an unprecedented 1,3-dimetallated 3H-indole gold complex characterized by X-ray diffraction.

Palladium-Catalyzed Suzuki Carbonylative Reaction of α-Halomethyl Oxime Ethers: A Regioselective Route to Unsymmetrical 1,3-Oxyiminoketones

Water-Soluble Palladium Nanoparticles: Click Synthesis and Applications as a Recyclable Catalyst in Suzuki Cross-Couplings in Aqueous Media

A new PEG-tagged material, which was prepared by a threefold copper-catalyzed [3+2] cycloaddition (click chemistry), was found to act as an efficient stabilizer for palladium nanoparticles. The newly formed material proved to be active as a recyclable catalyst in Suzuki coupling; the presence of polyether chains allowed for the catalytic runs to be conducted in aqueous media.

Competitive and Selective Csp3Br versus Csp2Br Bond Activation in Palladium-Catalysed Suzuki Cross-Coupling: An Experimental and Theoretical Study of the Role of Phosphine Ligands

Phosphine ligands have been demonstrated to have an effect on reactivity and selectivity in the competitive intramolecular palladium-catalysed Suzuki-Miyaura coupling of dibromo sulfoxide 1a possessing two different hybridised electrophilic carbons. It was found that the bromine bond to the sp(3)-hybridised carbon is selectively replaced in the presence of unhindered phosphines such as PPh(3) or xantphos. The use of hindered phosphine ligands such as P(o-tol)(3) and P(1-naphthyl)(3) reversed the selectivity, conducting the cross-coupling at the Csp(2)-Br. Identical trends were observed in external competition experiments carried out with bromomethyl sulfoxide and different substituted bromo…

Titelbild: Measuring the Relative Reactivity of the Carbon–Hydrogen Bonds of Alkanes as Nucleophiles (Angew. Chem. 42/2018)

Oxidation of alcohols to carbonyl compounds with CrO3.SiO2 in supercritical carbon dioxide.

Supercritical carbon dioxide (scCO2) is an effective reaction medium to perform the oxidation of primary and secondary aliphatic alcohols to the corresponding carbonyl compounds with chromium trioxide supported on silica. These reactions were performed by flowing a solution of the alcohol in scCO2 through a column containing the supported reagent and recovering the product by depressurization. This method avoids the use of organic solvents and the contamination of the products with chromium species.

ChemInform Abstract: Efficient Synthesis of Racemic and Chiral Alkenyl Sulfoxides by Palladium-Catalyzed Suzuki Coupling.

Alkenyl sulfoxide derivatives are obtained in high yields through a palladium-catalyzed Suzuki/Miyaura cross-coupling reaction of racemic and chiral 1-halo sulfoxides with aryl and alkenyl boronic acids. Chiral substrates react with no loss of optical purity and high optical yields. The reaction takes place with different palladium catalysts, such as Pd(PPh 3 ) 4 or Pd(OAc) 2 /DABCO. Although nitrogen ligands like DABCO lead to an active palladium catalyst, they are less effective than the phosphine ones.

Enzyme-mediated enantioselective acylation of secondary amines in organic solvents

Abstract Porcine pancreatic lipase (PPL) and lipase Amano P catalyze the enantioselective acylation of cyclic 1,2- and 1,3-amino alcohol derivatives in organic solvents. The enatiomeric excesses (ee′s) were shown to depend on the enzyme, reaction time, temperature and type of substrate.

ChemInform Abstract: Acid-Mediated Reaction of Bis(pyridine)iodonium(I) Tetrafluoroborate with Aromatic Compounds. A Selective and General Iodination Method.

Reaction of aromatic compounds with bis(pyridine)iodonium(I) tetrafluoroborate (IPy2BF4) in the presence of HBF4 or CF3SO3H in CH2Cl2 at room temperature furnishes monoiodo derivatives with excellent regioselectivity and yields. Use of either acid gives comparable results with activated aromatics, whereas CF3SO3H is much more effective in the iodination of deactivated aromatics. © 1993 American Chemical Society.

Preparation of N,O-Aminals as Synthetic Equivalents of H2C=NAr and (H2C=NHAr)+ Ions: Neutral and Acid-promoted Transformations

A general method for the synthesis of N,O-aminals derived from primary aromatic amines is described. The reactivity of these compounds under neutral and acidic conditions has been studied and the title compounds can be envisaged as general purpose H2C=NAr or (H2C=NHAr)+ equivalents. N,O-Aminals have been converted into perhydrotriazines by moderate heating and into bis(4-aminoaryl) methane derivatives or N-benzylarylamines, respectively when heated in acidic media with pH control. Reduction of N, O-acetals with sodium cyanoborohydride has revealed that the C-O bond is broken exclusively in acidic media.

Epoxidation of Olefins with a Silica-Supported Peracid

Anhydrous [2-percarboxyethyl] functionalized silica (2a) is an advantageous oxidant for performing the epoxidation of olefins 1. Epoxides 3 do not undergo the ring-opening reactions catalyzed by the acidic silica surface, except for particularly activated cases such as styrene oxide. The hydrophilic and acidic character of the silica surface does not interfere with the directing effects exerted by allylic H-bond acceptor substituents. The alkenes 1 carrying hydroxyl groups react with silica-supported peracid 2a faster than unsubstituted alkenes, thus reversing the trend known for reactions with soluble peracids. These results are attributed to the H-bond interactions of substrate 1 with the…

Anaerobic Palladium-Catalyzed Chemoselective Oxidation of Allylic and Benzylic Alcohols with α-Bromo Sulfoxide as a Co-Oxidant.

A chemoselective palladium-catalyzed anaerobic oxidation of allylic and benzylic alcohols using an α-bromo sulfoxide as a co-oxidant is described for the first time. The catalyst system is simple and has a long life because of the allowance of phosphane ligands under the non-aerobic conditions. The advantages of the described method include no overoxidation of primary alcohols to carboxylic acids because of the mild conditions applied, the tolerance of oxygen-sensitive functionalities such as a carbon-carbon double bond, an organothio group, or a diorganoamino group and the effective preparation of α,β-unsaturated aldehydes and ketones, resulting from the oxidation of primary and secondary …

Favoring alkane primary carbon-hydrogen bond functionalization in supercritical carbon dioxide as reaction medium

The selectivity of a catalytic alkane functionalization process can be modified just changing the reaction medium from neat alkane to supercritical carbon dioxide (scCO2). A silica supported copper complex bearing an Nheterocyclic carbene ligand promotes the functionalization of carbon-hydrogen bonds of alkanes by transferring the CHCO2Et group from N2=CHCO2Et (ethyl diazoacetate, EDA). In neat hexane only 3% of the primary C-H bonds (ethyl heptanoate being the product) are functionalized in that manner, whereas the same reaction carried out in scCO2 provides a 30% yield in this linear ester. Such effect seems to be induced by an electronic density flux from the NHC ligand to the surroundin…

Hyperconjugative Control by Remote Substituents of Diastereoselectivity in the Oxygenation of Hydrocarbons.

The oxidation of 2-substituted adamantanes (2) with TFDO (1) is reported. The data show a stereodifferentiation of the chemical environments induced by remote electron-withdrawing substituents which produces remarkable Z/E diastereoselectivity in the oxidation of the tertiary C(5)-H and C(7)-H bonds. The results show a bell-shaped correlation between the Z/E stereoselectivity and the substituent constant sigma(I), which is interpreted in terms of hyperconjugative stabilization of the diastereomeric transition states.

ChemInform Abstract: FeCl3·6H2O-Catalyzed Mukaiyama-Aldol Type Reactions of Enolizable Aldehydes and Acetals.

A general procedure for the title condensation of dimethylacetals derived from enolizable aldehydes with silyl enol ethers is developed using FeCl3 as the catalyst.

The introduction of fluorine atoms or trifluoromethyl groups in short cationic peptides enhances their antimicrobial activity

The effect of introducing fluorine atoms or trifluoromethyl groups in either the peptidic chain or the C-terminal end of cationic pentapeptides is reported. Three series of amide and ester peptides were synthesised and their antimicrobial properties evaluated. An enhanced activity was found in those derivatives whose structure contained fluorine, suggesting an increase in their hydrophobicity.

Functionalization of CnH2n+2Alkanes: Supercritical Carbon Dioxide Enhances the Reactivity towards Primary Carbon-Hydrogen Bonds

The functionalization of the primary sites of alkanes is one of the more challenging areas in catalysis. In this context, a novel effect has been discovered that is responsible for an enhancement in the reactivity of the primary C-H bonds of alkanes in a catalytic system. The copper complex Cu(NCMe) (=hydrotris{[3,5-bis(trifluoromethyl)-4-bromo]-pyrazol-1-yl}borate) catalyzes the functionalization of CnH2n+2 with ethyl diazoacetate upon inserting the CHCO2Et unit into C-H bonds. In addition, the selectivity of the reaction toward the primary sites significantly increased relative to that obtained in neat alkane upon using supercritical carbon dioxide as the reaction medium. This was attribu…

ChemInform Abstract: Epoxidation of Olefins with a Silica-Supported Peracid in Supercritical Carbon Dioxide under Flow Conditions.

Anhydrous 2-percarboxyethyl-functionalized silica (2b), a recyclable supported peracid, is a suitable reagent to perform the epoxidation of alkenes 1 in supercritical carbon dioxide at 250 bar and 40 °C under flow conditions. This procedure simplifies the isolation of the reaction products and uses only carbon dioxide as a solvent under mild conditions. The solid reagent 2b can be easily recycled by a reaction with 30% hydrogen peroxide in an acid medium.

ChemInform Abstract: Epoxidation of Olefins with a Silica-Supported Peracid.

Anhydrous [2-percarboxyethyl] functionalized silica (2a) is an advantageous oxidant for performing the epoxidation of olefins 1. Epoxides 3 do not undergo the ring-opening reactions catalyzed by the acidic silica surface, except for particularly activated cases such as styrene oxide. The hydrophilic and acidic character of the silica surface does not interfere with the directing effects exerted by allylic H-bond acceptor substituents. The alkenes 1 carrying hydroxyl groups react with silica-supported peracid 2a faster than unsubstituted alkenes, thus reversing the trend known for reactions with soluble peracids. These results are attributed to the H-bond interactions of substrate 1 with the…

ChemInform Abstract: Gold(I)-Catalyzed Intermolecular Oxyarylation of Alkynes: Unexpected Regiochemistry in the Alkylation of Arenes.

The reaction between acetylenes and sulfoxides, studied as a test case for gold-catalyzed intermolecular addition, provides the oxyarylation compounds 3 in good yields. Unpredictably, in all cases a single regioisomer arising from the electrophilic aromatic alkylation at the position adjacent to the sulfur atom is obtained instead of the expected Friedel−Crafts regioisomer. A new concerted mechanism based on DFT calculations is proposed to account for the products in this intermolecular gold(I)-catalyzed reaction.

ChemInform Abstract: Water-Soluble Palladium Nanoparticles: Click Synthesis and Applications as a Recyclable Catalyst in Suzuki Cross-Couplings in Aqueous Media.

Polyethylene glycol-tagged macrocycle (I) is prepared by a three-fold copper-catalyzed [3 + 2] cycloaddition reaction.

Enantioselective Protonation of the Lithium Transient Enolate of2-Methyltetralone with 2-Sulfinyl Alcohols

A new catalytic cycle for the enantioselective protonation of cyclic ketone enolates with sulfinyl alcohols has been developed. An enol trifluoroacetate that can be easily obtained from the corresponding ketone is used for the first time as an enolate precursor of a cyclic ketone enolate. In this method, the achiral alcohol plays two roles: it is involved, as is usual in catalytic asymmetric protonation reactions, in the turnover of the chiral proton source and also in the generation of a transient enolate through the reaction of its corresponding alkoxide with the enol trifluoroacetate precursor. Stereoselectivity is highly dependent on the structure of the achiral alcohol. High levels of …

The role of Zn2+ in enhancing the rate and stereoselectivity of the aldol reactions catalyzed by the simple prolinamide model

Abstract The aldol reaction between acetone and 4-nitrobenzaldehyde catalyzed by single l -prolinamide and its zinc complexes has been studied. An increase in the rate and the stereoselectivity of the reaction has been shown by using zinc derivatives. A mechanistic proposal, based on NMR and ESI studies, has been put forward to explain the experimental data: zinc–prolinamide complexes catalyze the reaction following the general mechanism of stereoselective enamine nucleophilic addition to the acceptor aldehyde. Zn2+ prevents the nonspecific base-catalyzed reaction by diminishing the basicity of the amine nitrogen of prolinamide.

Palladium-catalyzed Suzuki-Miyaura reaction involving a secondary sp3 carbon: studies of stereochemistry and scope of the reaction.

Palladium-catalyzed C--C bond formation involving secondary sp3-hybridized carbon is described. These reactions occur with secondary 1-bromoethyl arylsulfoxides and different arylboronic acids, to produce the corresponding arylated sulfoxides in moderate to high yields and with complete stereospecificity. Despite the presence of beta hydrogens in the substrate, the competitive beta-hydride elimination is not a significant side reaction when coordinating solvents are used. The reported cross-coupling involves secondary C(sp3)--C(sp2) bond formation: this is the first time that a mechanistic study has been carried out with such substrates. The reaction proceeds with inversion of configuration…

A simple and general synthesis of symmetrical and unsymmetrical bis(arylamino)methanes. Reactions of N,O‐acetals with nitrogen bases

Bis(arylamino)methanes 4 free of amine contamination have been efficiently synthesized from N,O-acetals 1 following three different methodologies. The first two are useful for symmetrical aminals and involve the decomposition of an N,O-acetal by a base (phenyllithium or a lithium arylamide) and trapping of the resulting methyleneamine 2 by the equimolar amount of the corresponding arylamine. The third method allows the preparation of either symmetrical or unsymmetrical aminals and consists of decomposing the starting N,O-acetal 1 by heating in vacuo in the presence of the desired arylamine. Ein einfacher und allgemeiner Zugang zu symmetrischen und unsymmetrischen Bis(arylamino)methanen. Rea…

NHC-Stabilized Gold(I) Complexes: Suitable Catalysts for 6-exo-dig Heterocyclization of 1-(o-Ethynylaryl)ureas

3-Substituted 1-(o-ethynylaryl)ureas 1 selectively undergo either 6-exo-dig or 5-endo-dig cyclization (to give 4-methylene-3,4-quinazolin-2-ones 2 or indoles 3, respectively) depending on the choice of the metal, ligand, and reaction conditions. The best results (up to 96% yield) in the preparation of the hydroamination products 2 are achieved with the highly bulky NHC-stabilized cationic gold(I) complex [Au(IPr)](+). Conversely, ureas bearing an internal alkyne lead to the 5-endo-dig cyclization mode regardless of the gold(I) complex employed. Whereas the nature of the substituent at N-3 does not have any influence on the regiochemistry observed, it does, in some cases, affect the efficien…

Efficient synthesis of racemic and chiral alkenyl sulfoxides by palladium-catalyzed Suzuki coupling

Alkenyl sulfoxide derivatives are obtained in high yields through a palladium-catalyzed Suzuki/Miyaura cross-coupling reaction of racemic and chiral 1-halo sulfoxides with aryl and alkenyl boronic acids. Chiral substrates react with no loss of optical purity and high optical yields. The reaction takes place with different palladium catalysts, such as Pd(PPh 3 ) 4 or Pd(OAc) 2 /DABCO. Although nitrogen ligands like DABCO lead to an active palladium catalyst, they are less effective than the phosphine ones.

Iodomethane Oxidation by Dimethyldioxirane:  A New Route to Hypoiodous Acid and Iodohydrines

The oxidation of iodomethane with dimethyldioxirane allows the generation of stable neutral solutions of hypoiodous acid in the absence of any trapping agent for iodide anion. Hypoiodous acid is trapped in situ by addition to representative olefins to give iodohydrines in good yields. The stereochemical study of the products shows the anti-stereospecific nature of the iodohydroxylation reaction.

Oxyfunctionalization of Aliphatic Esters by Methyl(trifluoromethyl)dioxirane

The oxidation of lineal, cyclic, and bicyclic aliphatic p-chlorobenzoic and p-chorobenzenesulfonic acid esters 2 with methyl(trifluoromethyl)dioxirane (TFDO) (1) occurs at positions in the hydrocarbon chain distant from the directing group with a significant degree of selectivity to give the corresponding keto or hydroxy esters. Compounds 2 are relatively deactivated with respect to this oxidation due to the electron-withdrawing nature of the ester moiety. Methylene Cα−H and Cβ−H bonds remain unchanged in all cases, but tertiary Cβ−H bonds undergo oxidation with TFDO (1). Stereoelectronic factors are used to explain the faster reaction rate in competition experiments for the oxidation of en…

ChemInform Abstract: A Simple and General Synthesis of Symmetrical and Unsymmetrical Bis(arylamino)methanes. Reactions of N,O-Acetals with Nitrogen Bases.

Bis(arylamino)methanes 4 free of amine contamination have been efficiently synthesized from N,O-acetals 1 following three different methodologies. The first two are useful for symmetrical aminals and involve the decomposition of an N,O-acetal by a base (phenyllithium or a lithium arylamide) and trapping of the resulting methyleneamine 2 by the equimolar amount of the corresponding arylamine. The third method allows the preparation of either symmetrical or unsymmetrical aminals and consists of decomposing the starting N,O-acetal 1 by heating in vacuo in the presence of the desired arylamine. Ein einfacher und allgemeiner Zugang zu symmetrischen und unsymmetrischen Bis(arylamino)methanen. Rea…

ChemInform Abstract: Homogeneous Metal-Based Catalysis in Supercritical Carbon Dioxide as Reaction Medium

Above 31.1 °C and 73.8 bar, carbon dioxide reaches the supercritical state, being transformed into a fluid (scCO2) that has attracted interest in the last few decades as reaction medium for several transition-metal-catalyzed organic transformations. The main feature of this fluid rests on its capability to dissolve large amounts of other gases such as hydrogen, carbon monoxide, ethylene, or even methane and light alkanes. In this manner, very high concentrations of these reactants are available for catalysis. In this contribution a review of the main achievements of the use of transition-metal complexes as catalysts in scCO2 is presented.

ChemInform Abstract: Remarkable Effect of Lithium Bromide in the Enantioselective Protonation with α-Sulfinyl Alcohols.

Abstract The favourable effect of lithium bromide enhancing the facial enantioselectivity in the protonation of methyl tetralone enolate with α-sulfinyl alcohols is described. Theoretical calculations allow to propose a model to explain the stereochemical course of the protonation reaction.

Eine allgemeine und effiziente Methode zur Monohydroxylierung von Alkanen

Baeyer–Villiger oxidation of ketones with a silica-supported peracid in supercritical carbon dioxide under flow conditions

[2-Percarboxyethyl]-functionalized silica reacts with ketones in supercritical carbon dioxide at 250 bar and 40 °C under flow conditions to yield the corresponding esters and lactones. The solid reagent can be easily recycled through treatment with 70% hydrogen peroxide in the presence of an acid at 0 °C. This procedure not only simplifies the isolation of the reaction products, but has the advantage of using only water and carbon dioxide as solvents under mild conditions.

A study on the aminomercuration-nucleophilic demercuration of --1,5-cyclooctadiene; stereoselective synthesis of 2,6-disubstituted-9-aza bicyclo[3.3.1]nonanes

Abstract The aminomercuration of cis - cis -1,5-Cyclooctadiene with a series of mercury(II) salts followed by nucleophilic displacement of mercury by aromatic amines, water and nitrate ion has been studied. As a result, bicyclic triamines, aminoalcohols and nitrate esters have been obtained respectively in clean processes which occur under total stereoelectronic control by involvement of a tricyclic aziridium ion to afford a single stereoisomer in each case. The influence of the counter ion and the basicity of the amine on the tandem aminomercuration-demercuration is discussed.

Oxidation of Sulfides with a Silica-Supported Peracid in Supercritical Carbon Dioxide under Flow Conditions: Tuning Chemoselectivity with Pressure

Supercritical carbon dioxide is a convenient medium for performing the selective oxidation of sulfides 1 to either sulfoxides 2 or sulfones 3 with [2-percarboxyethyl]-functionalized silica (4) under flow conditions. The chemoselectivity of the reaction, which results from the different diffusion rates of sulfide and sulfoxide over the reagent bed, can be controlled by adjusting the pressure and the hydration of the silica surface as both the solvating power of the mobile phase and the surface activity of the stationary phase determine the migration rates of sulfide 1 and sulfoxide 2 over the supported peroxide. The results elucidate the impact of surface phenomena on the course of chemical …

Discovering Copper for Methane C–H Bond Functionalization

The copper complex Tp(CF3)2,BrCu(NCMe) (1, Tp(CF3)2,Br = hydrotris((3,5-bis(trifluoromethyl)-4-bromo)-pyrazol-1-yl)borate) catalyzes the insertion of the CHCO2Et group (from ethyl diazoacetate N2CHCO2Et, EDA) into the C–H bonds of methane, in a homogeneous process that uses supercritical carbon dioxide (scCO2) as the reaction medium. Other light alkanes such as ethane, propane, and butane have been also functionalized with this copper-based catalyst, in the first example of the derivatization of the series of C1–C4 alkanes with this metal and a soluble catalyst.

Dietary administration of high doses of pterostilbene and quercetin to mice is not toxic.

The aim of this study is to evaluate possible harmful effects of high doses of t-pterostilbene (t-PTER) and quercetin (QUER) in Swiss mice. Mice were fed during 28 days at doses of 0, 30, 300, and 3000 mg/kg body weight/day of t-PTER, QUER, or a mixture of both, t-PTER + QUER, which are equivalent to 5, 50, and 500 times, respectively, the estimated mean human intake of these polyphenols (25 mg/day). Daily oral administration of QUER, t-PTER, or a mixture of both of them did not cause mortality during the experimental period. There were no differences in food and water consumption on sex. No significant body weight gain in the male or female groups was observed. Red blood cell number and th…

ChemInform Abstract: Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of α-Halomethyl Oxime Ethers and Site-Selective Cross-Coupling of Dihalo Derivatives.

The Pd-catalyzed cross-coupling reaction of chloromethyl oxime ethers with a wide range of aryl-, heteroaryl-, and vinylboronic acids proceeds with good yields.

Mechanism of the Oxidation of Sulfides by Dioxiranes. 1. Intermediacy of a 10-S-4 Hypervalent Sulfur Adduct

Earlier studies established that dimethyldioxirane (1a) reacts with sulfides 2 in two consecutive concerted electrophilic oxygen-transfer steps to give first sulfoxides 3 and then sulfones 4. The same sequential electrophilic oxidation model was assumed for the reaction of sulfides 2 with the strongly electrophilic methyl(trifluoromethyl)dioxirane (1b). In this paper we report on a systematic and general study on the mechanism of the reaction of simple sulfides 2 with DMDO (1a) and TFDO (1b) which provides clear evidence for the involvement of hypervalent sulfur species in the oxidation process. In the oxidation of sulfides 2a-c, diphenyl sulfide (2d), para-substituted aryl methyl sulfides …

Palladium-Catalyzed Reaction of Boronic Acids with Chiral and Racemic ?-Bromo Sulfoxides.

Palladium-catalyzed cross-coupling reactions of racemic α-bromo sulfoxides with boronic acids are carried out in either aqueous or nonaqueous medium with formation of a new C sp3−C sp2 bond. The arylation of chiral α-bromo sulfoxides occurs without racemization. The cross-coupling reaction is general and gives high yields with arylboronic acids substituted with either donor or acceptor groups but gives poor results with heteroarylboronic acids. The best yields are obtained using degassed solvents and CsF instead of aqueous base. The use of aqueous base and the presence of oxygen favor the homocoupling side reaction.

I(py)2BF4, a New Reagent in Organic Synthesis: General Method for the 1,2-Iodofunctionalization of Olefins

The oxidation of alkanes with dimethyldioxirane; a new mechanistic insight

Abstract Primary kinetic isotope effects were measured for the oxidation of cyclohexane and methylcyclohexane with DMDO in solution and in the gas phase. These experiments suggest an electrophilic oxygen insertion mechanism for the oxidation of alkanes by DMDO.

Iodine-Induced Stereoselective Carbocyclizations: A New Method for the Synthesis of Cyclohexane and Cyclohexene Derivatives

Selective "one-pot" synthesis of functionalized cyclopentenones.

Double addition (1,2-1,4) of vinyl magnesium bromide to squaric acid derivatives allows the preparation of polyoxygenated cyclopentenones (8) in a "one-pot" procedure. The reaction occurs through the intermediate formation of octatetraenes (6). Protonation of this latter intermediate at -78 °C with TFE occurs selectively at the vinyl CH(2) closer to the metallic centers. DFT studies of the cyclization step justify the observed diastereoselectivity.

An improved method for the asymmetric protonation of enolates with chiral α-sulfinyl alcohols/trifluoroethanol

Abstract Enantioselective protonation of 2-methyl tetralone enolate using a stoichiometric amount of 2-sulfinyl alcohol ( S , R s )- 1 as a chiral proton donor yields the corresponding chiral ketone with a high level of enantioselectivity, provided that the chiral proton donor (CPD) is regenerated with an achiral proton source (APS). In contrast, stereoselectivity was only moderate if catalytic CPD (0.2 equiv.) and an APS are used.

Acid-mediated reaction of bis(pyridine)iodonium(I) tetrafluoroborate with aromatic compounds. A selective and general iodination method

Reaction of aromatic compounds with bis(pyridine)iodonium(I) tetrafluoroborate (IPy2BF4) in the presence of HBF4 or CF3SO3H in CH2Cl2 at room temperature furnishes monoiodo derivatives with excellent regioselectivity and yields. Use of either acid gives comparable results with activated aromatics, whereas CF3SO3H is much more effective in the iodination of deactivated aromatics. © 1993 American Chemical Society.

Effect of addition of Lewis/Brönsted acids in the asymmetric aldol condensation catalyzed by trifluoroacetate salts of proline-based dipeptides

Abstract Proline-based dipeptides catalyze aldol condensations with good yield and stereoselectivity after addition of zinc or sodium acetate to the trifluoroacetate peptide. The chirality of the N-terminal proline in the catalyst determines the absolute configuration of the aldol product, but stereoselectivity depends on the configuration of both amino acids, and is higher for the enantiomeric pair R–S, S–R. Regarding the nature of the second component, optimal results in both yield and stereoselectivity are obtained when neutral unbranched primary amino acids are used.

A General and Efficient Method for the Monohydroxylation of Alkanes

ChemInform Abstract: NHC-Stabilized Gold(I) Complexes: Suitable Catalysts for 6-exo-dig Heterocyclization of 1-(o-Ethynylaryl)ureas.

Under the optimized gold catalysis, the less favored and more challenging 6-exo-dig cyclized products are formed in yields up to 96% from ureas bearing a terminal alkyne at the ortho-position.

ChemInform Abstract: Iodine-Induced Stereoselective Carbocyclizations - A New Method for the Synthesis of Cyclohexane and Cyclohexene Derivatives.

Silver-Catalyzed C-C Bond Formation between Methane and Ethyl Diazoacetate in Supercritical CO2

Even in the context of hydrocarbons’ general resistance to selective functionalization, methane’s volatility and strong bonds pose a particular challenge. We report here that silver complexes bearing perfluorinated indazolylborate ligands catalyze the reaction of methane (CH4) with ethyl diazoacetate (N2CHCO2Et) to yield ethyl propionate (CH3CH2CO2Et). The use of supercritical carbon dioxide (scCO2) as the solvent is key to the reaction’s success. Although the catalyst is only sparingly soluble in CH4/CO2 mixtures, optimized conditions presently result in a 19% yield of ethyl propionate (based on starting quantity of the diazoester) at 40°C over 14 hours.

Gold(I)-Catalyzed Reactions of 1-(ortho-Alkynylaryl)ureas: Highly Selective Heterocyclization and Synthesis of MixedN,O-Acetals

Treatment of alkynylureas (I) with trifluoroethanol in the presence of a Au/Ag catalytic system provides N-6-exo-dig heterocyclization products (III) and in some cases open chain acetals as side products.

ChemInform Abstract: Catalytic Aminomercuration of Olefins in a Tandem Aminomercuration-Deoxymercuration; One-Step Synthesis of Secondary N-Arylallylamines from Allylalcohols.

Abstract Allyl alcohols react with primary aromatic amines and stoichiometric amounts of mercury(II) tetrafluoroborate to give mixtures of mono- and diallyl anilines. However, the use of the tandem aminomercuration-deoxymercuration promoted by catalytic mercury(II) tetrafluoroborate allows to perform regiospecifically the monoallylation reaction with very high yields. A mechanism is proposed to account for the observed results.

Inhibition of imidazolidinone intermediate formation in the aldol reactions catalyzed by zinc–prolinamide complexes

Abstract The use of zinc salts as cocatalysts in aldol condensations catalyzed by single prolinamide (and in the extension by other more complex prolinamides) can prevent the formation of the parasitic intermediate imidazolidinone, with faster and also more stereoselective reactions than those catalyzed by the free amine. This new finding, together with this ion’s already known properties, make zinc salts highly suitable additives for aldol reactions catalyzed for prolinamide derivatives.

Measuring the Relative Reactivity of the Carbon-Hydrogen Bonds of Alkanes as Nucleophiles

We report quantitative measurements of the relative reactivities of a series of C-H bonds of gaseous or liquid CnH2n+2 alkanes (n = 1-8, 29 different C-H bonds) towards insitu generated electrophiles (copper, silver, and rhodium carbenes), with methane as the reference. This strategy surpasses the drawback of previous model reactions of alkanes with strong electrophiles suffering from C-C cleavage processes, which precluded direct comparison of the relative reactivities of alkane C-H bonds.

Catalytic aminomercuration of olefins in a tandem aminomercuration-deoxymercuration; One-step synthesis of secondary n-arylallylamines from allylalcohols

Abstract Allyl alcohols react with primary aromatic amines and stoichiometric amounts of mercury(II) tetrafluoroborate to give mixtures of mono- and diallyl anilines. However, the use of the tandem aminomercuration-deoxymercuration promoted by catalytic mercury(II) tetrafluoroborate allows to perform regiospecifically the monoallylation reaction with very high yields. A mechanism is proposed to account for the observed results.

One electron transfer chain decomposition of trifluoroacetone diperoxide: The first 1,2,4,5-tetroxane with O-transfer capability

Abstract Reaction of 1,1,1-trifluoropropanone (trifluoroacetone) ( 1a ) with 30% hydrogen peroxide in the presence of conc. sulfuric acid afforded in good yield 3,6-bis(trifluoromethyl)-3,6-dimethyl-1,2,4,5-tetroxane or trifluoroacetone diperoxide ( 2a ). Peroxide 2a is quantitatively converted into trifluoroacetone ( 1a ) and dioxygen by a catalytic amount of tetrabutylammonium iodide through a reductive electron transfer chain reaction carried out by the superoxide ion. Trifluoroacetone diperoxide ( 2a ) is capable of O-atom transfer to alkenes and sulfides.

Oxygenation of Alkane C−H Bonds with Methyl(trifluoromethyl)dioxirane:  Effect of the Substituents and the Solvent on the Reaction Rate

[Chemical reaction: See text] The mechanism of the oxygenation of alkane C-H bonds with methyl(trifluoromethyl)dioxirane (1a) is studied through the effect of the substituent and solvent on the rate of oxygenation of 2-substituted adamantanes (2). The results suggest a remarkable electron deficiency at the reacting carbon atom in the transition state leading to the regular oxygenation products. The linearity of the Hammett plot reveals that the reaction mechanism does not change within a range of 0.15-0.67 units of sigma(I). A change in the solvent does not affect the distribution of the products, indicating a through-bond transmission of the substituent effect as the origin of the deactiva…

Oppenauer Oxidation of Secondary Alcohols with 1,1,1-Trifluoroacetone as Hydride Acceptor

1,1,1-Trifluoroacetone (2a) reacts as a hydride-acceptor in the Oppenauer oxidation of secondary alcohols (1) in the presence of diethylethoxyaluminum. The oxidant allows for selective oxidation of secondary alcohols in the presence of primary alcohols.

Osmium(III) Complexes with POP Pincer Ligands: Preparation from Commercially Available OsCl3·3H2O and Their X-ray Structures

Complexes OsCl3{dbf(PiPr2)2} [1; dbf(PiPr2)2 = 4,6-bis(diisopropylphosphino)dibenzofuran], OsCl3{xant(PiPr2)2} [2; xant(PiPr2)2 = 9,9-dimethyl-4,5-bis(diisopropylphosphino)xanthene], and OsCl3{xant(PPh2)2} [3; xant(PPh2)2 = 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene] have been obtained in high yield by the reaction of the corresponding diphosphine with OsCl3·3H2O. The ruthenium(III) counterparts RuCl3{dbf(PiPr2)2} (4), RuCl3{xant(PiPr2)2} (5), and RuCl3{xant(PPh2)2} (6) are similarly obtained from RuCl3·3H2O in moderate yields. The X-ray structures of dbf(PiPr2)2 and complexes 1−3 are also reported.

Palladium-Catalyzed C-C Ring Closure in α-Chloromethylimines: Synthesis of 1H -Indoles

Isomerization versus decarboxylation of protonated oxetanone: Comparison between experimental results and theoretical calculations

Palladium-catalyzed reaction of boronic acids with chiral and racemic alpha-bromo sulfoxides.

Palladium-catalyzed cross-coupling reactions of racemic alpha-bromo sulfoxides with boronic acids are carried out in either aqueous or nonaqueous medium with formation of a new C sp(3)-C sp(2) bond. The arylation of chiral alpha-bromo sulfoxides occurs without racemization. The cross-coupling reaction is general and gives high yields with arylboronic acids substituted with either donor or acceptor groups but gives poor results with heteroarylboronic acids. The best yields are obtained using degassed solvents and CsF instead of aqueous base. The use of aqueous base and the presence of oxygen favor the homocoupling side reaction.

Conformational mobility of thianthrene-5-oxide.

[reaction: see text] Data on the apparent dipole moment of thianthrene-5-oxide (1) and (1)H NMR spectra in different solvents support the conformational mobility of 1, which flaps between two limit boat conformations with the sulfinyl group in pseudoequatorial and pseudoaxial positions, respectively. The conformational equilibrium of 1 occurs too fast for the (1)H NMR (500 MHz) time-scale even at -130 degrees C, and the equilibrium constant has not been determined. The apparent dipole moments of 1 in n-hexane and 1,4-dioxane and the (1)H NMR spectra of 1 and the model compounds cis- and trans-thianthrene-5,10-dioxides (2) and thianthrene (5) in different solvents and at various temperatures…

Influence of Remote Substituents on the Equatorial/Axial Selectivity in the Monooxygenation of Methylene C−H Bonds of Substituted Cyclohexanes

The reactivity of individual C--H bonds in the methyl(trifluoromethyl)dioxirane TFDO oxygenation of stereogenic methylene groups in conformationally homogeneous monosubstituted cyclohexanes (2) has been determined. The unexpectedly high occurrence of O-atom insertion into C--H(ax) bonds suggests an in plane trajectory attack in the oxygenation while the diastereoselectivity of the reaction is qualitatively interpreted on the basis of the distinct hyperconjugative stabilization by the substituent of diastereomeric transition states due to long-range through bond interactions.

Baeyer−Villiger Oxidation with Potassium Peroxomonosulfate Supported on Acidic Silica Gel

[reaction: see text] Potassium peroxomonosulfate deposited onto silica SiO2 x KHSO5 efficiently reacts with ketones in dichloromethane at room temperature to give the corresponding esters or lactones in quantitative yields. This method avoids hydrolysis of the reaction products. The Baeyer-Villiger reaction is catalyzed by potassium hydrogensulfate present in the supported reagent.

Iod-induzierte stereoselektive Carbocyclisierungen – Beispiele für eine breit anwendbare, neue Methode zur Synthese von Cyclohexan- und -hexen-Derivaten

On the Importance of Carbohydrate-Aromatic Interactions for the Molecular Recognition of Oligosaccharides by Proteins: NMR Studies of the Structure and Binding Affinity of AcAMP2-like Peptides with Non-Natural Naphthyl and Fluoroaromatic Residues

The specific interaction of a variety of modified hevein domains to chitooligosaccharides has been studied by NMR spectroscopy in order to assess the importance of aromatic-carbohydrate interactions for the molecular recognition of neutral sugars. These mutant AcAMP2-like peptides, which have 4-fluoro-phenylalanine, tryptophan, or 2-naphthylalanine at the key interacting positions, have been prepared by solid-phase synthesis. Their three-dimensional structures, when bound to the chitin-derived trisaccharide, have been deduced by NMR spectroscopy. By using DYANA and restrained molecular dynamics simulations with the AMBER 5.0 force field, the three-dimensional structures of the protein-sugar…

Antimicrobial Peptides and Their Superior Fluorinated Analogues: Structure-Activity Relationships as Revealed by NMR Spectroscopy and MD Calculations

9 pag., 6 fig, 3 tab.

Mechanism of the oxidation of sulfides by dioxiranes: conformational mobility and transannular interaction in the oxidation of thianthrene 5-oxide.

The detailed study of the oxidation of thianthrene 5-oxide (1) with methyl(trifluoromethyl)dioxirane (5b) in different solvents and in the presence of (18)O isotopic tracers is reported. Thianthrene 5-oxide (1) is a flexible molecule in solution, and this property allows for transannular interaction of the sulfoxide group with the expected zwitterionic 7 and hypervalent 10-S-4 sulfurane 9 intermediates formed in the oxidation and biases the course of the reaction toward the monooxygenation pathway.

FeCl3·6H2O-catalyzed Mukaiyama-aldol type reactions of enolizable aldehydes and acetals.

Mukaiyama-aldol type reactions of acetals derived from enolizable aldehydes with FeCl3·6H2O, an eco-friendly, low-cost, and stable catalyst, lead to β-methoxycarbonyl compounds with nearly quantitative yields. The methodology is extended to the parent aldehydes as starting materials, leading to the corresponding aldols with lower yields, but efficiently. Different alkyl and aryl substituted acetals and aldehydes have been tested in the reaction with linear and cyclic silyl enol ethers. Reactions are carried out in an open air atmosphere, and additives are not required. Acetals can be considered activating groups of the carbonyl moiety rather than a protecting group in this type of FeCl3·6H2…

Counterion's Effect on the Catalytic Activity of Zn-Prolinamide Complexes in Aldol Condensations

The catalytic activity of complexes involving organic ligands and Lewis acids can be modulated by changing any of their components. In this work we have studied the influence on the stereoselectivity and catalytic activity exerted by the counterion of zinc salts employed as cocatalysts of L-prolinamide in aldol condensations. The structures of the complexes have been determined both in solution and in the solid state.

Inverse solvent effects in the heterogeneous and homogeneous epoxidation of cis-2-heptene with [2-percarboxyethyl]-functionalized silica and meta-chloroperbenzoic acid.

The rate constants for the epoxidation of cis-2-heptene with [2-percarboxyethyl]-functionalized silica (1a) and meta-chloroperbenzoic acid (mCPBA) (1b) in different solvents have been determined at temperatures in the −10 to 40 °C range. The heterogeneous epoxidation exhibits a dependence of the reaction rate on solvent polarity opposite to its homogeneous counterpart and anomalous activation parameters in n-hexane, which are interpreted in terms of the surface-promoted solvent structure at the solid–liquid interface. The results show that highly polar solvents can strongly inhibit heterogeneous reactions performed with silica-supported reagents or catalysts.

The Role of Organic Fluorine in the Supramolecular Assembly of Halogenated β-Hydroxysulphoxides Diastereomers

A series of optically pure γ-halogenated β-hydroxysulphoxides containing two stereogenic centers have been prepared, and the X-ray crystal structures have been determined. The conformational behavior in the solid state and the crystal packing of the different β-hydroxysulphoxide diastereoisomers have been determined. The intermolecular and intramolecular interactions present have been studied in both halogenated and nonhalogenated β-hydroxysulphoxides to establish the influence of the halogen atom in the supramolecular structure. The main intermolecular hydrogen bond OH···OS is always present and produces molecular chains. Self-assembly of these chains includes weak CH···F, C−F···F−C, and C…

Water compatible gold(III)-catalysed synthesis of unsymmetrical ethers from alcohols.

An efficient and broad-scoped method for the preparation of unsymmetrical ethers from alcohols catalysed by the simplest and least expensive gold catalyst, NaAuCl 4 , is described for the first time. The procedure enables the etherification of benzylic and tertiary alcohols with moderate to good yields under mild conditions with low catalyst loading. Symmetrical ethers, the usual side products in the etherification of alcohols, were not detected in this case. The formation of the racemic ether from a chiral benzyl alcohol suggests the intermediacy of a carbocation, which has not previously been postulated for gold-catalysed reactions involving alcohols.

Homogeneous Metal-Based Catalysis in Supercritical Carbon Dioxide as Reaction Medium

Above 31.1 degrees C and 73.8 bar, carbon dioxide reaches the supercritical state, being transformed into a fluid (scCO(2)) that has attracted interest in the last few decades as reaction medium for several transition-metal-catalyzed organic transformations. The main feature of this fluid rests on its capability to dissolve large amounts of other gases such as hydrogen, carbon monoxide, ethylene, or even methane and light alkanes. In this manner, very high concentrations of these reactants are available for catalysis. In this contribution a review of the main achievements of the use of transition-metal complexes as catalysts in scCO(2) is presented.

ChemInform Abstract: Aryl Radicals by Copper(II) Oxidation of Hydrazines: A New Method for the Oxidative and Reductive Arylation of Alkenes.

Abstract A new source of aryl radicals interesting from the preparative point of view has been found in the reaction of arylhydrazines and copper(II) sulfate. The process allows selectively both the reductive and oxidative arylation of alkenes.

SN1 Reactions in Supercritical Carbon Dioxide in the Presence of Alcohols: the Role of Preferential Solvation

Ethanol (3b) inhibits SN1 reactions of alkyl halides 1 in supercritical carbon dioxide (scCO2) and gives no ethers as products. The unexpected behaviour of alcohols 3 in the reaction of alkyl halides 1 with 1,3-dimethoxybenzene (2) in scCO2 under different conditions is rationalised in terms of Bronsted and Lewis acid–base equilibria of reagents, intermediates, additives and products in a singular solvent characterised by: (i) the strong quadrupole and Lewis acid character of carbon dioxide, which hinders SN2 paths by strongly solvating basic solutes; (ii) the weak Lewis base character of carbon dioxide, which prevents it from behaving as a proton sink; (iii) the compressible nature of scCO…

I(py)2BF4, ein neues Reagens: allgemeine Methode für die 1,2-Iodfunktionalisierung von Olefinen

A new electrophilic addition to acetylenes. Synthesis of 1,2-iodofunctionalized olefins

Abstract Acetylenes react with bis(pyridine)iodo(I) tetrafluoroborate ( 1 ) in the presence of a wide variety of nucleophiles (F, Cl, Br, I, SCN, pyridine, OAc, anisole, H) to give 1,2-iodofunctionalized olefins ( 4 ).

ChemInform Abstract: Palladium-Catalyzed Alkoxy- and Aminocarbonylation of α-Halomethyl Oxime Ethers: Synthesis of 1,3-Alkoxyimino Esters and 1,3-Alkoxyimino Amides.

The three component reactions of α-bromomethyl oxime ethers, carbon monoxide, and alcohols or aromatic amines give imino esters and amides, respectively.

ChemInform Abstract: Gold(I)-Catalyzed Intermolecular Cycloaddition of Allenamides with α,β-Unsaturated Hydrazones: Efficient Access to Highly Substituted Cyclobutanes.

α,β-Unsaturated N,N-dialkyl hydrazones undergo a mild [2 + 2] cycloaddition to allenamides when treated with a suitable gold catalyst. The method, which represents the first application of N,N-dialkyl hydrazones in gold catalysis, is compatible with a wide variety of substituents at the alkenyl moiety of the hydrazone component, proceeds with excellent levels of regio- and diastereoselectivity, and provides densely substituted cyclobutanes with good to excellent yields.

ChemInform Abstract: Baeyer-Villiger Oxidation of Ketones with a Silica-Supported Peracid in Supercritical Carbon Dioxide under Flow Conditions.

[2-Percarboxyethyl]-functionalized silica reacts with ketones in supercritical carbon dioxide at 250 bar and 40 °C under flow conditions to yield the corresponding esters and lactones. The solid reagent can be easily recycled through treatment with 70% hydrogen peroxide in the presence of an acid at 0 °C. This procedure not only simplifies the isolation of the reaction products, but has the advantage of using only water and carbon dioxide as solvents under mild conditions.

Association between Pterostilbene and Quercetin Inhibits Metastatic Activity of B16 Melanoma

AbstractInhibition of cancer growth by resveratrol (trans-3,5,4'trihydroxystilbene; RESV), a phytoalexin present in many plant species, is limited by its low bioavailability. Pterostilbene (3,5-dimethoxy-4'-hydroxystilbene; PTER) and quercetin (3,3',4',5,6-pentahydroxyflavone; QUER), two structurally related and naturally occurring small polyphenols, show longer half-life in vivo. In vitro growth of highly malignant B16 melanoma F10 cells (B16M-F10) is inhibited (56%) by short-time exposure (60 min/day) to PTER (40 μM) and QUER (20 μM) (approximate mean values of plasma concentrations measured within the first hour after intravenous administration of 20 mg/kg of each polyphenol). Intravenou…

On the ionizing properties of supercritical carbon dioxide: uncatalyzed electrophilic bromination of aromatics

Supercritical carbon dioxide (scCO2), a solvent with a zero dipole moment, low dielectric constant, and no hydrogen bonding behavior, is a suitable medium to perform the uncatalyzed electrophilic bromination of weakly activated aromatics with no interference of radical pathways. The ability of scCO2 to promote these reactions matches those of strongly ionizing solvents such as aqueous acetic and trifluoroacetic acids. Conversely, carbon tetrachloride, with similar polarity parameters to scCO2, leads exclusively to side chain functionalization. The strong quadrupole moment, and the acidic, but non basic, Lewis character of carbon dioxide, are proposed as key factors for the singular performa…

From Overstoichiometric to Substoichiometric Enantioselective Protonation with 2-Sulfinyl Alcohols: A View in Perspective

A general study of the enantioselective protonation of prochiral enolates with 2-sulfinyl alcohols is reported. The modification of reaction conditions to reduce drastically the amount of chiral proton source needed to obtain a good enantiomeric excess is reported. The effects of the different factors controlling the stereoselectivity are clearly established. Different protocols for enolate generation are compared.

Palladium-Catalyzed Alkoxy- and Aminocarbonylation of α-Halomethyl Oxime Ethers: Synthesis of 1,3-Alkoxyimino Esters and 1,3-Alkoxyimino Amides

The three component reactions of α-bromomethyl oxime ethers, carbon monoxide, and alcohols or aromatic amines give imino esters and amides, respectively.

CCDC 965392: Experimental Crystal Structure Determination

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CCDC 1037192: Experimental Crystal Structure Determination

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CCDC 1029359: Experimental Crystal Structure Determination

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CCDC 1061399: Experimental Crystal Structure Determination

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CCDC 1029358: Experimental Crystal Structure Determination

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CCDC 965391: Experimental Crystal Structure Determination

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CCDC 1037194: Experimental Crystal Structure Determination

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CCDC 953983: Experimental Crystal Structure Determination

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CCDC 1037193: Experimental Crystal Structure Determination

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CCDC 953982: Experimental Crystal Structure Determination

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