Non-activated Substrates Research Articles

Nucleation and growth of plasma sputtered silver nanoparticles under acoustic wave activation

Early results on the plasma deposition of dielectric thin films on acoustic wave (AW) activated substrates revealed a densification pattern arisen from the focusing of plasma ions and their impact on specific areas of the piezoelectric substrate. Herein, we extend this methodology to tailor the plasma deposition of metals onto AW-activated LiNbO3 piezoelectric substrates. Our investigation reveals the tracking of the initial stages of nanoparticle (NP) formation and growth during the submonolayer deposition of silver. We elucidate the specific role of AW activation in reducing particle size, enhancing particle circularity, and retarding NP agglomeration and account for the physical phenomena making these processes differ from those occurring on non-activated substrates. We provide a comparative analysis of the results obtained under two representative plasma conditions: diode DC sputtering and magnetron sputtering. In the latter case, the AW activation gives rise to a 2D pattern of domains with different amounts of silver and a distinct size and circularity for the silver NPs. This difference was attributed to the specific characteristics of the plasma sheath formed onto the substrate in each case. The possibilities of tuning the plasmon resonance absorption of silver NPs by AW activation of the sputtering deposition process are discussed.

Reversible Oxidative Addition of Nonactivated C-H Bonds to Structurally Constrained Phosphenium Ions.

A series of structurally constrained phosphenium ions based on pyridinylmethylamidophenolate scaffolds are shown to undergo P(III)/P(V) oxidative addition with C-H bonds of alkynes, alkenes, and arenes. Nonactivated substrates such as benzene, toluene, and deactivated chlorobenzene are phosphorylated in quantitative yields. Computational and spectroscopic studies suggest a low-barrier isomerization from a bent to a T-shaped isomer that initiates a phosphorus-ligand-cooperative pathway and subsequent ring-chain tautomerism. Remarkably, C-H bond activations occur reversibly, allowing for reductive elimination back to P(III) at elevated temperatures or the exchange with other substrates.

A sonochemical approach for a silver particle layer SERS substrates preparation and subsequent application in qualitative analysis

We present an easy and efficient method for silver particle layer SERS substrate preparation that combines a modified Tollens’ approach with using ultrasound to obtain unique reaction conditions by generating high-energy hot-spots as the arising acoustic cavities implode. The silver layers were deposited on various substrates in a one-step reduction process of silver nitrate. Three different reductants (maltose, glucose, ascorbic acid) were used to obtain silver particle layers with different particle sizes, morphologies, and inter-particle distances. To further optimize the properties of the silver particles for SERS and to provide higher signal enhancement, all the prepared nanoparticle layers were activated in 4 M Cl− solution. The size of silver particles was in most samples under 100 nm and the particles formed clusters, but they were also present on the surface individually. In some of the activated substrates, bigger particles (0.5–1 μm) occur as well. The activated as well as non-activated substrates were tested as SERS substrates using 10−5 M adenine as a model analyte. Laser wavelengths of 455 nm, 532 nm, 633 nm, 780 nm, and 785 nm were used for the SERS measurements. High enhancement factors up to 3.5·105 and 2.8·105 were obtained for SERS measurements using lasers of 532 nm and 780 nm, respectively.

General Co-catalytic Hydrothiolation of gem-Difluoroalkenes.

Regioselective functionalization of gem-difluoroalkenes enables convergent late-stage access to fluorinated functional groups, though most functionalization reactions proceed through defluorinative functionalization processes that deliver mono-fluorovinyl products. In contrast, fewer reactions undergo net hydrofunctionalization to generate difluorinated products. Herein, we report a photocatalytic hydrothiolation of gem-difluoroalkenes that enables access to a broad spectrum of α,α-difluoroalkylthioethers. Notably, the reaction successfully couples nonactivated substrates, which expands the scope of accessible molecules relative to previously reported reactions involving organo- or photocatalytic strategies. Further, this reaction successfully couples biologically relevant molecules under aqueous conditions, highlighting potential applications in both late-stage and biorthogonal functionalizations.

Perdeuteration of Arenes via Hydrogen Isotope Exchange Catalyzed by the Superbasic Sodium Amide Donor Species NaTMP·PMDETA.

Hydrogen isotope exchange (HIE) has become one of the most studied methods to prepare deuterated molecules, with the primary focus recently on metal-catalyzed C-H activation with transition metals. Here we report the use of a simple sodium amide, NaTMP (TMP = 2,2,6,6-tetramethylpiperidide), combined with tridentate Lewis donor PMDETA (N,N,N',N″,N″-pentamethyldiethylenetriamine), which is able to catalytically promote the HIE of a series nonactivated arenes under mild reaction conditions using C6D6 as the deuterium source. Establishing the potential of NaTMP for the deuteration of aromatic molecules, several nonactivated substrates such as naphthalene, diphenylacetylene, and stilbene could be deuterated under mild reaction conditions without the need of transition metals. Combining NMR studies with the isolation of key organometallic intermediates, we demonstrate that the ability of NaTMP/PMEDTA to partially metalate C6D6, with concomitant generation of TMP(D), is key to enable the catalytic deuteration.

Multiple Activation Catalyst for Asymmetric [4+2] Cycloaddition of Aldehydes with Dienes

AbstractThe enantioselective oxa-Diels–Alder reaction of nonactivated substrates by utilizing FeCl3 and a 1,1′-bi-2-naphthol (BINOL) derived chiral phosphoric acid as a multiple activation catalyst is reported. Various oxygen-containing six-membered heterocycles were obtained in high yields and in an enantioselective manner. Density functional theory (DFT) calculations elucidate that both Lewis acidic and Brønsted acidic moieties in the catalyst system synergistically activate two lone pairs of an aldehyde to facilitate enantioselective addition reaction of dienes.

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids.

(R,R)-Dimethyl tartrate acetonide 7 in THF/HMPA undergoes deprotonation with LDA and reaction at −78 °C during 12–72 h with a range of alkyl halides, including non-activated substrates, to give single diastereomers (at the acetonide) of monoalkylated tartrates 17, 24, 33a–f, 38a,b, 41 of R,R-configuration, i.e., a stereoretentive process (13–78% yields). Separable trans-dialkylated tartrates 34a–f can be co-produced in small amounts (9–14%) under these conditions, and likely arise from the achiral dienolate 36 of tartrate 7. Enolate oxidation and acetonide removal from γ-silyloxyalkyl iodide-derived alkylated tartrates 17 and 24 give ketones 21 and 26 and then Bamford–Stevens-derived diazoesters 23 and 27, respectively. Only triethylsilyl-protected diazoester 27 proved viable to deliver a diazoketone 28. The latter underwent stereoselective carbonyl ylide formation–cycloaddition with methyl glyoxylate and acid-catalysed rearrangement of the resulting cycloadduct 29, to give the 3,4,5-tricarboxylate-2,8-dioxabicyclo[3.2.1]octane core 31 of squalestatins/zaragozic acids. Furthermore, monoalkylated tartrates 33a,d,f, and 38a on reaction with NaOMe in MeOH at reflux favour (≈75:25) the cis-diester epimers epi-33a,d,f and epi-38a (54–67% isolated yields), possessing the R,S-configuration found in several monoalkylated tartaric acid motif-containing natural products.

Highly Electrophilic Titania Hole as a Versatile and Efficient Photochemical Free Radical Source.

Photogenerated holes in nanometric semiconductors, such as TiO2, constitute remarkable powerful electrophilic centers, capable of capturing an electron from numerous donors such as ethers, or nonactivated substrates like toluene or acetonitrile, and constitute an exceptionally clean and efficient source of free radicals. In contrast with typical free radical precursors, semiconductors generate single radicals (rather than pairs), where the precursors can be readily removed by filtration or centrifugation after use, thus making it a convenient tool in organic chemistry. The process can be described as an example of dystonic proton coupled electron transfer.

Outer-Sphere Electrophilic Fluorination of Organometallic Complexes.

Organofluorine chemistry plays a key role in materials science, pharmaceuticals, agrochemicals, and medical imaging. However, the formation of new carbon-fluorine bonds with controlled regiochemistry and functional group tolerance is synthetically challenging. The use of metal complexes to promote fluorination reactions is of great current interest, but even state-of-the-art approaches are limited in their substrate scope, often require activated substrates, or do not allow access to desirable functionality, such as alkenyl C(sp(2))-F or chiral C(sp(3))-F centers. Here, we report the formation of new alkenyl and alkyl C-F bonds in the coordination sphere of ruthenium via an unprecedented outer-sphere electrophilic fluorination mechanism. The organometallic species involved are derived from nonactivated substrates (pyridine and terminal alkynes), and C-F bond formation occurs with full regio- and diastereoselectivity. The fluorinated ligands that are formed are retained at the metal, which allows subsequent metal-mediated reactivity.

A polyphenylene support for Pd catalysts with exceptional catalytic activity.

We describe a solid polyphenylene support that serves as an excellent platform for metal-catalyzed reactions that are normally carried out under homogeneous conditions. The catalyst is synthesized by palladium-catalyzed Suzuki coupling which directly results in formation of palladium nanoparticles confined to a porous polyphenylene network. The composite solid is in turn highly active for further Suzuki coupling reactions, including non-activated substrates that are challenging even for molecular catalysts.

The mechanism of patellamide macrocyclization revealed by the characterization of the PatG macrocyclase domain

Peptide macrocycles are found in many biologically active natural products. Their versatility, resistance to proteolysis and ability to traverse membranes has made them desirable molecules. Although technologies exist to synthesize such compounds, the full extent of diversity found among natural macrocycles has yet to be achieved synthetically. Cyanobactins are ribosomal peptide macrocycles encompassing an extraordinarily diverse range of ring sizes, amino acids and chemical modifications. We report the structure, biochemical characterization and initial engineering of the PatG macrocyclase domain of Prochloron sp. from the patellamide pathway that catalyzes the macrocyclization of linear peptides. The enzyme contains insertions in the subtilisin fold to allow it to recognize a three-residue signature, bind substrate in a preorganized and unusual conformation, shield an acyl-enzyme intermediate from water and catalyze peptide bond formation. The ability to macrocyclize a broad range of nonactivated substrates has wide biotechnology applications.

Retraction: Facile Palladium‐Catalyzed Arylation of Heterocycles and Nonactivated Arenes with Aryl Chlorides

Retraction: Facile Palladium‐Catalyzed Arylation of Heterocycles and Nonactivated Arenes with Aryl Chlorides

Mechanistic Analysis of the Blood Group Antigen-Cleaving endo-β-Galactosidase from Clostridium perfringens

The A and B antigens are of vital importance in blood transfusion and organ transplantation. The specificity of EABase, an endo-beta-galactosidase from C. perfringens, toward the cleavage of A and B trisaccharides from glycoconjugates is unique and holds significant potential for use in modifying blood group antigens on cell surfaces. The mechanism of this enzyme and others in its family (GH98) and the identities of its catalytic residues have not previously been experimentally determined. Direct 1H NMR analysis of the hydrolysis of a synthetic substrate, DNP-beta-A-trisaccharide, by EABase revealed that EABase is an inverting endo-beta-galactosidase. Both activated and nonactivated substrates were used to kinetically characterize EABase and its mutants (E354A, D429A, D453A, E467A, and E506A) at pH 6.0, 37 degrees C. Hydrolysis of DNP-beta-A-trisaccharide by EABase follows normal Michaelis-Menten kinetics with an apparent KM of 64 +/- 3 microM and a k(cat) of 105 +/- 5 min(-1). Mutation of two putative active site residues, D453 and E506, to alanine resulted in complete loss of activity, strongly suggesting that one or both of these residues functions as the base catalyst. The kinetic data also strongly suggest that E354 is the acid catalyst since the activity of the E354A mutant with nonactivated natural substrates is 1100-fold lower than that of the wild type enzyme, while its activity is only 10-fold lower when assayed with an activated aryl glycoside substrate (DNP-beta-A-trisaccharide). Further support is obtained through comparison of pH profiles for the wild type and E354A mutants: mutation of the acid catalyst eliminates the basic limb from the bell-shaped pH-dependence of k(cat)/KM seen for the wild type enzyme.

Piperazine-Derived Palladium Complexes Immobilised on a Merrifield Resin as a Catalyst for the Heck Reaction

A palladium catalyst supported on a Merrifield resin was prepared by a simple procedure and exhibited high activity and stability for the phosphine-free Heck reaction of activated and non-activated aryl or heteroaryl substrates with olefins to afford substituted cinnamic acids, stilbenes and their hetero-aromatic relatives.

2004 Bader Award LectureMetal-ion-catalyzed acyl and phosphoryl transfer reactions to alcohols: La3+-promoted alcoholysis of activated amides, carboxylate esters, and neutral organophosphorus esters

Unlike metal-ion-catalyzed hydrolysis processes, metal-ion-catalyzed methanolysis processes have received scant attention in the literature particularly from the standpoint of mechanistic studies. La3+, introduced into methanol solution as its triflate or perchlorate salt, is particularly effective in promoting methanolysis reactions of unactivated and activated esters, phosphate triesters, and activated amides such as acetyl imidazoles and lactams. Studies of the kinetics of methanolysis of these substrates as a function of solution pH and [La3+] indicate that the solution comprises lanthanum dimers with one to five associated methoxides (La23+(–OCH3)1–5), the most catalytically active form being La23+(–OCH3)2, which is produced at near neutral pH in methanol (8.4). Mechanisms for all the acyl and phosphoryl transfer reactions are proposed where the metal ion serves a dual role of acting as a Lewis acid to activate the C=O or P=O system to nucleophilic attack by a metal-coordinated methoxide nucleophile. In cases where direct comparisons can be made, the La23+ catalyst system is more active for the methanolysis of nonactivated substrates than for activated substrates. Another general characteristic of this system is that the catalytic rate constant for the metal complex exceeds the second-order rate constant for free methoxide, in some cases by as much as 4600-fold. Overall the catalytic effects exhibited by the La23+ system is spectacular for such substrates as paraoxon, where as little as 2 mmol L–1 La(OTf)3 in the presence of equimolar NaOCH3 accelerates the methanolysis by 109-fold relative to the background reaction at neutral pH and ambient temperature.Key words: kinetics of methanolysis, metal ion catalysis, lanthanides, methanolysis of carboxylate esters and phosphate esters.

On the magnitude and specificity of medium effects in enzyme-like catalysts for proton transfer.

Medium effects are normally studied by comparing the rates of reactions in different solvents. However, medium effects at the active site of enzymes differ dramatically from bulk solvents, both in their diversity (the presence of more than one type of "solvent") and in their spatial arrangement. We describe medium effects in a simple catalytic system, obtained by systematic alkylation of a polymeric scaffold bearing amine groups to give synzymes that catalyze the Kemp elimination of benzisoxazoles with remarkable efficiency. Our analysis indicates that catalysis by these synzymes is driven primarily by specific, localized enzyme-like medium effects, and these effects seem to differ dramatically from the nonspecific medium effects (i.e., desolvation activation) exhibited by solvents. Ligand-binding studies indicate that the synzyme active sites provide localized microenvironments affording a combination of hydrophobic and apolar regions on one hand and dipolar, protic, and positively charged on the other. Such localized microenvironments are not available in bulk solvents. A Brønsted (leaving group) analysis indicates that, in comparison to solvent catalysis, the efficiency of synzyme catalysis shows little sensitivity to leaving group pK(a). We show that enzyme-like medium effects alone, in the absence of efficient positioning of the catalytic amine base relative to the substrate, can give rise to rate accelerations as high as 10(5), for both activated and nonactivated substrates. Supported by the accidental identification of active sites on the surfaces of noncatalytic proteins and the promiscuous activities found in many enzymes, our findings suggest that the interfaces of protein surfaces and their hydrophobic cores provide a microenvironment that is intrinsically active and may serve as a basis for further evolutionary improvements to give proficient and selective enzymes.

Substrate specificity of lipase B from Candida antarctica in the synthesis of arylaliphatic glycolipids

Arylaliphatic glycolipids are known for their pharmaceutical and medicinal properties. We found that a great variety of arylaliphatic esters can be synthesized from non-activated substrates like glucose or the natural occurring drug salicin using lipase B from Candida antarctica (CAL-B). However, esters based on aromatic carboxylic acids or unsaturated arylaliphatic acids, like cinnamic acid and its derivatives, which are known to display anticancer activity, could not be obtained. In this work, we performed computer-aided molecular modeling based on data of our work published recently and syntheses of new glycolipids to understand why some substances are accepted by CAL-B while some are not. For this purpose, we investigated the accessibility of the lipase binding site for the arylaliphatic acyl donors as well as the steric interactions between the aglycons of glucosides and the residues of the alcohol binding pocket in order to elucidate potentials and limitations of CAL-B for the synthesis of aromatic glycolipids.

First palladium-catalyzed Heck reactions with efficient colloidal catalyst systems

For the first time it has been shown that palladium colloids are effective and active catalysts for the olefination of aryl bromides (Heck reaction). Worthy of note are the high activities of the catalyst system for activated aryl bromides under optimized reaction conditions, which are better than or comparable with “classical” palladium phosphine complexes. Addition of phosphines strongly retards the reaction rate of the colloid catalyst. Nevertheless, this type of catalyst is not suitable for the activation of non-activated substrates, especially technically interesting aryl chlorides.

Zum mechanismus der heck-reaktion: Katalysator-deaktivierung durch PC-bindungsbruch

The conventional palladium catalysts used in Heck reactions —Pd(OAc)2 + n P(aryl)3—suffer from extensive PC-bond cleavage at temperatures that would be necessary to activate aryl chlorides and electron-rich aryl bromides (> 120°C). This type of catalysts is, thus,not suitable to perform Heck reactions with non-activated substrates, especially with the technically interesting aryl chlorides.

Trans: cis Olefin ratios in the elimination reactions of 1-benzylethyl halides and toluene-p-sulphonate in different base–solvent systems

trans:cis Olefin ratios have been determined for the elimination reactions of 1-benzylethyl halides and tosylate PhCH2CHXMe (X = Br, I, or OTs) in different base–solvent systems. The trans : cis ratio is substantially the same for X = Br and I, whereas a lower value is observed for X = OTs. The basicity of the nuclecphile does not appear significantly to affect the trans : cis ratio. However, an increase in this ratio is observed in going from a protic to a dipolar aprotic solvent and from EtONa–EtOH to ButOK–ButOH. Ion association increases the trans : cis ratio when X = I and Br. whereas it has practically no effect on the geometrical orientation when X = OTs. The present results are discussed by comparison with those obtained in the corresponding reactions of non-activated substrates.